areaprescribing$committee$meeting$ - …€¦ · · 2013-10-28minutes of the meeting of the...

AREA PRESCRIBING COMMITTEE MEETING THURSDAY 7th FEBRUARY 2013

2pm CONFERENCE ROOM, BEACON UNIT, PENRITH HOSPITAL

AGENDA

1. APOLOGIES FOR ABSENCE

2. DECLARATION OF INTEREST

3. MINUTES OF PREVIOUS MEETING -‐ held 6th December 2012

3

4. MATTERS ARISING and ACTION PLAN 10 • Letter from J Howarth 17 • Riluzole SCP 18

5. LOTHIAN JOINT FORMULARY 5.1 Recent new drug recommendations TS To follow 5.2 Amendments – November 2012 TS 21 5.3 Amendments – December 2012 TS 23

6. CONTRACT MONITORING

6.1 Antibiotic formulary compliance WG, PB

6.2 NSAID prescribing WG, PB

6.3 Medicines reconciliation WG, PB

6.4 Antimicrobial stewardship WG, PB

7. NICE GUIDANCE 7.1 NICE Technology Appraisals TS 24

8. CLINICAL MATTERS 8.1 Fingolimod position statement and prior approval AL 25 8.2 NETAG – Aflibercept for AMD AL, TS 27 8.3 NETAG – Antithymocytic globulin AL, TS 28

8.4 Metolazone AL, TS 29 8.5 Ferrinject® HH 30 8.6 Guidelines for the treatement of non-‐cancer pain AL 32 8.7 Treatment of bronchiectasis AL 42 (UHMB guidelines

to follow)

9. OPERATIONAL

9.1 Discharges from NCUH WG, AL

44

9.2 Developing local formularies AL 47 9.3 NETAG proposal AL 59

10. DRUG SAFETY

10.1 Drug Safety Update – December 2012 All 62 10.2 Drug Safety Update – January 2013 All 70

12. MINUTES RECEIVED (for information) 12.1 UHMB D&TG (3rd December) 79 12.2 Lancashire Medicines Management Board (11th

November) 83

12.3 Lancashire Medicines Management Board (13th December) 94 12.4 Lothian Joint Formulary (19th December) 102 12.5 North Lancs Joint Area Prescribing and Medicines

Optimisation Group (12th December) 112

13. ANY OTHER BUSINESS

14. DATE OF NEXT MEETING To be arranged

APC MINUTES

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PRESENT: Andrea Loudon, Head of Medicines Management, NHS Cumbria (Chair)

Catherine Bousfield, Local Pharmaceutical Committee Representative Helen Huck, Lead Pharmacist, Cumbria Partnership Foundation NHS Trust Dr Andrea Mulgrew, GP Prescribing Lead, Allerdale Locality, Cumbria CCG Sarah Roberts, Patient Voice Group Representative Tim Slaughter, Clinical Effectiveness Pharmacist, NHS Cumbria Dr Julia Smith, GP Prescribing Lead, South Lakeland Locality, Cumbria CCG Dr Peter Weeks, Local Medical Committee Representative

In attendance, for item 8.10 Dr Ron Siddle Dr John Howarth 66/12 APOLOGIES FOR ABSENCE

Apologies for absence were received from: Bill Glendinning Dr Amanda Pugh Ros Berry Pauline Bourne

ACTION

67/12 DECLARATION OF INTERESTS None

68/12 MINUTES OF THE PREVIOUS MEETING The minutes of the previous meeting held on 11th October 2012 were agreed.

69/12 69/12/01

MATTERS ARISING See Action List for progress from previous meetings. Main Actions - NICE headache guidance (CG150) – NICE bites It was agreed that the table on recommended treatments from NICE Bites, October 2012 would be added to Prescription Pad. It was noted that topiramate was ‘off label’ for under 18yrs. GPs agreed that they would not

TS (PP)

MINUTES OF THE MEETING OF THE CUMBRIA AREA PRESCRIBING COMMITTEE HELD ON THURSDAY 6th December 2012

2.00PM, Beacon Unit Penrith Hospital

APC MINUTES

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69/12/02 69/12/03 69/12/04

prescribe unless under specialist advice. GREEN for > 18yrs and AMBER for <18yrs NOACs patient leaflet The patient information leaflet from South London Cardiac and Stroke Network was agreed to be a useful resource. It needs to be adapted for local use and notification of availability included in Prescription Pad. Paliperidone Although paliperidone is more expensive than risperidone, it has benefits in that it needs to be administered less frequently (4 weekly instead of 2 weekly) and it has no cold-chain requirements for storage. Melatonin It was agreed that HH could develop a SCG for melatonin that recommended using branded formulations of melatonin, either Circadin® or Bio-melatonin®. The use of these preparations will give more consistency of the formulations used. It was agreed that GPs should continue prescribing if they have already agreed to do so.

TS (PP)

70/12 70/12/01 70/12/02 70/12/03 70/12/04 70/12/05 70/12/06

LOTHIAN JOIN FORMULARY Recent new drug recommendations (Oct 2012) Eplenerone - addition to standard optimal therapy, to reduce risk of cardiovascular mortality and morbidity in adult patients. Included in LJF as a prescribing note for treatment of NYHA class II patients only, subject to clarification of patient numbers. Estimated potential eligibility of 128 per 100,000 patients (cost approx £355k a year). AMBER Colecalciferol (Futium-D3®) - for prevention and treatment of vitamin D deficiency in the elderly, adults and adolescents, and as an adjunct to specific therapy for osteoporosis in patients with deficiency or at risk of insufficiency. Included in LJF for the indication in question. GREEN. Colecalciferol (Dekristol®) - Treatment of vitamin D deficiency. Added to LJF for general use. GREEN Fidaxomicin - for treatment of adults with C Difficile infections. Included in LJF for indication in question, specialist use only. GREEN, but only after recommendation from microbiologist or gastroenterologist. Protocol for prescribing to be requested from microbiologist. Strontium ranelate - treatment of osteoporosis in men at increased risk of fracture. Not recommended due to non-submission. BLACK Zonisamide - monotherapy treatment for partial seizures (with or without secondary generalisation) in adults with newly diagnosed epilepsy (previously licensed as ‘add-on’ therapy). Not recommended due to non-submission.

TS

APC MINUTES

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70/12/07 70/12/08 70/12/09 70/12/10 70/12/11 70/12/12

BLACK Fluticasone + Salmeterol (Flutiform®) - in regular treatment of asthma where use of combination product is appropriate – for patients not adequately controlled on an inhaled corticosteroid (ICS) and ‘prn’ inhaled short-acting β2 agonist (LABA) or for patients already adequately controlled on both an ICS and a LABA. Included in LJF for the indication in question, suitable for prescribing where fluticasone, formoterol and a MDI are suitable. GREEN Ivabradine - for CHF (NYHA) II to IV class with systolic dysfunction. Added to LJF for patients with heart rate > 75 bpm. This recommendation has now been superseded by NICE TA267 (Nov 2012). AMBER TS to update the RAG and PBRe drug list. Summary of LJF Amendments received for October 2012 Gastrointestinal - Previously where esomeprazole would be appropriate, prescribers were encouraged to prescribe esomeprazole capsules rather than tablets, as they were cheaper. The tablets have now been added to the drug tariff, therefore there is no longer this requirement. CVS - Following a formulary application for the use of eplerenone in NHYA class II hear failure, the section has been amended. Spironolactone remains the aldosterone antagonist of choice for NHYA class III/IV heart failure. CNS - The section was updated to reflect the maximum recommended daily dose of 40mg citalopram. Information on dose dependent QT interval prolongation has also been included. Obstetrics & Gynaecology - The section was updated to include information on the treatment of erectile failure patients with severe distress. LJF decisions to be added or amended on the PBRe and RAG lists. Updates to be included in PPad.

TS (PP) TS (PP)

71/12 71/12/01

CONTRACT MONITORING i) Antibiotic formulary compliance ii) NSAID prescribing iii) Medicines reconciliation iv) Antimicrobial stewardship Due to absence of PB and BG unable to discuss this item.

72/12 72/12/01

NICE GUIDANCE NICE Technology Appraisals TA265 Denosumab - recommended as an option for preventing skeletal-related events in adults with bone metastases from breast cancer. and from

APC MINUTES

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solid tumours other than prostate if:

bisphosphonates would otherwise be prescribed and

the manufacturer provides denosumab with the discount agreed in the PAS.

NICE costing template anticipates this will be given solely in secondary care, therefore assigned RED. Noted that Denosumab is not PBR excluded therefore hospital spend is within PBR Tariff. Overall implementation costs would be £166k per year. List price for denosumab is £310, PAS price is £220. TA266 Mannitol dry powder - recommended as an option in the treatment of cystic fibrosis in adults who cannot use dornase-α because of ineligibility, intolerance or inadequate response and whose lung function is rapidly declining and for whom other osmotic agents are not considered appropriate. National population eligible for treatment is about 300. Cost per patient per year is about £6k, same cost as dornase-α, so cost impact considered to be small. TA267 Ivabradine - recommended as an option for treating congestive heart failure. Only to be initiated after a stabilisation period of 4 weeks on optimised standard therapy with ACE inhibitors, ß-blockers and aldosterone antagonists. Should be initiated by HF specialist with access to multi-disciplinary HF team. Dose titration and monitoring should be carried out by a HF specialist or in primary care by either GPSI or HF specialist nurse. NICE calculates that drug and initiation costs will be £91k per annum. Cost savings on fewer hospital admissions mean that total extra cost will be about £23k per annum. AMBER with monitoring by HF specialist nurse

TS (PP)

73/12 73/12/01 73/12/02 73/12/03

OTHER CLINICAL MATTERS Antibiotic guidelines – for approval The antibiotic guidelines for primary care were tabled for approval. It was noted that the treatment duration for many indications has been reduced and that this should be noted in Prescription Pad. AL agreed to circulate to Eric Rooney (Public Health Dental Consultant). PW agreed to post the guidelines on the LMC website. Exenatide and liraglutide treatment agreement The patient agreements from NHS Northampton were discussed. There was some questioning as to whether the need for exenatide and liraglutide should still be classified as AMBER drugs in Cumbria, while many other areas listed them as GREEN. It was agreed that the classification should be discussed with Dr. Hay before considering the patient agreement forms further. Guidance for converting between opioids – for approval A conversion chart for changing from opiate patches (fentanyl and buprenorphine) to oral agents. These were approved. To be put on website

TS (PP) AL/TS

APC MINUTES

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73/12/04 73/12/05 73/12/06 73/12/07 73/12/08 73/12/09 73/12/10

and highlighted in Prescription Pad. NETAG – bevacizumab for hereditary haemorrhagic telangiectasia This was noted for future reference. NETAG – perampanel for focal epilepsy This was noted for future reference. Pregabalin or gabapentin for neuropathic pain – for approval The detail aid on the use of gabapentin and pregabalin in the treatment of neuropathic pain were discussed and approved. It was noted that considerable savings could be made if gabapentin was used instead of pregabalin. Antipsychotics and dementia audit It was noted that % patients with dementia prescribed an anti-psychotic had decreased to 16.6% at August 2012 compared to 18% at August 2011. The Banerjee report published in 2009 called for a reduction of a third year on year. National audit figures from just under 50% of GP practices report 7% in 2011. The NW average was 12%. Cumbria therefore still has a significant number of patients with dementia prescribed antipsychotics. The number is expected to decrease as GP practices review their prescribing as part of the QOF MM 6-10 indicators. Riluzole shared care protocol – for approval Amendments to be made to ensure that first year of tests, prescribing and monitoring are the responsibility of secondary care. AL to add riluzole to NPT LES for annual blood monitoring - AL to check with PRIMIS team that practices will only receive a quarter payment. Post script: riluzole is listed as a PBR excluded drug to be commissioned by the NHSCB from April 2013. Riluzole, therefore, to remain RED. SCG not required. Fesoterodine formulary application Mr Jain (Consultant Urologist, UHMB) submitted a request for Fesoterodine to be included on the formulary. After discussion, it was agreed that it did not have any significant benefit over the present formulary choices, oxybutynin and solifenacin. (Since the meeting, LJF turned a request for formulary inclusion) Antipsychotic audit in South Cumbria (this was discussed at the beginning of the meeting with Ron Siddle and John Howarth present). The audit of antipsychotic prescribing carried out in August identified a

TS (PP) TS (PP) TS/AL

APC MINUTES

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significant number of patients being prescribed atypical antipsychotics for indications outside both the license and the shared care protocol. This was highlighting concerns the GPs had about the expectation that they would assume responsibility for the physical welfare of these patients and that there was potential for patients slipping through the system in the expectation that this care was being provided by other healthcare staff. John Haworth and Peter Weeks agreed to write to commissioners seeking development of a Local Enhanced Service for physical and mental health monitoring. It was agreed that amendments to the SCG would await the outcome of the above discussions.

PW

74/12 74/12/01 74/12/02 74/12/03

OPERATIONAL High cost medicines and NHS Commissioning Board Major changes in NHS commissioning arrangements will have significant impact on how many high-cost, tariff excluded medicines, are commissioned and funded. Prescribed Specialist Services The draft list of these services that will be directly commissioned by the NHSCB from 1st April 2013. The NHSCB specialist commissioning directorate require estimated spend on PBRe drugs based on M6 figures. Likewise for PBRe drugs prescribed by GPs and those paid for directly by PCT to homecare companies. Suggested commissioning intentions 13/14 Paper circulated for information. AL was not able to report if any of the suggestions had been agreed with provider organisations.

75/12 75/12/01 75/12/02

DRUG SAFETY Drug Safety Update – October 2012. Received for information. It was agreed that it would be useful to highlight the diclofenac information in the next Prescription Pad. Drug Safety Update – November 2012. Received for information.

TS (PP)

76/12 76/12/01

FOR INFORMATION Insulin passport GPs reported that they had not seen this correspondence. Request that this information is disseminated again via MM network.

77/12

MINUTES RECEIVED (for information) NECDAG (26th September) NCUHT D&T Committee (17th September)

APC MINUTES

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Blackpool & NL Area Medicines Optimisation Group (24th October) Lancashire Medicines Management Board (4th October) Lothian Joint Formulary (3rd October) Lothian Joint Formulary (14th November)

78/12 ANY OTHER BUSINESS i) Guidelines for prescribers in primary care: Prescribing infant

formula in cows’ milk protein allergy and lactose intolerance - for approval approved on the condition that GPs are not required to issue the first prescription for lactose-free milks. Unless the parent/guardian is in receipt of milk tokens as they do not cover the cost.

ii) North of England Cardiovascular Network: Antiplatelet therapy for STEMI – for information it was noted that the guidance differed for NSTEMI PCI from South Cumbria and Lancashire Cardiac Network. To be shared with GPs via PP highlighting the difference as they may have patients who present for PCI at a North East centre.

iii) Powerbreathe – for formulary approval. Not approved due to lack of supporting clinical and cost-effectiveness data.

79/12 DATE and TIME of next meeting Dates to be confirmed

AREA PRESCRIBING COMMITTEE ACTION LIST

2012

Page 1 of 7

Agenda Item Reference

Details of Action Agreed Action

by whom

Target Date

Progress

10/10/01 Melatonin shared care protocol 14/4/11 AL & HH to produce pathway for melatonin prescribing with local prescribers. BG to ensure that patients for Cumbria Partnership liaise with HH to get FP10 pad. 11/10/12 BG to share link for NICE unlicensed medicines review as Melatonin is listed

HH

BG

Aug 11

Dec 12

In progress 14.6.12 HH drafted report for children’s services and is trying to access ePACT data (TS). To recommend 1st & 2nd line preparations. COMPLETED

30/11/01 Formulary Compliance 3/12/01 AL to check Scriptswitch 59/12/04 HH to advise consultants to prescribe Venlafaxine IR rather than MR preparations. TS to insert paragraph on NICE guidance & cost comparison for circulation to GPs.

AL

HH TS

Dec 12

Dec 12 Dec 12

COMPLETED COMPLETED COMPLETED


2012

Page 2 of 7

36/11/04 Keeping patients safe when transferring between care providers – getting the medicines right RPS July 2011

Check the content of their Trusts discharge summary and determine if there are any gaps. AL to look at why Blackpool cardiologists discharge sheets routinely state ‘ no changes to medicines’ when clearly there are. 11.10.12 AP and JS to provide AL with examples, to share with Cardiac Network.

AL

AP JS

Jun 12

Dec 12

51/11/01 Lancashire Priority Setting of Medicines – 2.2 AL waiting for RB to complete Ethical Framework. Still to go to D&T Committees for ratification.

AL,

BG, PB

Dec 11

On hold due to organisational change. Deferred

07/12/05 Implementation of BlueTeq TS to provide training to clinical staff

TS

Oct 12

COMPLETED

17/12/02 Homecare national benchmark audit BG to share when completed 11.10.12 BG to bring audit results to December meeting

BG

Aug 12

COMPLETED

19/12/02 Paliperidone depot injection – HH to share criteria for use document. 55/12/02 CPT D&T discussed, wording of criteria being finalised.

HH

HH

June 12

COMPLETED


2012

Page 3 of 7

22/12 NICE Guidance TA249 Dabigatran 59/12/02 AL to bring decision aid to Dec meeting.

AL

Dec 12

COMPLETED

32/12/02 Prescribing of ibuprofen & naproxen as a proportion of all NSAID prescribing 11.10.12 HH to send relevant indicators to AL.

HH

Dec 12

Not required.

32/12/03 Medicines Reconciliation PB and BG to audit 11.10.12 To audit quarterly

BG. PB

Aug 12

32/12/04 Antimicrobial Stewardship Action Plan 11.10.12 BG & PB to feedback to contract monitoring dept difficulties in obtaining data, needs to be in place by Dec to avoid penalties.

BG, PB

Aug 12

34/12/07 Vitamin D, choice of preparations 55/12/01 TS to add link and treatment recommendations to PPad.

TS

Dec 12

37/12 Pharmaceutical Industry sponsorship Pharmaceutical Industry Policy: AM to bring draft policy to next meeting 11.10.12 CCG may be developing policy.

AM

Aug 12


2012

Page 4 of 7

43/12/07 Azithromycin dehydrate TS to amend and update PBRe & RAG lists and add to PPad.

TS

Oct 12

COMPLETED

45/12 NICE GUIDANCE CG140 Opioids in palliative care 11.10.12 JM summarised guidance - no significant changes to current practice. Morphine remains first choice. Patches only if oral route not available (lowest acquisition cost). Butrans blacklight in Cumbria. TS to review costs of transdermal patches. TS to summarise for PP

TS

TS

Oct 12

Dec 12

COMPLETED

47/12/03 Dementia Guidelines To send to Dementia Strategy Group. 64/12 (11.10) Draft Protocol, scrutiny tool and record form brought to meeting. HH to send to Jim George (North Cumbria) and Paul Atkinson (South Cumbria) for information.

HH

HH

Oct 12

Dec 12

COMPLETED COMPLETED

48/12/01 Drug Safety Update June 12 Oral Tacrolimus products – TS to look at prescribing breakdown by locality. To add reminder to PPad.

TS

Oct 12

56/12 56/12/02 56/12/04

LOTHIAN Joint Formulary decisions Aug12 TS to update RAG and PBRe list Tobramycin Need to consider fit with Specialist commissioning Eplerenone TS to clarify traffic lighting.

TS

RB TS

Dec 12

Dec 12 Dec 12


2012

Page 5 of 7

56/12/09 56/12/11 56/12/12 56/12/13

LJF summary of amendments July and Aug 2012 LJF decisions to be added/amended to PBRe and RAG lists and noted in PP. Exanatide/liraglutide monitoring forms to be produced by Cumbria Diabetes. Gonadorelin analogues to be prescribed generically – AL to let BG know which consultants in NC prescribing by Zoladex Brand. Wound Formulary – Wound Management Group to be re-formed.

TS

AL

AL

HH

Dec 12

Dec 12

Dec 12

Dec 12

59/12/03 Flutter device formulary request TS to inform the applicant and include decision and rationale in PP.

TS

Dec 12

COMPLETED

59/12/05 Lithium guidelines TS to add reminder in PPad to GPs on use of purple monitoring booklets and link to guidelines. JF to add piece in Community Pharmacy Newsletter reminding pharmacists to ask to see booklet, reinforcing that patient needs to bring the booklet with them. TS to look at epact to see if brand name prescribing is being adhered to.

TS JF

TS

Dec 12

COMPLETED COMPLETED

59/12/06 Prescribing of non-drug items (excluding dressings) TS to look at amount and cost of items

TS

Dec 12

60/12/08 Innovation Health & Wealth TS to add a rider to the LJF link on the website.

TS

Dec 12

60/12/09 NICE TA adherence checklist TS to complete for APC

TS

ONGOING


2012

Page 6 of 7

61/12/01 Drug Safety Update Aug 12 Item on Simvastatin drug interactions and contraindications for PPad.

TS

Dec 12

COMPLETED

69/12/01 NICE Guidelines Add headache treatment table to Prescription Pad

TS

Feb 13

69/12/02 NOACs leaflet Adapt South London Cardiac and Stroke Network leaflet for local use

TS

Feb 13

69/12/04 Melatonin Develop SCG for melatonin, recommending use of Circadin or Biomelatonin

HH

Feb 13

70/12/04 Fidaxomicin Obtain protocol for appropriate use from microbiologists

TS

Feb 13

70/12 New drugs Update the RAG and PBRe drug list.

TS

Feb 13

70/12 Updates to LJF Highlight changes in PP

TS

Feb 13

72/12 NICE guidance Insert recommendations in PP and RAG list

TS

Feb 13

73/12 Antibiotic guidelines TS to send copies to Eric Rooney, Peter Weeks. Circulate via PP and post on website

TS

Feb 13


2012

Page 7 of 7

73/12/02 Exenatide and liraglutide Discuss RAG classification with Dr Hay

TS/AL

Feb 13

73/12/03 Guidance for converting between opioids To add to website and PPad.

TS

Feb 13

73/12/06 Pregabalin and gabapentin Circulate via PP

TS

Feb 13

73/12/08 Riluzole Make changes to SCP so that first year monitoring is done in secondary care Add to NPT LES

TS

AL

Feb 13

Feb 13

73/12/10 Antipsychotic audit in South Cumbria PW and John Howarth to write to commissioners to develop LES for physical and mental health monitoring

PW/JH

Feb 13

75/12 Drug Safety Update Include DSU information in next PP

TS

Feb 13

78/12 Powerbeathe Include recommendation in PP

TS

Feb 13

Voreda Learning Network and Trust HQ

Portland Place PENRITH

CA11 7QQ Tel No: (01228) 60 8398

Direct Line: (01228) 60 8372 Fax No: (01228) 60 2550

8 January 2013 Email: [email protected] Attention: Dr Jim Hacking Dr Rachel Preston Laura Carr Dear Jim, Rachel and Laura, Re: Improving physical health for mental health - aligning incentives to focus on the first year after diagnosis At the area prescribing committee last month the LMC representative Dr Peter Weeks expressed concern about GPs having to monitor the physical aspects of anti-psychotic use for patients with enduring mental health issues in the first year after diagnosis without associated payment. The LMC point out that in other areas such as anti-coagulation there is specific payment for the service. The particular issue comes in the first year of prescribing (i.e. before the first annual review when it becomes part of the QOF). In the first year of starting an antipsychotic the current agreement states that the primary responsibility for monitoring lies with the specialist but when the specialist does not have the capacity in his clinic to do the physical health monitoring he can ask primary care to do this. The agreement states that after the first year the responsibility passes to primary care. I have real concerns that some patients will fall through the gap here and not enough priority is given to the first year which is probably the main window of opportunity to prevent physical ill health. How we jointly manage the first psychotic episode is crucially important. Most of the weight gain (14kg on average) comes during the first year of starting an antipsychotic. We need an intensive wellness offer alongside our biomedical offer in the first year to try and avoid the development of metabolic syndrome and promote self care and recovery. This will need very close partnership working between specialist services, primary care and the Third sector. I think we need a massive push on this and would welcome a discussion on aligning incentives – i.e. CQUIN for CPFT next year and a possible LES for primary care both focussed on the first year after diagnosis. Could we meet to discuss this further? Regards, John Dr John Howarth Director of Integration cc Ron Siddle Andrea Louden Dr Peter Weeks LMC

Date Prepared: August 2012 Date of Review: July 2013

S H A R E D C A R E G U I D E L I N E Drug: RILUZOLE

Contact Details Name: _____________________________

Location: __________________________

Date: ______________________________

Tel ( : ____________________________

Patient ID Label Surname: __________________________

Forename/s: ________________________

NHS Number: _______________________

Date of Birth: _______________________

Introduction Indication:

To extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis (ALS).

Safety and efficacy of riluzole has only been studied in ALS. Therefore, riluzole should not be used in patients with any other form of motor neurone disease.

Riluzole should only be initiated by a neurological specialist with expertise in the management of motor neurone disease (MND) (as per NICE TA 20, 2001).

Background: ALS is the most common variant of MND accounting for 65% to 85% of all cases. It is a progressive, fatal neurodegenerative disorder with a median survival of 37 to 49 months. It is characterised by progressive deterioration of muscle tissue (amylotrophy), resulting in both upper and lower motor neurone signs.

Death usually results from ventilatory failure, resulting from progressive weakness and wasting of respiratory and bulbar muscles within approximately 3 years of the onset of symptoms.

Although the pathogenesis of ALS is not completely elucidated, it is hypothesised that excessive stimulation of glutamate receptors on neurones may cause or play an important role in the destruction of motor neurones in MND.

In vitro, riluzole inhibits the release of glutamate; decreases firing of motor neurones induced by glutamate receptor agonists and thus protects cells from glutamate-mediated damage.

Riluzole is the only drug currently licensed for the treatment of ALS however symptomatic management, supportive, and palliative care are also available for patients with ALS.

Dose & Administration

The recommended dose is 50mg twice daily.

Tablets should be taken 12 hours apart, on an empty stomach (1hour before or 2 hours after food).

If there are problems swallowing, the tablets may be crushed and mixed with a teaspoon of sugar to aid swallowing (off label use).However, when crushed, the drug can produce a temporary numbing effect in the mouth. It may be easier to swallow if crushed and mixed with a soft food product such as a puree, yoghurt, ice cream or a thick beverage and eaten in the usual way. Once it is crushed it should be taken immediately due to limited stability problems.

Patients should be aware that they will not experience any subjective benefit from taking the medication and may experience unwanted side effects.

Secondary Care Responsibilities

1. Confirm the diagnosis of MND.

2. Assess the need for and appropriateness of riluzole.


3. Discuss the benefits and side effects of treatment with the patient.

4. Perform pre-treatment screening (full blood count and serum transaminases).

5. Prescribe and monitor riluzole for at least twelve months to establish efficacy and safety (FBC (including differential WBC), U&E and LFT (incl ALT) monthly for the first three months of treatment and then 3 monthly for the rest of the year).

6. Arrange shared care with the patient’s GP.

7. Review the patient regularly to monitor the patient’s response to therapy.

8. Request copies of test results for the patient’s GP by completing the “copy to” section on the pathology form.

9. Advise patients or their carers how to recognise signs of neutropenia and advise them to seek immediate medical attention if symptoms such as fever occur.

10. Ensure that clear backup arrangements exist for GPs to obtain advice.

11. Promptly inform the GP of any changes in treatment following hospital admission or out-patient consultation.

Primary Care Responsibilities

1. Provide the patient with prescriptions for riluzole 50mg tablets after the initial minimum three months treatment.

2. Monitor the patient’s overall health and well being and report signs of disease progression to the consultant or the specialist nurse.

3. Arrange ongoing monitoring at the recommended frequencies (see MONITORING below).

4. Request copies of test results for the patient’s consultant by completing the “copy to” section on the pathology form.

5. Report any adverse events to the consultant or specialist nurse and stop treatment on their advice or immediately if an urgent need arises.

6. Report any serious suspected adverse events to the MHRA.

7. Advise patients and their carers on how to recognise signs of neutropenia and to seek immediate medical attention if symptoms such as fever occur.

8. Report any febrile illness to the specialist team and check the white blood cell count.

9. Symptomatic management of minor adverse effects.

Monitoring Required in Primary Care

After the initial minimum three months prescribed by secondary care:

• FBC (including differential WBC) and LFTs every three months for a further nine months then repeat annually

Discontinue riluzole and seek advice if:

• ALT levels increase to five times the upper limit of normal range (≥ 225 IU/L)

• There is evidence of neutropenia

Adverse Effects The most common side effects are:

• Gastrointestinal upsets including nausea, anorexia, constipation, diarrhoea

• Tiredness and fatigue (asthenia)

• Headache, dizziness, somnolence (patients should be warned about not driving or operating machinery if affected)

• Tachycardia

• Elevation of ALT levels

It is estimated that approximately 10% of patients are likely to experience side effects of


such intensity that they consider discontinuing the drug.

Anaphylactoid reaction, angio-oedema, neutropenia and pancreatitis have been reported rarely

If respiratory symptoms develop e.g., dry cough and/or dyspnoea, chest radiography should be performed, and in case of findings suggestive of interstitial lung disease (e.g., bilateral diffuse lung opacities), riluzole should be discontinued immediately.

Any reports of febrile illness should result in discontinuation of riluzole and differential FBC to assess for neutropenia

Patients should be warned about the potential for dizziness or vertigo, and advised not to drive or operate machinery if these symptoms occur

Always consult the latest version of the Summary of Product Characteristics (SPC) at www.medicines.org.uk for full details

Common Drug Interactions

There have been no clinical studies to evaluate the interactions of riluzole with other medicinal products.

However, as riluzole is metabolised by the liver, there is a possibility that it may interact with:

• CYP1A2 inhibitors that may potentially decrease the rate of riluzole eliminations e.g. diclofenac, diazepam, clomipramine, imipramine, theophylline, amitriptyline and quinolones

• CYP1A2 Inducers that could increase the rate of riluzole elimination e.g. cigarette smoke, charcoal broiled food, rifampicin and omeprazole.

Contra-indications • Previous history of liver disease or if their baseline ALT/AST levels are greater than three times the upper limit of normal

• Impaired renal function

• Previous allergic reaction to riluzole

• Neutropenia

• Signs of dementia and/or major psychiatric disorders

• May be pregnant or are breastfeeding

• Unlikely to comply with the requirements of treatment i.e., blood tests

This guidance does not replace the SPC, which should be read in conjunction with this guidance.

Prepared December 2012 – JP

Summary of Lothian Joint Formulary Amendments The purpose of this summary is to detail the main changes to the LJF

sections and provide additional information on the reasons for some of the changes.

The website should be referred to for full details of all the changes. The month indicates when Formulary Committee approved the changes.

November 2012

Chapter 2 Cardiovascular – Adult

2.6.3 Other anti-anginal drugs

• Following approval at Formulary Committee for the use of ivabradine in heart failure NHYA class II to IV, the section has been updated. It includes details on patient eligibility and dosing.

Chapter 6 Endocrine – Adult

6.1.2 antidiabetes drugs c) other antidiabetes drugs

(i) dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitors)

• There has been recent MHRA advice about the increased risk of

pancreatitis with gliptins. A prescribing note has been added to provide some more detail about this.

• The licence for sitagliptin has changed it now includes information on use in patients with renal impairment. The dosing section in the

LJF has been updated with this information. • Previously saxagliptin was included as a prescribing note, for use in

patients with renal impairment, as it was the only product licensed.

The prescribing note has been removed. Although saxagliptin is approved for use in a specific indication by the SMC, it is not

preferred in Lothian. • Sitagliptin has a wider range of SMC approved indications, therefore

is more suitable for use in NHS Lothian.


Chapter 13 Skin – Adult 13.5.2 Preparations for psoriasis

• The prescribing notes and choices box have been amended. • The choices box now includes information specifically on treating

face or flexures; and; trunk, limbs, scalp. • Prescribing notes have been updated to clarify the use of

combination products (topical corticosteroid and vitamin D analogue) in psoriasis.

Gluten Free -Adult

• Following a formulary amendment request gluten free cereal and

oats have been added to the formulary choices. • The choice of rolls has been amended to reflect the change in the

products available from the manufacturer.

• A new prescribing note has been added to note that all newly diagnosed patients should avoid oat products for 6-12 months, and

the reintroduction of oat products should follow the advice of a specialist clinician.


Summary of Lothian Joint Formulary Amendments The purpose of this summary is to detail the main changes to the LJF

sections and provide additional information on the reasons for some of the changes.

The website should be referred to for full details of all the changes. The month indicates when Formulary Committee approved the changes.

December 2012

Chapter 7 Obstetrics and Gynaecology – Adult

7.1 Drugs used in obstetrics Suppression of lactation

• Following approval at Formulary Committee, a prescribing note has

been added to the LJF regarding the specialist use of cabergoline

for the suppression of initiation of lactation in women with foetal loss after 24 weeks.

Wound Formulary (j) Orthopaedic wadding

• The first and second choice products have changed. This is due to

the removal of the existing products from the drug tariff. First choice is now Ultra Soft and second choice is K-Soft.

1

NICE Technology Appraisals Technology Assessment Drug Condition Type of

assessment Date of

Publication Summary of guidance Present LJF recommendation Cost implications for Cumbria

TA268 Ipilimumab Melanoma (stage III/IV)

Single December 2012

Recommended as an option for treating advanced (unresectable or metastatic) melanoma in people who have received prior therapy. Subject to PAS.

The submitting company's justification of the treatment's cost in relation to its health benefits was not sufficient and, in addition, the submitting company did not present a sufficiently robust economic case to gain acceptance by SMC (May 12).

Estimated 140 patients per year in England & Wales. List price is £75k per treatment. RED

TA269 Vemurafenib Melanoma (BRAF V600 mutation positive, unresectable metastatic)

Single December 2012

Recommended as an option. Subject to PAS.

The submitting company did not present a sufficiently robust economic analysis and in addition their justification of the treatment’s cost in relation to its health benefits was not sufficient to gain acceptance by SMC (September 2012).

NICE estimates that the cost of the drug will be £189k and delivery cost is £6k. There will be reduced cost for some patients who would have received dacarbazine. The total net cost is £241k. This estimate does not take account of the PAS. RED

TA270 Decitabine Leukaemia (acute, myeloid)

N/A December 2012

No submission made to NICE. No submission made to SMC. BLACK

TA271 Flucinolone intravitreal implant

Diabetic macular oedema

Single January 2013

Not recommended (not cost effective).

SMC advice due in May 2013. BLACK

TA272 Vinflunine Urothelial tract carcinoma (transitional cell, advanced, metastatic)

Single January 2013

Not recommend for advanced or metastatic transitional cell cancer of the urothelial tract that has been treated previously with platinum-‐containing cancer drugs. The Committee considered that the clinical effectiveness of vinflunine compared with best supportive care had not been conclusively demonstrated.

The manufacturer's justification of the treatment's cost in relation to its health benefits was not sufficient and in addition, the manufacturer did not present a sufficiently robust economic analysis to gain acceptance by SMC.

BLACK

TA273 Tadalafil Benign prostatic hyperplasia

N/A January 2013

No submission made to NICE No submission made to SMC. BLACK

Acknowledgement: GMMMG Neuroscience Network – 9th May 2012 1

MEDICINES MANAGEMENT HEALTH ECONOMY NEW MEDICINES AND TREATMENTS GROUP

Fingolimod (Gilenya®) for the treatment of multiple sclerosis Introduction Multiple sclerosis is a disease in which areas of the brain and spinal cord become damaged by the body’s own immune system. In relapsing–remitting multiple sclerosis, people have flare-ups of symptoms (relapses) followed by a period of recovery (remission). Fingolimod (also known as Gilenya) stops white blood cells (part of the body’s immune system) from leaving the blood and entering the brain. This protects the brain and spinal cord from further damage by the white blood cells so that relapses of multiple sclerosis occur less often. Fingolimod is the first treatment for multiple sclerosis that is given in oral form. The NICE technology appraisal guidance (TAG) for Fingolimod was issued in April 2012. The East Lancashire New Medicines and Treatments Group considered the use of fingolimod (Gilenya®) for a sub-group of patients with multiple sclerosis (MS) in light of the NICE TAG (TA254):

POSITION STATEMENT Fingolimod is recommended as an option for the treatment of highly relapsing-remitting multiple sclerosis in adults meeting the following criteria:

• Patients who have rapidly evolving severe (RES) relapsing remitting MS but are not considered

suitable for natalizumab (Tysabri®

) because of the clinical concerns (risk stratification) about the possibility of developing progressive multifocal leukoencephalopathy (PML); or

• Patients who fail on natalizumab (Tysabri®

) due to neutralising antibodies and, or anaphylactic reaction; or

• Patients who fail on natalizumab (Tysabri®

) due to relapses; or • Patients who fail on beta-interferon (Avonex, Betaferon/Extavia, Rebif 22/44) and/or glatiramer

acetate (Copaxone®

) who have had more relapses than the previous year; or • Patients who fail on a beta-interferon (Avonex, Betaferon/Extavia, Rebif 22/44) and/or glatiramer

acetate (Copaxone®

) due to inability to self-inject, lack of adequate injection sites or skin necrosis; or • Patients who develop high and sustained levels of neutralising antibodies to a beta-interferon

(Avonex, Betaferon/Extavia or Rebif 22/44) and also fail on glatiramer acetate (Copaxone®

) due to inability to self-inject, lack of adequate injection sites or skin necrosis.

It is expected that the subgroup of patients using the drug is likely to be low and costs will be offset against the administration costs associated with natalizumab therapy. Fingolimod may cause transient bradycardia and therefore cardiac monitoring of patients due to risk of sudden death is required. Fingolimod is not recommended for patients with a history of cardiovascular or cerebrovascular disease or who take heart rate lowering medication. Patients will need to attend as an inpatient for monitoring, at the time of first dose. In addition, prescribing will be carefully monitored and audited in accordance with EMA, MHRA and SRFT guidelines. Fingolimod is recommended for use with the patient group defined above, and should only be initiated by consultant neurologists with a special interest in MS.

Lisa Rogan on Behalf of the ELHE New Medicines and Treatments Group Produced: October 2012 Review: October 2014

Trust:

Consultant making request:

Notification email address: (@NHS.net account ONLY)

Patient status: NHS ○ Private ○ GP/ Practice Code:

1

2

3

4

5

6

7

8

9

The patient does not have history of cardiovascular or cerebrovascular disease and is not taking heart lowering

medication.

Fingolimod will be supplied to the patient via Homecare with the discount agreed as part of the patient access scheme. Yes ○ No ○

Patient understands that they will be treated in line with NICE TAG254 and local policy, is aware and accepts criteria for

stopping treatmentYes ○ No ○

Yes ○ No ○

Patient is not considered suitable for natalizumab or has failed on natalizumab treatment

(Unsuitable because of the clinical concerns/ risk stratification about the possibility of developing progressive multifocal

leukoencephalopathy)

Yes ○ No ○

Yes ○ No ○

Patient has had previous treatment with either beta-interferon or glatiramer or both and has had an unchanged or

increased relapse rate or ongoing severe relapses compared with the previous year despite treatment

2012/13 PbR Exclusions - Funding Application for Fingolimod for rapidly evolving severe relapsing-remitting Multiple Sclerosis (NICE

TAG254)

Patient is currently not immunocompromised Yes ○ No ○

Patient has no signs of relevant treatment-related abnormalities e.g. neutropenia resulting from previous treatment with

beta interferon or glatiramer acetateYes ○ No ○

Patient is aged 18 - 65 years

Patient has a diagnosis of rapidly evolving severe relapsing-remitting multiple schlerosis (RES)

RES is defined by TWO or more disabling relapses in 1 year AND ONE or more gadolinium-enhancing lesions on brain

magnetic resonance imaging (MRi) or a significant increase in T2 leasion load compared with a previous MRI

Patient NHS No:

Patient Hospital No:

Patient DOB

Yes ○ No ○

Please indicate whether patient meets the following NICE criteria:

Yes ○ No ○

Please tick

http://www.google.co.uk/imgres?q=logo+nhs+lancashire&hl=en&sa=X&biw=1280&bih=568&tbm=isch&prmd=imvns&tbnid=qVdmoC7pKmbKeM:&imgrefurl=http://www.northlancshealth.nhs.uk/nlancs_info.asp%3FzoneID%3DCOR%26catID%3D1%26ID%3DCOR14&docid=wYV9n4NnoDWeSM&imgurl=http://filesdown.esecure.co.uk/NorthLancsPCT/NHS_Lancashire_Logo3.JPG_20092011-1356-48.JPG&w=158&h=78&ei=BVx8T8DgO6Wg0QX51I25DQ&zoom=1&iact=hc&vpx=134&vpy=203&dur=1406&hovh=62&hovw=126&tx=100&ty=20&sig=106863144102824205054&page=1&tbnh=62&tbnw=126&start=0&ndsp=21&ved=1t:429,r:0,s:0,i:6

Treatment Appraisal: Decision Summary

AFB-AMD-JAN13. Page 1 of 1

www.netag.nhs.uk

Date 15th January 2013

Appraisal Aflibercept (Eylea®) for neovascular age-related macular degeneration

Details The NHS North East Treatment Advisory Group was requested by the

North East Retinal Group to conduct an appraisal of and issue a

recommendation for the use of aflibercept within its licensed indication for the

treatment of neovascular (wet) age-related macular degeneration in advance

of a recommendation from NICE.

Recommendation The NHS North East Treatment Advisory Group recommends

aflibercept (Eylea®) within its licensed indication for the treatment of

newly diagnosed and untreated neovascular (wet) age-related

macular degeneration.

The group does not recommend aflibercept for the same episode of AMD

refractory to treatment with other biological therapies such as ranibizumab.

This recommendation is contingent on a maximum cost per aflibercept

dose as stated in the associated appraisal report.

Clinical evidence

summary

The group accepted that, with clinical data of up to about two years,

aflibercept had demonstrated equivalent efficacy and safety to ranibizumab,

the current standard of care for neovascular AMD. The group observed that

aflibercept may achieve this with fewer doses (injections) and requires a less

intensive monitoring regimen compared with ranibizumab.

The group noted an emerging evidence base demonstrating the efficacy of

aflibercept in AMD cases refractory to aVEGF therapies such as bevacizumab

and ranibizumab. However the group considered this evidence to be of low

quality and insufficient to confirm efficacy and safety in this patient group.

Cost analysis

summary

The group noted the high cost of biological therapies and overall treatment for

neovascular AMD but welcomed the discounts offered by the manufacturers.

The group acknowledged that the drug cost is only one component of the

overall treatment costs. The group concluded that, using discounted drug

prices, aflibercept was unlikely to be more costly and was potentially less

costly than ranibizumab over two years, and subsequent years of on-going

treatment.

Financial impact

PbR: Excluded

The cost of treatment with aflibercept over two years was estimated at about

£15,000 per patient, which is similar to the estimated cost of treatment with

ranibizumab. However both drugs are available to NHS North East

organisations at discounted prices. Using discounted prices, aflibercept is

estimated to yield modest but, potentially, cumulatively significant cost savings

compared with ranibizumab.

Further research

or information

This recommendation with be superseded by a recommendation from the

National Institute for Health and Clinical Excellence (NICE), due to be

published in August 2013.

Not to be used for commercial or marketing purposes

Treatment Appraisal: Decision Summary

ATG-AAA-JAN13. Page 1 of 1

www.netag.nhs.uk

Date 15th January 2013

Appraisal Anti-thymocyte globulin for first-line treatment of adult aplastic anaemia

Details The NHS North East Treatment Advisory Group was requested by a

member organisation to conduct an appraisal of, and issue a

recommendation for, the use of anti-thymocyte globulin (ATG) for the

first line treatment of adult aplastic anaemia for patients who are not

suitable for a bone marrow transplant. The request was prompted by

clinical evidence and guidelines supporting use of horse ATG, an

imported product only licensed in external markets, in preference to

rabbit ATG.

Recommendation The NHS North East Treatment Advisory Group recommends

horse ATG as first-line immunosuppressive therapy in preference

to rabbit ATG for the treatment of adult aplastic anaemia.

Clinical evidence

summary The group acknowledged the substantial difference in efficacy between

horse and rabbit ATG immunotherapy regimens in patients with aplastic

anaemia demonstrated in a single randomised study. The group noted

that this evidence was supported by the majority of data from non-

comparative studies. The group noted recent clinical guidelines which

support horse ATG in preference to rabbit ATG as first-line

immunosuppressive therapy in aplastic anaemia.

Cost analysis

summary The group noted the substantial current estimated cost differential with

horse ATG being about £12,500 more costly than rabbit ATG per

course. However the group also noted that significant off-set costs could

arise from a reduction in the use of subsequent immunosuppressive

therapies and other healthcare resources from the improved efficacy

associated with horse ATG. The group accepted that the cost of horse

ATG was susceptible to potentially large fluctuations due to a number of

external factors.

Financial impact

PbR: Excluded

The only recognised provider within NHS North East estimated about

four to six adult patients per annum, potentially including non-NHS

North East patients. Total incremental costs were therefore estimated to

be a maximum of about £75,000 per annum based on current drug

costs and patient volumes, and assuming one course per patient.

Further research

or information This recommendation applies only to adult patients. Treatment

decisions for paediatric aplastic anaemia patients are the responsibility

of the NHS Commissioning Board.

Not to be used for commercial or marketing purposes

Metolazone withdrawal We have recently learned from Sanofi-Aventis that they are shortly ceasing to manufacture and distribute metolazone. Metolazone is sometimes used for patients with heart failure and intractable fluid retention as an adjunct to loop diuretics as part of "sequential nephron blockade".

Most studies of combination therapy (loop+thiazide) have used metolazone, but Channer showed that metolazone and bendrofluazide were equally effective in inducing diuresis in patients with resistant oedema when added to intravenous frusemide.*

Our advice is to switch patients receiving metolazone to bendroflumethiazide when a patient's supplies run out, at a dose of 2.5 mg, increasing to 5mg, if indicated.

Generic manufacturers may step into the breach, and metolazone is likely to become available again in the UK in the future.

Statement from British Society for Heart Failure, 2012

Administration of intravenous iron in Community Hospital Setting Background Community Hospitals and Step up/Step down units have been approached to administer Intravenous Iron preparations from both General Practitioners and Secondary Care consultants. The current RAG list (updated January 13) covers only one injectable iron preparation locally: GENERIC NAME

BRAND NAME

INDICATION

COMMENT

RECOMMENDED CLASSIFICATION

Ferric carboxymaltose

Ferinject

Iron deficiency when oral iron preparations are ineffective or cannot be used

GREEN GREEN

Lothian formulary gives the following as 1st and 2nd choices for parenteral iron but these are not currently contained within the January 2013 RAG list Iron sucrose Inj Iron dextran Inj

The brand name for Iron sucrose is Venofer and for iron dextran, Cosmofer. In 2008 the request for Ferinject was rejected at APC and the decision appears in the October 2008 edition of Prescription pad. ‘Ferric carboxymaltose (Ferinject®) – rejected as insufficient economic case presented. Manufacturers have indicated that they intend to resubmit.’ There do not appear to be further references to an updated position and therefore the RAG position should actually stand as black not green. Requests to administer parenteral iron preparations have been received by at least 2 known primary care locations, The Eden Assessment Unit and Cockermouth Community Hospital. In response to these requests the products listed in the Lothian formularly and also Ferinject were considered for administration risks based on the NPSA risk tool. With the older iron products anaphylaxis risk and extravasation risk are more of a concern to manage in the community setting. With regards administration within the Community Hospital setting the product Ferinject was considered to be a possible option to be administered for patients referred for administration of parenteral iron. The main benefits are no test dose is required; dosing is less complex so nurses will be more confident in checking that the dose they are administering is correct for the patient, and infusion time is quicker. Whilst there are many other issues to consider regarding prescribing responsibility, dosing and monitoring, purely from the point of view of administration Ferinject would seem the simplest product. At present patients treated in North Cumbria University Hospitals Trust may be prescribed Venofer, Cosmofer and some have been prescribed Ferinject. If

administration of parenteral iron is to be undertaken in the Community Hospitals an agreed product should be chosen for use in the community setting to ensure safety of patients can be maintained. Familiarity with one product will enable experience to built up and reduce any errors associated with use of more complex products. Cost Comparisons. It is difficult to compare costs as there is not therapeutic equivalence between the products. Cost comparisons are shown on page 7 of the attached Scottish Medicines Consortium resource. It should be noted that there is recognition that drug costs are more than likely to be higher using this product over other intravenous iron preparations. Request for its use to be considered in the community hospital setting are based on managing safety risks with administration of intravenous iron in the community hospital setting. Next steps If use of Ferinject is approved, a referral pathway will need to be developed covering referral, referring Clinician responsibilities, responsibility of patients GP, patient responsibility, Community Hospital Team responsibility. It is expected that prescribing responsibility should be in line with RAG traffic light recommendations when clarified for this product. References Scottish medicines Consortium. Resubmission Ferric carboxymaltose 50mg iron/mL solution for injection/infusion (Ferinject®) SMC No. (463/08) Vifor Pharma UK Ltd UCL Hospitals Injectable Medicines Administration Guide: Third Edition. Online guide www.uclhguide.com Nicola McNicol Community Services Pharmacist Cumbria Partnership NHS Foundation Trust. January 29th 2013

Guidelines for the Pharmacological Management of Non-Cancer Pain in Adults Draft version

. Guidelines for the Pharmacological Management of

Chronic Non-Cancer Pain in Adults

Purpose To provide guidance on the pharmacological management of non-cancer pain in adults in Primary Care within Cumbria to ensure that the prescribing of analgesia for patients is evidence based, consistent and cost-effective. Introduction

• Pain is defined as an unpleasant sensory and emotional experience associated with • actual or potential tissue damage, or described in terms of such damage.

(International Association for the Study of Pain). • Pain is one of the most common reasons that patients present to primary care,

accounting for about 5 million GP appointments each year. • According to the British Pain Society, one in seven people are thought to suffer from

chronic pain and 20% of those report suffering for more than 20 years. • Chronic pain is pain that continues beyond the point at which healing would be

expected to be complete, or which occurs in disease processes in which healing does not take place.

• It is known that there are widespread changes within the nervous system that give rise to persistent pain.

• Untreated pain can affect quality of life for sufferers and their carers, leading to helplessness, isolation, loss of work, depression and family breakdown.

• Medication plays only a minor part in managing pain; non-pharmacological measures for pain relief should be considered at all stages of treatment e.g. physiotherapy, TENS, psychological treatments, patient support groups, complementary therapy (acupuncture, reflexology etc.)

• Medication is considered a useful intervention if it reduces the pain score by 50%. • All patients should be screened for common mental health problems that may result

from experiencing difficult to control pain.

Background

• The Royal College of General Practitioners (RCGP) and The Pain Society recommend that primary care physicians and hospital specialists should work together to manage patients in the most appropriate environment.

• Specialist Pain services manage the needs of people with complex pain disorders requiring diagnosis and treatment by a multi-disciplinary team.

• These guidelines are designed to facilitate the treatment pathway between primary and secondary care

Scope

• All patients aged 18 years or over, with non-cancer pain. • For use by all prescribers. The guidelines are not intended to cover all treatments that

may be used by specialist pain services.


Formulating an Analgesic Strategy Chronic pain is complex. Pain perception is altered by social, psychological and cultural context .It is common at all ages but is more common in older people. Drug treatment is only a small component of the management of chronic pain. Patients should be given information and instruction about pain and pain management, and be encouraged to take an active role in their pain management. When an analgesic strategy is being formulated, reference should be made to a patient’s previous experience of pain, analgesics used, any adverse effects and preferences. Renal and hepatic function and age must also be considered. The concept of a multimodal approach to pain management should be employed. Using analgesics with different modes of action improves analgesia and decreases the risk of adverse effects. Choice of analgesia The choice of analgesia should be guided by the principles of the three-step World Health Organisation (WHO) analgesic ladder. This was originally produced for the treatment of cancer pain, but can equally well be applied to pain from other sources, both acute and chronic. The principles of the WHO analgesic ladder can be summarised as follows:

• Analgesics should be prescribed in a logical stepwise manner, with drug choice and dosage tailored to the individual and based on the severity and type of pain and supporting evidence.

• The ladder is a statement of principles, which can be used with a varying degree of interpretation, rather than a rigid framework.

• The ladder advocates the use of three steps for the control of pain. This ascends from non-opioids through weak opioids to strong opioids, according to the severity of pain.

• The underlying principle is that, following good pain assessment and a thorough knowledge of a small number of analgesics, a simple approach should produce pain relief in the majority of patients.

6

WHO's three step ladder to use of analgesic drugs 3

1

2

www.who.int/cancer/palliative/painladder

. The WHO analgesic ladder is widely regarded as being the best approach to the medical management of pain, whether it is acute, chronic, non-malignant or chronic malignant pain


Analgesic Ladder Summary

Assess each change to analgesic regimen after 4 – 6 weeks

Step 1 : Mild Pain (Pain Score 0 – 3) Paracetamol 1g qds +/- NSAID – Ibuprofen 400mg tds or Naproxen 250-500mg bd (with gastro-protection as appropriate)

OA knee or hand

Step 2: Moderate Pain (Pain Score 4-6) STEP 1 plus: weak opioid 1st line: Codeine 30-60mg 4 hourly (max 240mg daily) 2nd line:Tramadol caps 50-100mg 4 hourly (max 400mg daily) Titrate to maximum tolerated dose before switching between agents. Do not prescribe more than one agent from the same class together. +/- Tricyclic antidepressant: amitriptyline (see neuropathic pain guideline) Caution: See Appendix 1 before initiating step 3 opioids Step 3: Severe Pain (Pain Score 7-10) STEP 2 plus: Replace codeine or tramadol with strong opioid: Morphine sulphate SR (as Zomorph capsules) 20mg every 12 hours. Consider lower starting dose in the frail elderly and those with renal impairment. Doses above 60mg twice daily would not be recommended outside of specialist management. + morphine sulphate oral solution (as Oramorph) 10mg/5ml when required for breakthrough pain. If morphine not tolerated consider:

• Tapentadol SR every 12 hours. Start at 50mg twice daily and uptitrate the dose as necessary every 3 days

• Fentanyl transdermal patch (as Matrifen®) every 72 hours for patients who have difficulty swallowing or have problems with opioid-induced constipation despite adequate laxative treatment.

• Oxycodone SR may be prescribed on specialist advice

ALWAYS PRESCRIBE A LAXATIVE WHEN INITIATING STRONG OPIOID

Osteoarthritis of the knee or hand – consider topical NSAID instead of, or in addition to, regular paracetamol (NICE CG 59). Piroxicam gel 0.5% or Ketoprofen gel 2.5%


Why Prescribe Paracetamol? Patients’ opinion of Paracetamol is often poor, perhaps because of its wide availability ‘over the counter’ in supermarkets and other outlets. However:

• Paracetamol is recommended at step 1 of the WHO analgesic ladder and should be prescribed first line as the starting point of any analgesic regime.

• Paracetamol is a very effective drug when taken regularly. • Paracetamol has a very low incidence of side-effects making it a very safe drug at

therapeutic doses; however a dose reduction may be needed if a patient has severe hepatic impairment.

• Paracetamol offers the advantages of low cost, high bioavailability, quick onset of action and the choice of several formulations.

Prescribing Paracetamol with weak opioids The Oxford league table of analgesics in acute pain quotes a number needed to treat (NNT) of 2.2 for the combination of Paracetamol 1g with Codeine 60mg for at least 50% pain relief over 4-6 hours compared to placebo in randomised, double-blind, single-dose studies in patients with moderate to severe pain, compared with a NNT of 16.7 for codeine 60mg alone, highlighting the effectiveness of co-prescribing paracetamol. The efficacy is reduced if either the Paracetamol or the Codeine dose is reduced thus demonstrating the limitations of fixed dose combinations with low dose weak opioids such as Co-Codamol 8/500 or Co-Dydramol 10/500. Patients should be given the individual components where possible to allow titration of dose. However if patients are on a large number of tablets and stable, then a combination may be useful. Effervescent or soluble formulations offer no advantage in patients who are able to swallow tablets, contain high concentrations of sodium, and are expensive. These formulations should be avoided unless there are specific indications (e.g. difficulty swallowing, breakthrough pain). Prescribing of adjuvant drugs (see also neuropathic pain guidelines for prescribing of tricyclic antidepressants, anti-convulsants etc)

Good Practice in NSAID prescribing Step 1: Don’t use them unless you have to

• The only way to avoid NSAID side-effects is not to use them • Paracetamol works for many (see above) • Employ non-drug interventions routinely • Consider short-term course (1-2 weeks) of topical NSAID in OA.

Step 2: If you have to use them, use them wisely General principles:

• Carefully assess balance of risks v benefits especially in relation to CV, GI and renal issues. Caution in patients with asthma.

• Use a safer drug (ibuprofen then naproxen)in the lowest effective dose for shortest period

• NSAID users should be a high priority for medication review. Step 3: Consider gastroprotection in those at high risk

• GI risk factors: age≥65 years, previous peptic ulcer/GI haemorrhage/perforation or stricture, corticosteroid/anticoagulant/antiplatelet therapy, OA/RA, vascular/cardiac/cerebral/liver disease.


Opioids for Chronic Pain Opioids are increasingly being used to treat chronic pain. Opioids have a well-established role in the management of acute pain and pain associated with cancer, but their role in non-cancer pain is less well defined. The safety and efficacy of opioids in the long term is uncertain as is their propensity to cause problems of tolerance, dependence, addiction and intolerable side effects. The benefits of opioid treatment for the patient must therefore be balanced against the risks of long term use (see Appendix 1). The use of opioids for any type of pain should be within the context of the World Health Organisation (WHO) three step analgesic ladder (see above). Non-opioid and adjuvant analgesics should be considered at each step of the ladder. Weaker opioids may be considered at step 2 and stronger opioids should only be considered at step 3 of the ladder. Oral morphine remains the first choice step 3 opioid for most people because of efficacy, familiarity, availability and cost. Choice of Opioid Therapy Codeine is partially metabolised to morphine, which provides its analgesic action. Due to genetic variation, around 10% of European Caucasian population (and a much lower percentage of black and Asian people) will not metabolise codeine in this way and therefore will not respond to codeine. Therefore if patients do not respond to codeine an alternative weak opioid should be tried before considering moving to a strong opioid. Tramadol produces analgesia by two mechanisms: an opioid effect and an enhancement of serotonergic and adrenergic pathways. It is generally considered to have fewer opioid adverse effects; however trial based evidence suggests that tramadol has a similar side-effect profile to codeine and dihydrocodeine. Dizziness and constipation are common, occurring in more than 10% of patients. In addition tramadol has been associated with convulsions and psychiatric reactions (hallucinations and confusion) and has the potential to produce serotonin syndrome when co-prescribed with tricyclic antidepressants and selective serotonin reuptake inhibitors. It can be used in patients with GFR 10-30 ml/min where the dosage interval should be increased to 12 hours. Do not use SR preparations in renal impairment. Tramadol must not be used when the GFR is <10ml/min. Morphine is the strong opioid of choice and there is no evidence of superior clinical analgesic effect for other opioids over morphine. Most patients will develop tolerance to the side effects of morphine, except constipation. Patients with significant renal or hepatic impairment may need a reduced dose of morphine. Modified release preparations should be prescribed by brand name due to variations in release profiles. Zomorph capsules is the current formulary choice. Oxycodone has an efficacy and side effect profile similar to morphine and there are no advantages in using oxycodone first-line in the treatment of moderate to severe pain. It has higher oral bioavailability than morphine, but similar potency, so a 50% dose will give the same analgesic effect. Oxycodone is less likely to accumulate in renal impairment than morphine; however morphine is not contraindicated in renal impairment but dosage reduction and longer dosing intervals are recommended. Oxycodone is still contraindicated in severe renal impairment GFR <30ml/min (CKD 4 and 5). Oxycodone is several times more expensive than the equivalent dose of morphine in both standard and slow release preparations.


Fentanyl patches should be reserved for patients with stable pain who are already taking a strong opioid and are unable to tolerate oral medication, or for whom the oral route is not possible. A 25 microgram patch is equivalent to a 24 hour oral morphine dose of 60 – 90mg (see appendix for opioid dose conversions). Fentanyl patches should never be prescribed for opioid-naïve patients. They lack the flexibility required in patients with fluctuating pain or for titrating in uncontrolled pain. An effective plasma concentration is usually reached 12-24 hours after the first patch is applied, but steady-state concentrations may not be reached until the second patch is put on. Fentanyl patches may differ between brands depending on the type of patch used (matrix or reservoir) and it may not be suitable to switch patients from one type to the other. The recommended formulary brand of fentanyl patch for all new patients is Matrifen®. Heat increases the release of fentanyl from patches so patients should be monitored for increased side-effects if fever is present as increased absorption is possible. Exposing the application site to external heat e.g. hot water bottles, electric blankets, hot bath etc. should also be avoided as this may also increase absorption. Fentanyl products designed for breakthrough pain such as lozenges, nasal preparations and buccal tablets have been given a black traffic light within the Lothian Joint Formulary (http://www.cumbria.nhs.uk/ProfessionalZone/MedicinesManagement/TrafficLight/RAGlist.xls) and are therefore not recommended for prescribing, with the exception of the sublingual formulation of fentanyl (Abstral®) which is limited to prescribing for patients with persistent cancer pain who are opioid tolerant. Tapentadol is a new opioid analgesic with additional noradrenaline reuptake inhibitor properties. Only the modified-release form of tapentadol (Palexia SR®) has been approved and its use restricted for the treatment of severe chronic pain which can be adequately managed only with opioid analgesics when morphine sulphate modified-release has failed to provide adequate control or is not tolerated. In a meta-analysis, tapentadol prolonged-release demonstrated non-inferior efficacy, but superior gastro-intestinal (GI) tolerability compared to oxycodone modified-release (MR) tablets. There is a lack of long-term efficacy data and of comparative data with opioid analgesics other than oxycodone. Tapentadol SR should be used with caution in patients with moderately impaired hepatic function. Its use has not been studied in patients with severe hepatic or renal impairment and therefore use in these patients is not recommended.

The equi-analgesic dose ratio of tapentadol to morphine is 2.5:1 and to oxycodone is 5:1(e.g. 50mg tapentadol is equivalent to 20mg morphine or 10mg oxycodone).

Other considerations Predictable side effects of opioids should be anticipated and managed (see also appendix 1) Constipation is a long term side effect for around 90% of patients who will need regular laxatives for prophylaxis. To help prevent opioid-induced constipation, and potential noncompliance with treatment, patients prescribed long-term opioid medications should be considered for a scheduled regimen of laxatives, especially if constipation is a pre-existing problem. Using lower doses of opioids will not prevent constipation because the dose that produces constipation is approximately 4-fold less than the analgesic dose Effective treatment and management of constipation usually requires a combination of a stimulant and stool softener e.g. senna + docusate. Macrogol is the preferred choice in the immobile, elderly and those prone to constipation. Nausea and vomiting occurs in approximately 60% of patients for the first 3-5 days.. Consider metoclopramide 10mg tds for five days or haloperidol 1.5mg at night. Nausea often settles and anti-emetics can be discontinued, but may recur when dose increases. See appendix 1 for information regarding the long-term side-effects of opioids.


Appendix 1: Points to discuss with patients before initiating

chronic (long-term) opioid therapy

• Opioids are increasingly being used to treat chronic non-cancer pain. However, the safety and efficacy of opioids in the long term is uncertain as is the propensity for these drugs to cause problems of tolerance, dependence and addiction. Clinical trials of opioid efficacy suggest that the drugs can provide useful analgesia in the short and medium term. Data demonstrating sustained analgesic effectiveness in the longer term are lacking.

• The decision to start long term opioid therapy should be considered carefully by the

prescriber, the patient and his/her carers and other members of the healthcare team as therapy for persistent pain may need to be continued for months or years. It is important that patients are adequately informed of the risks and benefits of opioid therapy by supplementing discussions with written information.

• Assessment of the patient in pain should include a history of the patient’s mental health, in particular screening questions for depression and substance misuse disorders.

• Improvements in quality of life are unlikely to be achieved unless opioids are prescribed as part of a broader approach to improve patient function.

• Prescribing opioids for elderly patients should take account of relevant age-related changes in pharmacokinetics and pharmacodynamics. Starting doses should be cautious with frequent reassessment and dose adjustment as appropriate.

• If patients do not achieve useful relief of pain symptoms at doses between 120-180mg morphine equivalent in 24 hours, referral to a specialist in pain medicine is strongly recommended as there are no high quality data published that inform prescribers of the safety and efficacy of higher doses.

Goals of therapy/ patient expectations

Opioids are prescribed to reduce pain intensity. Complete relief of pain is rarely achieved with opioids. The goal of therapy is to reduce symptoms sufficiently to support improvement in physical, social and emotional functioning. This should be agreed before starting opioid treatment and assessed at each review.

British Pain Society has developed a patient information booklet Opioids for persistent pain:Information for patients http://www.britishpainsociety.org/book_opioid_patient.pdf


Adverse effects

1. Short-term effects • 80% of patients taking opioids will experience at least one adverse effect. The

commonest adverse effects are: constipation; nausea; somnolence; itching; dizziness; vomiting.

• Adverse effects should be managed actively with antiemetics, laxatives and antihistamines as appropriate.

Management of constipation

• Inform patients that constipation affects most patients receiving strong opioid treatment

• Prescribe laxative treatment (to be taken regularly at an effective dose) for all patients initiating strong opioids

• Inform patients that treatment for constipation takes time to work and adherence is important

• Optimise laxative treatment for managing constipation before considering switching strong opioids.

Management of nausea

• Advise patients that nausea may occur when initiating strong opioids or at dose increase, but that it is likely to be transient

• If nausea persists, prescribe and optimise anti-emetic treatment before switching opioids

Management of drowsiness

• Advise patients that mild drowsiness or impaired concentration may occur when starting strong opioid treatment or at dose increase, but that it is often transient.

• Warn patients that impaired concentration may affect their ability to drive and undertake other manual tasks.

2. Long-term effects

Patients must be aware of uncertainty regarding the long term effects of opioids, particularly in relation to endocrine and immune function and the risk of inducing a hyperalgesic syndrome.

Endocrine effects

• Long term administration of opioids is associated with endocrine impairment in both men and women.

• These effects are probably dose related and can lead to amenorrhoea, reduced libido, infertility and depression in women and erectile dysfunction and diminished libido in men.

• Patients (particularly women of childbearing age) should be told about these effects before starting opioids. Endocrine function should be monitored regularly if symptomatically indicated and patients should be referred to an endocrinologist for advice regarding the benefits of hormonal replacement therapy.


Immunological effects

• Both animal and human studies have demonstrated that opioids have an immunomodulating effect. These effects are mediated via opioid receptors both on immune effector cells and in the central nervous system. Opioids may differ in their propensity to cause immunosuppression.

Opioid induced hyperalgesia

• Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain can become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or can be different from it.

• OIH is not the same as tolerance. Tolerance is characterized by decreasing efficacy of the drug, which can be overcome by increasing the dose, whereas OIH cannot be overcome by increasing the dosage since it is a form of pain sensitization induced by the drug which occurs within the CNS. In fact, increasing the dosage worsens the pain and conversely, pain is improved by reducing or eliminating the opioid.

Driving while on opioid therapy

UK laws allow patients who are taking prescribed opioids for pain relief to drive.

Patients taking opioids are banned from driving if their use constitutes drug misuse or dependency.

Patients being treated with opioids should be advised to avoid driving when:

• the condition for which they are being treated has physical consequences that might impair their driving ability;

• they feel unfit to drive; • they have just started opioid treatment; • their dose of opioids has been recently adjusted upwards or downwards (as withdrawal

may have an impact on capability) • they have consumed alcohol or other drugs that can produce an additive sedative effect • It is the patient’s responsibility to advise the DVLA that they are taking opioid medication. Prescribers should document that this advice has been given.

Review

Patients being considered for long term treatment with opioids should have a carefully supervised trial of opioid therapy with evaluation of analgesic efficacy and adverse effects.

During long term treatment, reviews should be conducted at least monthly in the first six months after stable dosing has been achieved. Frequency of review thereafter can be clinically determined by the complexity of the case, but should be at least biannually.

If opioids have been started in secondary care, there should be agreement between the hospital and the patient’s GP regarding where and by whom the patient will be assessed and who should provide the repeat prescriptions. In both primary and secondary care, arrangements must be made for the provision of prescriptions when the patient’s principal prescriber is unavailable.


Appendix 2 Analgesics to be avoided in primary care

Drug name/ group Comments

Buprenorphine patch (Butrans® / Transtec®)

Cost effectiveness not proven. Lack of good quality comparative data versus other opioid preparations.

Buprenorphine tablets (Temgesic®)

Not recommended due to abuse potential.

Capsaicin patch 179mg (Qutenza®)

This is classified as RED so specialist prescribing only for post-herpetic neuralgia.

Co-dydramol Has similar analgesic effect to paracetamol alone but with additional opioid side-effects

Co-proxamol Marketing authorisation cancelled in 2007.No longer licensed due to safety concerns, particularly toxicity in overdose.

COX-2 inhibitors Not recommended in patients with cardiovascular disease. There is no evidence that COX-2 inhibitors are significantly safer than non-selective NSAIDS in the general patient population.

Dihydrocodeine Local experience with dihydrocodeine is that it may be abused in the community and should be avoided if possible.

Dipipanone +cyclizine Prescribing is discouraged due to the risk of abuse

Fentanyl buccal tablets / lozenges (Effentora® / Actiq®)

Sublingual formulation (Abstral®) preferred. Restricted to persistent cancer pain. Buccal not recommended due to possible confusion.

Fentanyl nasal spray (Instanyl®, PecFent®)

Classified as BLACK in the traffic light system and thus not recommended for prescribing.

Paracetamol +tramadol (Tramacet®)

Prescribe drugs individually as compound preparations do not allow for effective dose titration; the advantages of using a compound formulation have not been substantiated.

Pethidine Do not prescribe pethidine for chronic pain as it has a short duration of action, greater misuse potential and is no more effective than other opioids.

Oxycodone + naloxone (Targinact®)

Not recommended for routine prescribing as it has not demonstrated sufficient clinical or cost effectiveness.

Antimicrobial Management of Infective Exacerbations of non-CF Bronchiectasis in Adult In-patients

Adapted for local use from British Thoracic Society Bronchiectasis Guideline Thorax 2010 (see link (1) for full guideline) Note that patients admitted with exacerbations of bronchiectasis should usually be managed on a respiratory ward under the care of a specialist physician. Sputum microbiology H. influenzae is the most frequently isolated pathogen, being found in up to 35% of patients. P aeruginosa is isolated from 5 to 31% of adult patients.

All patients with bronchiectasis should have an assessment of lower respiratory tract microbiology. (D)

When does an exacerbation require antibiotic therapy? Antibiotics should be given for exacerbations that present with an acute deterioration with worsening symptoms (cough, increased sputum volume or change in viscosity, increased sputum purulence with or without increasing wheeze, breathlessness, haemoptysis) and/or systemic upset. Which antibiotic regimen is recommended? The antibiotic chosen should be based on local microbial patterns, sensitivities and cost. Bear in mind that repeated use of antibiotics leads to a significant chance of resistance with poor clinical response. Quinolones (e.g., ciprofloxacin) are associated with Clostridium difficile colitis, particularly in elderly patients. See Table 1 for local recommendations.

Before starting antibiotics, a sputum sample should be sent off for culture. (D) Empirical antibiotics should be started whilst awaiting sputum microbiology. (D) Previous sputum bacteriology results can be useful in deciding which antibiotic to use.

(C) Antibiotics can be modified subsequently once the pathogen is isolated only if there is no

clinical improvement and the treatment should then be guided by antibiotic sensitivity results. (D)

Failure to respond to an antibiotic course should prompt a repeat sputum culture. (D) When are combination antibiotics regimens required? Combination antibiotics should be used for infections due to strains of P aeruginosa that are resistant to one or more antipseudomonal antibiotics (including ciprofloxacin) or if the clinician suspects the patient will require many subsequent antibiotic courses to reduce the development of drug resistance. (D)

http://www.brit-thoracic.org.uk/Portals/0/Clinical Information/Bronchiectasis/non-CF-Bronchiectasis-guideline.pdf

Is there a role for long term oral antibiotics? Preliminary studies have shown potentially beneficial immunomodulatory effects of certain antibiotics (macrolides) on host inflammatory response. Further trials are required to investigate this disease-modifying activity.

Patients having ≥3 exacerbations per year requiring antibiotic therapy or patients with fewer exacerbations that are causing significant morbidity should be considered for long-term antibiotics. (C)

The antibiotic regimen should be determined by sputum microbiology when clinically stable. (D)

As there is a high risk of resistance with continuous use of ciprofloxacin in patients colonised with P aeruginosa, this drug should be avoided in this patient group.

Is there clinical relevance of in vitro antibiotic resistance patterns? The prevalence of antimicrobial resistance in the common pathogens shows regional variation even within the UK, emphasising the significance of local antimicrobial susceptibility patterns.

Treatment should be guided on antibiotic sensitivity results but is often empirical based on previous sputum bacteriology. (D)

Some patients may respond to antibiotic treatment despite resistance to that drug in vitro. Antibiotics should only be changed if there is no clinical response. (D)

Table 1. Recommended antimicrobials for empirical in-patient management of acute infective exacerbations of bronchiectasis in adults

Clinical scenario Recommended regimen No previous relevant bacteriology (suitable for oral therapy)

AMOXICILLIN oral, 500mg every 8 hours or CLARITHROMYCIN oral, 500mg every 12 hours (if penicillin allergic)

No previous relevant bacteriology (severe infection)

CO-AMOXICLAV IV, 1.2 grams every 8 hours ± GENTAMICIN IV, daily (see link for dose) or CEFUROXIME IV, 1.5 grams every 8 hours ± GENTAMICIN (if mild penicillin allergy*)

Colonisation with H influenzae AMOXICILLIN oral, 1 gram every 8 hours (if sensitive) Colonisation with P aeruginosa CEFTAZADIME IV, 3 grams every 12 hours (if sensitive) Colonisation with MRSA (suitable for oral therapy)

DOXYCYLINE oral, 200mg once daily ± RIFAMPICIN oral, 300 to 600mg every 12 hours

Colonisation with MRSA (severe infection)

Discuss with microbiology consultant

Deterioration despite first line antibiotics

Discuss with respiratory physician and/or microbiology consultant

*Discuss with microbiologist if severe penicillin allergy/anaphylaxis. • Modify antibiotic regimen according to culture results and clinical response. • Typical course length: 10-14 days. • IV to oral switch is not usually appropriate for patients who have required admission,

although oral antibiotics may be used in the outpatient setting. • Note that it may be possible to complete the course of IV antibiotics in the community –

suggest discussion with the respiratory specialist nurse or respiratory physician. Version 1 October 2011 Antimicrobial management team. Agreed by consultant respiratory physicians.

http://nww.staffweb.cumbria.nhs.uk/acute/services-and-departments/pharmacy/Abx Gent.pdf

From: Taylor Caroline (A82017) BrunswickHouse CA1 1ED

Sent: 10 January 2013 13:59

To: Brown Mairead (A82017) BrunswickHouse CA1 1ED; Coakley Gareth(A82017) BrunswickHouse CA1 1ED; Corrigan Christopher (A82017) BrunswickHouse CA1 1ED; Edgar Andrew (A82017) BrunswickHouse CA1

1ED; Hartley Anne (A82017) BrunswickHouse CA1 1ED; Marshall Ian (A82017) BrunswickHouse CA1 1ED; Nolan Jane (A82017) BrunswickHouse CA1 1ED; Patterson Colin (A82017) BrunswickHouse CA1 1ED;

Sanders Tim (A82017) BrunswickHouse CA1 1ED; Siddle Stephanie (A82017) BrunswickHouse CA1 1ED;

Sixsmith Mark (A82017) BrunswickHouse CA1 1ED; Smith Karen (A82017) BrunswickHouse CA1 1ED; Westgate Robert (A82017) BrunswickHouse CA1 1ED

Subject: hospital discharges FYI Just had a conversation with the pharmacist at Dalston about a new system they appear to be using at CIC for ‘blister’ pack patients. The patients are being discharge with NO take home meds. Instead they fax an FP10 to chemist then they make up the tray. Then post the original to them. We are still going to be the last to receive the discharge summaries it seems ! Caroline ----------------------------------------------------------------------------------------------------------------------------- -------------------

From: Patterson Colin (A82017) BrunswickHouse CA1 1ED


To: Weaving Peter (A82012) Brampton Medical Practice Subject: FW: hospital discharges FYI

Peter Can you substantiate the content of this e-mail? Is it acceptable to medicine management group in Cumbria? Does medicine management have any influence over the trust or is it a law onto itself I thought it was mandatory that the trust send people home with a set number of days treatment in their hands. In fact I remember they had specific resources transferred to them to do this when this was decided several years ago. What were the consultation processes that lead to this outcome? It just makes the trust look like it is not a team player and if anyone falls through the cracks the GP will have to generate a script from flimsy information Colin

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From: Weaving Peter (A82012) Brampton Medical Practice Sent: 14 January 2013 11:39

To: Patterson Colin (A82017) Brunswick House CA1 1ED

Subject: RE: hospital discharges FYI

You’re absolutely right, Colin, an agreement was reached regarding the provision of, and funding for, 28-days of discharge medication. It was additionally agreed that when a patient was on e.g furosemide 40mg daily and had just started the pack in their POD (Patients Own Drugs - personally held in locker stock of medication, moves around the hospital with the patient) they would reasonably be discharged with less than 28 days but not less than 14.

Regarding compliance aids eg blister packs I understand the situation currently is that CIC pharmacy needs 48 hours for this kind of discharge medication and if unable to provide this in a timely manner the request goes to the patient’s preferred community pharmacy. I am meeting the Bill Glendinning (Chief Pharmacist NCUH) in the very near future so it would be helpful if you could let me know what would be your, and your colleagues, preferred mechanism is here. Peter

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From: Glendinning Bill (RNL) North Cumbria University Hospitals

Sent: 14 January 2013 15:24 To: Angell Lesley (5NE) NHS Cumbria; Loudon Andrea (5NE) NHS Cumbria

Subject: FW: hospital discharges FYI Can I suggest the subject of compliance aids, but not the contents of this e-mail, is put on the LPN agenda in February? Haven’t got a firm date yet, but if it’s the 4th then unfortunately I won’t be able to make it unless it’s in the afternoon. There has been an awful lot of water gone under this particular bridge since 2003, including the introduction of PbR which reputedly pays for this now. The big issue for us at the moment(and we aren’t the only Trust in the country suffering from this) is the quick turnaround of patients, the scenario of a change in one medication in a blister pack and then discharge within 24-48hrs of admission and the insistence of some providers that they will only accept patients back into their care if their meds are in a compliance aid. Its an almost impossible task within the resources we have. At the moment we have instances of 4hrs or less notice being given of a discharge involving these devices and they are disproportionately sucking up our resources to provide them, and of course we get the blame for delaying discharge when we can’t. A measured response from Peter. Do you happen to know what the various policies of the independents and multiples are regarding provision of these devices are? I thought 48hrs notice was standard. Bill ----------------------------------------------------------------------------------------------------------------------------- -------------------

From: Angell Lesley (5NE) NHS Cumbria Sent: 15 January 2013 15:34

To: Glendinning Bill (RNL) North Cumbria University Hospitals; Loudon Andrea (5NE) NHS Cumbria

Subject: RE: hospital discharges FYI

I’ve just had a chat with Mark Stakim from Dalston Pharmacy, the discharge that triggered this was a request from one of the elderly care wards, and was requested because the patient was being discharged that day. Mark agreed to pack up a tray on receipt of a faxed script and have it ready for collection/deliver it (not sure what happened in this case) when the patient went home. He has had two requests like this since last Monday. Interestingly, one was for a patient who lived with their daughter and the other had carers 4 times a day, so did either actually need a tray? My concern with this is that Mark’s operation is capable of turning requests round this quick, but I very much doubt any of the others are, and the potential for patients missing meds is huge. He did say to the ward that he couldn’t possibly do a tray if he got the call in the afternoon, again, I can envisage pts being taken home in the afternoon/evening and not getting the tray delivered until the following late morning/afternoon. As far as the practices are concerned, the issue of being last to get the discharge info hasn’t changed, Mark was hoping that when he came to request the next prescription, the practice would have received the discharge info in the post. Incidentally, he was having to chase the ward for the prescriptions, neither had been received! I can also see why the ward need to discharge the patient and cant justify delaying 48 hours while waiting for a tray, but who has decided that a tray is necessary, and who decided this was a possible way of circumventing the 48 hour notice? If every rapid tray discharge goes via Mark, he’s going to pretty soon not be able to provide a same day service! Then there is the whole issue of carers (family and paid carers) and trays….

I don’t want to fan the flames of this, Andrea, do you think we reply that we are going to discuss at the LPN and will feedback to the locality after that and if Bill discusses with Peter when they meet? Lesley ------------------------------------------------------------------------------------------------------- -----------------------------------------

From: Glendinning Bill (RNL) North Cumbria University Hospitals


To: Angell Lesley (5NE) NHS Cumbria; Loudon Andrea (5NE) NHS Cumbria Subject: RE: hospital discharges FYI

Will discuss this with Peter tomorrow. LPN good place to discuss, but wonder if this is now something for APC to discuss. CIC have opened up 12 bed rehab unit without additional pharmacy resource. Leaving internal politics aside, they have FP10HPs ie no cost to GP to facilitate discharge with community pharmacist on the basis these patients should not be sudden discharges but planned. If being discharged immediately then will take that back to our medical unit. Mark is not helping himself or anybody else in the long term by agreeing to do this at such short notice. I cannot tell the wards that they have to plan these things if they then find that someone will turn these trays around quickly. They will then come to expect that kind of service from anyone. And what happened to the Equality act assessment for compliance aids, because we certainly aren’t doing them. In point of fact Dr Corrigan in the last round made some valid points that trays are for the convenience of the carers not the patient. Refusing to provide them is also not the answer. Aware some Trusts do refuse, but also aware it causes significant issues in terms of comms between the Trust and a community pharmacist willing to take them on. In terms of discharge documentation will copy you in on some transformational change happening at the moment. Bill

APC = Area Prescribing Committee, CG = Clinical Guidelines (NICE), FAF1 = Formulary Application Form (Lothian), LJF = Lothian Joint Formulary, NETAG = North of England Treatment Advisory Group, SIGN = Scottish Intercollegiate Guidelines Network, SMC = Scottish Medicines Consortium, TA = Technology Appraisal (NICE)

DEVELOPING AND UPDATING LOCAL FORMULARIES

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Cumbria

2.1 Relationships with other decision-‐making bodies

2.1.1 When developing or reviewing the local formulary, map and understand the functions of existing medicines-‐related networks and decision-‐making groups in the local and neighbouring health economies.

External influences in Cumbria that need to be considered are/will be:

• UHMB (straddles Cumbria and North Lancs)

• NCUH (being subsumed by Northumbria Hospitals NHS Foundation Trust)

At present Northumbria has not been involved in Cumbria decision making.

2.1.2 Avoid duplicating work by collaborating with other local decision-‐making groups.

Cumbria uses the LJF as a basis for most decisions on drugs. There are circumstances where LJF decisions are overridden, e.g. where NICE recommendation differs from SMC recommendations.

Cumbria APC is the only drug decision-‐making group in Cumbria (apart from trusts who may decide on ‘in-‐hospital’ treatments)

2.1.3 Proactively identify, consider and implement recommendations in publications from national decision-‐making bodies, such as NICE, taking appropriate actions (see recommendations.

NICE TA’s and CG’s are standing items at LJF meetings. Only multiple TA’s are binding in Scotland, it is considered to be helpful to compare LJF decisions with SMC recommendations.

NICE TAs and CG are standing item on APC meetings.


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Cumbria

2.2 Formulary scope 2.2.1 Determine the scope of the local formulary through consultation with all locally defined stakeholders. Consider the:

• size of patient population to be covered • range of healthcare treatments to be included • range and number of partner organisations

adopting the formulary.

Formulary decisions are adopted by Acute Trusts where they affect primary care, but they can make their own decisions where drug is for in-‐patient use only.

2.2.2 Ensure local arrangements actively consider: • consistency of care pathway arrangements across

the patient population • clinical engagement • resources needed to operate formulary processes.

Cumbria has insufficient resources available to have its own formulary process.

2.3 The local formulary decision-‐making group

2.3.1 Agree and document terms of reference for the local formulary decision-‐making group. This should include:

• clarification of budgetary responsibility None, but LJF will advise on possible impact (costs and savings) of adoption of new drugs

None, but APC will advise on possible impact (costs and savings) of adoption of new drugs

• lines of accountability and reporting arrangements • members' roles and responsibilities • declaration of interest arrangements Standard reminder and agenda item

at every meeting Standard reminder and agenda item at every meeting

• arrangements for quoracy Requires presence of: • One of co-‐chairmen • Hospital consultant • GP

• arrangements for deputies None None • pre-‐meeting preparation and post-‐meeting actions Agenda sent out about 10 days prior

to meeting Agenda sent out about 7 days prior to meeting


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• the method by which final decisions will be made, recorded and disseminated

Minutes Minutes

• actions of the Chair To chair meeting To inform clinical leads in writing of decisions on new drugs. Finance copied into correspondence

None

• frequency of meetings 6 weekly 8 weekly

2.3.2 Include a locally-‐defined mix of members from partner organisations and key stakeholders, such as patients and the public.

Representation from Acute, MH and primary care. No patients or lay members present

Representation from Acute, MH and primary care. Patient representative is member

2.3.3 Use the National Prescribing Centre's Local decision-‐making competency framework to ensure membership has the appropriate range of skills and expertise needed to undertake all necessary activities.

2.3.4 Hold meetings sufficiently frequently to ensure decision-‐making is robust and decisions are made in a reasonable and practical time frame.

Interval considered to be balance of other work and attendance at meeting

Interval considered to be balance of other work and attendance at meeting

2.3.5 Ensure resources are available to undertake all functions needed as determined by the scope and geographical coverage of the local formulary.

2.3.6 If operating a local formulary covering a small population, consider sharing resources and establishing joint processes with neighbouring local formulary decision-‐making groups to avoid duplicating work.

Although not a small population, Cumbria does not have sufficient resources to provide adequate quality of formulary process

2.3.7 Ensure corporate governance arrangements are firmly established with clear lines of accountability for each partner organisation.


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2.3.8 Report to relevant corporate governance bodies for each partner organisation appropriately, and as a minimum annually, and by exception when needed.

2.4 Stakeholder engagement

2.4.1 Ensure local strategies include stakeholder engagement with:

• clinical groups and networks, especially if a formulary decision needs specific knowledge and expertise or has direct implications for a clinical practice area

FAF 1 forms are completed by lead clinician in area. They are expected to consider use of new drug within local policy etc.

Recommendations from local clinical networks are considered during the decision making process

• patients or patient representative groups SMC seek input from patient representative groups for all new drug appraisals

• local people and communities None None • relevant manufacturers of medicines, for example,

when the company can offer additional evidence and insight that can assist with decision-‐making

SMC consults drug companies and seeks their views and additional data where necessary

• other relevant decision-‐making groups Decisions from NETAG are considered. These are usually on the use of drugs outside licensed indications

2.4.2 Ensure stakeholder engagement is proportionate to the type of decision being made and the medicine being considered.

2.5 Processes for selecting medicines to be considered

Recommendations for proactive identification of medicines for consideration 2.5.1 Include horizon scanning as a standing agenda item in local formulary decision-‐making group meetings.

All new drugs proactively considered by SMC and then LJF.

Input from SMC/LJF. Yearly Prescribing Outlook from UKMI considered.

2.5.2 Include NICE technology appraisals as a standing agenda item in local formulary decision-‐making group meetings.

Yes Yes


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2.5.3 When a NICE technology appraisal does not recommend a medicine, focus discussions and actions on withdrawing and decommissioning the medicine from the formulary, in line with NICE recommendations.

Not routinely done. Not routinely done.

2.5.4 Prioritise medicines not subject to a NICE technology appraisal for consideration using explicit criteria. Ensure these prioritisation criteria are well known, clear and transparent. Consider:

All new drugs considered. All new drugs considered.

• impact on patient care • timelines for new medicines reaching the market • severity of disease and patient numbers affected • clinical effectiveness • patient safety • gaps in treatment or other available treatments • cost effectiveness • resource impact • inappropriate variation in local current practice.

Recommendations for reactive identification of medicines for consideration 2.5.5 Ensure the process for adopting, removing or updating new medicines or indications is clear, robust and transparent. Applications should be submitted by a clinician, although manufacturers may support evidence gathering.

LJF is updated on a rolling basis or when there is:

• Significant change made due to new drug going onto formulary

• New safety guidance • Significant cost savings due to

drugs coming off patent.

2.5.6 Provide information to the applicant to explain how the process will operate and ensure application forms are readily available. Consider inviting the applicant to a meeting to allow for constructive discussion.

LJF has all forms on website. Applicants are not invited to meetings.


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2.5.7 Ensure the following information is included in application forms for new medicines or indications to be considered:

• details of the clinician making the application, including a declaration of interests

Standard question on submission form

• local patient population Standard question on submission form Cumbria figures (500k) correlated from Lothian population (800k)

• details of the medicine, including strength, formulation, therapeutic drug class, indication, monitoring requirements and cost

Standard question on submission form

• evidence submission with relevant supporting literature, including efficacy, safety and cost effectiveness

Standard question on submission form or from SMC appraisal

• comparison with existing treatments Expert opinion from clinical lead sought

• likely place in therapy Expert opinion from clinical lead sought

• recommendation for the decommissioning of a current formulary medicine, if applicable resource impact.

Not done

2.6 Adoption of NICE technology appraisal recommendations

2.6.1 Include medicines with a positive NICE technology appraisal into the local formulary automatically, if clinically appropriate and relevant to the services provided by the organisation. This process should take place within 3 months. Include the medicine within the relevant care pathway(s), in line with NICE recommendations.

Not relevant, apart from multiple technology appraisal TA’s.

2012 adoption of NICE guidance average is 45 days, none exceeded 90 days


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2.6.2 If a NICE technology appraisal states 'option for treatment', adopt the medicine into the local formulary, and if necessary, identify its place in the relevant care pathway(s) provided by local organisation(s), in line with NICE recommendations.

2.7 Setting decision criteria

2.7.1 Clearly define and consistently apply standard criteria for decision-‐making. Develop and/or apply a multi-‐criteria decision tool, which should include:

All applied as part of the overall process

• patient safety • clinical effectiveness • cost effectiveness or resource impact • strength of evidence • place in therapy relative to available treatments • national guidance and priorities • local health priorities • equity of access • stakeholder views.

2.8 Evidence and information gathering

2.8.1 When there is a NICE technology appraisal for a medicine, do not duplicate NICE's evidence assessment or make a challenge to a technology appraisal recommendation.

This is not done.

2.8.2 When there is no NICE technology appraisal for a medicine, use NICE clinical guidelines and other sources of high-‐quality information produced by national and regional horizon scanning organisations, if available. Ensure these are relevant to the medicine and indication being considered. Avoid duplicating effort locally.

SMC and LJF are not bound by CG’s, but consider them as a method of assessing current practice. LJF adopts other national guidance (and also SIGN guidance)

APC recommends the use of national guidelines where these are appropriate, e.g., hypertension and asthma guidelines.


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2.8.3 If local critical appraisal and evidence synthesis is needed, ensure that evidence-‐gathering strategies comprehensively reflect the requirements set out in the local formulary's decision-‐making criteria.

Data collection strategy uses on-‐line literature databases, outputs from UKMI and NICE Medicines and Prescribing, national guidelines as well as work from other health bodies in UK.

2.8.4 If local critical appraisal and evidence synthesis is needed, ensure that individuals with specialist skills and competencies are available. This includes skills in:

• literature searching • critical appraisal interpreting and contextualising

evidence.

Pharmacist with suitable skills is member of APC and provides background material.

2.9 Incorporating new information from regulatory authorities

2.9.1 Incorporate drug safety updates routinely into the local formulary. This could be achieved by having patient safety updates as a standing agenda item

Drug Safety Update and manufacturer drug safety circulars are standing item on agenda.

Drug Safety Update is standing item on agenda.

2.10 Assessment of financial and commissioning impact

2.10.1 Routinely engage with commissioning and financial managers at an appropriate level of seniority and align local formulary decisions within the framework of clinical commissioning

2.10.2 Address barriers that may delay the speed of adoption of medicines into the formulary, such as multiple applications to different decision-‐making groups, delayed or absent business planning, budget identification or service design.

2.11 Deliberating and reaching decisions

2.11.1 Use explicit principles that are formally documented to guide deliberation, such as mission statements, terms of reference, decision criteria and legal and ethical frameworks.


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2.11.2 Support individuals in deliberation and decision-‐making by providing appropriate training and constructive feedback.

2.11.3 Determine explicitly how local formulary decision-‐making groups reach final decisions.

By consensus. Voting is not undertaken.

By consensus. Voting is not undertaken.

2.12 Documentation 2.12.1 Document the deliberations and actions from meetings, the outcomes of decisions, the rationale for each decision and all formulary policies thoroughly.

Documented via minutes Documented in minutes and key points distributed in Prescription Pad.

2.12.2 Use a standard format for notes and minutes which ensures that the key points are summarised for all decisions. Ensure secretariat functions are sufficiently competent so that technical information is accurately recorded.

2.13 Decision outputs 2.13.1 Develop decision outputs with stakeholders (including clinical groups and networks) and other local decision-‐making groups in a timely manner, to prevent delays in access to treatment.

2.13.2 Develop decision outputs related to a NICE technology appraisal within a time frame that does not delay the adoption of the medicine into the formulary beyond the statutory requirements

2.14 Communication and dissemination

2.14.1 Publish all relevant local formulary information online, in a clear, simple and transparent way, so that patients, the public and stakeholders can easily understand it. This includes formulary policies, minutes of meetings, decision outcomes and associated decision outputs.

Key points distributed in Prescription Pad and in RAG list on website.

2.14.2 Publish information that sets out which NICE technology appraisals are included in the local formulary, in line with the NHS Chief Executive's letter Innovation, Health and Wealth publication of NHS formularies.


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2.14.3 Develop a local communication framework, in consultation with stakeholders, reviewed annually, to:

• disseminate targeted, concise information to other decision-‐making groups and key stakeholders, including patients and the public who need to know about the decision

• routinely communicate with neighbouring local formulary decision-‐making groups to share practice, particularly when there are cross-‐boundary patient flows

• anticipate media response to decisions.

2.15 Reconsideration and appeals of decisions

2.15.1 Establish a robust and transparent process for reconsideration or appeals of decisions made by the local formulary decision-‐making group. Ensure relevant information is clear and easily accessible.

SMC and LJF allow appeals on decisions based if based on new data only

2.15.2 Clearly define the criteria for a clinician to request a reconsideration of a decision made by the local formulary decision-‐making group. This should include circumstances in which:

• significant new information such as a drug safety alert has become available, which requires a reconsideration of the evidence

• the decision was based on inaccurate or incomplete information.

2.15.3 Clearly define the acceptable grounds for a clinician to appeal a decision made by the local formulary decision-‐making group. This should include circumstances in which the local formulary decision-‐making group is judged not to have followed the published process.


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2.15.4 Ensure the validity of a formal appeal is assessed by an independent appeals panel. The appeals panel should inform the clinician, in writing, if the appeal does not satisfy the defined grounds. The appeals panel should direct appeals that do satisfy the defined grounds to the most appropriate decision-‐making group for further consideration.

SMC has an independent appeals panel, LJF does not.

AJF does not have an appeals panel.

2.15.5 Ensure the appeals panel has a clear statement of purpose. Members should together have the skills and expertise necessary to enable them to make the decisions being asked of them.

2.15.6 Secure adequate training and resources to operate the appeals process. Consider collaborating with neighbouring groups to provide independent cross-‐organisational appeals panels.

2.16 Review and updating

2.16.1 Establish a robust and transparent process for reviewing and updating the local formulary. This includes:

• ensuring new positive NICE technology appraisal recommendations are incorporated into the formulary automatically

Single TA’s are not applicable in Scotland (but there is a high degree of agreement anyway).

This is done automatically as new appraisals are published.

• ensuring that when a NICE technology appraisal does not recommend a medicine, the medicine is withdrawn from the formulary, in line with NICE recommendations

Single TA’s are not applicable in Scotland (but there is a high degree of agreement anyway).

This is done automatically as new appraisals are published.

• responding to important new evidence on all medicines included in the formulary in a timely manner, including withdrawing or amending the position of a medicine in the care pathway(s)


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• responding promptly to important new information on drug safety, such as serious adverse effects

This is done in response to Drug Safety Update and manufacturers notifications.

This is done in response to Drug Safety Update.

• reviewing and updating associated decision outputs • ensuring requests to review and reconsider the

evidence are considered in a timely manner

• responding promptly to the identification of technical errors

• responding promptly to the outcome of appeals • establishing a rolling schedule of structured

formulary review.

2.16.2 Collaborate effectively with relevant stakeholders, including clinicians and other local decision-‐making groups.

Northern England NHS Treatment Advisory Group DRAFT PROPOSAL

NE(NHS)TAG Page 1 of 3

Proposal for a

Northern England NHS Treatment Advisory Group

NE(NHS)TAG

Status: Northern England NHS TAG will be a locally mandated network of the

Northern England Clinical Senate.

Outputs: Treatment recommendations will have advisory status only. Therefore

recommendations will be non-binding however there will be agreement to implement

recommendations consistently across member organisations. See appendix for list of

member organisations. Each treatment recommendation will be accompanied by a

robust and open appraisal with a corresponding appraisal report published.

Scope: NHS primary and specialist (secondary, tertiary and mental health) care

sectors.

Remit: Treatments, including drug, non-drug, unlicensed and off-license treatments,

which are being used for, or may be used for, NHS patients who are the

responsibility of a member commissioning organisation. Priority will be given to

treatments which are considered high-cost, or for which patient volumes or pathways

may not concur with usual referral patterns, or first-in-class new therapeutic agents,

or novel treatments. Based on the experiences of the NHS North East Treatment

Advisory Group about two-thirds of treatment appraisals are expected to relate to

drugs or similar. Treatment appraisals will be conducted where there is a clear

rationale and advantages from a consistent regional approach.

The group will not consider treatments which are within the remit of the NHS

Commissioning Board, or for which relevant NICE technology appraisal guidance

exists or is due to be available within six months of the next scheduled meeting of

the group.

Meetings: Six meetings scheduled between April 2013 and March 2014, to fall

approximately once every two months.

Representation at meetings: Fourteen members plus a group secretary.



Membership: NHS mental health, hospital and commissioning organisations within

the geographical footprint of the Northern England Clinical Senate (appendix).

One reserved place each for representation from;

1. Mental health trusts

2. Specialist regional tertiary-level care providers

i. City Hospitals Sunderland NHS Foundation Trust

ii. South Tees Hospitals NHS Foundation Trust

iii. The Newcastle upon Tyne Hospitals NHS Foundation Trust

3. Northumbria Healthcare NHS Foundation Trust, incorporating North Cumbria

University Hospitals

4. All other hospital trusts typified by the district general hospital model

One place reserved for patient or lay representation.

One place reserved for public health specialist representation.

Six places reserved for CCG members of the Northern England CCG Forum from

which the chair and deputy-chair of the group will be nominated. The six CCG

representatives must include:

1. Three practicing general medical practitioners

2. A senior and experienced medicines management adviser

3. A director of finance or director of commissioning or similar

4. A chief officer or chief operating officer or similar

For each representative position a lead and one or more deputy representatives will

be nominated to ensure that attendance at meetings is comprehensive. CCG

representatives should not be concentrated from any particular CCG or locality. The

lead representative for each position will be expected to attend each meeting or to

arrange for one of their nominated deputies to attend in the event that they are

unable to attend.



Appendix. Member organisations of the proposed Northern England NHS Treatment Advisory Group

Mental Health Trusts

Cumbria Partnership NHS Foundation Trust

Northumberland, Tyne and Wear NHS Trust

Tees, Esk and Wear Valleys NHS Foundation Trust

Hospital Trusts

City Hospitals Sunderland NHS Foundation Trust

County Durham and Darlington NHS Foundation Trust

Gateshead Health NHS Foundation Trust

North Tees and Hartlepool NHS Foundation Trust

Northumbria Healthcare NHS Foundation Trust, incorporating North Cumbria University Hospitals

South Tees Hospitals NHS Foundation Trust

South Tyneside NHS Foundation Trust

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Clinical Commissioning Groups

Cumbria (Copeland, Allerdale, Eden and Carlisle localities only)

Darlington

Durham Dales, Easington and Sedgefield

Gateshead

Hambleton, Richmondshire and Whitby (Hambleton and Richmondshire localities only)

Hartlepool and Stockton-on-Tees

Newcastle North and East

Newcastle West

North Durham

North Tyneside

Northumberland

South Tees

South Tyneside

Sunderland

Latest advice for medicines users The monthly newsletter from the Medicines and Healthcare products Regulatory Agency and its independent advisor the Commission on Human Medicines

Volume 6, Issue 5, December 2012

Contents Drug safety advice Carbamazepine, oxcarbazepine and eslicarbazepine: serious skin reactions

associated with the HLA-A* 3101 allele A1

Stop press Evicel fibrin sealant spray application: life-threatening and fatal air embolism – updated advice on minimising risk

S1

Codeine-containing pain relief in children: safety review initiated following post-surgical fatalities in ultra-rapid metabolisers

S2

End of year quiz Test your drug-safety knowledge O1

The Medicines and Healthcare products Regulatory Agency is the government agency which is responsible for ensuring that medicines and medical devices work, and are acceptably safe. The Commission on Human Medicines gives independent advice to ministers about the safety, quality, and efficacy of medicines. The Commission is supported in its work by Expert Advisory Groups that cover various therapeutic areas of medicine.

For full details on our accreditation visit NHS Evidence http://www.evidence.nhs.uk/ Accreditation

In this issue: the risk of serious skin reactions induced by carbamazepine may be increased in patients of European descent or Japanese origin with the HLA-A*3101 allele. However, there are currently insufficient data to support screening for this allele before starting carbamazepine treatment. Patients of European descent or Japanese origin who are known to be positive for this allele should only receive carbamazepine, oxcarbazepine or eslicarbazepine after careful consideration of the benefits and risks (see article A1) Also this month: see article S1 for news on life-threatening and fatal reports of air embolism occurring with the use of sprayable fibrin sealants. Such events appear related to a higher-than-recommended spray pressure, or spraying too close to the tissue surface. Following a Europe-wide review, updated advice on the correct use of the fibrin sealant Evicel has been issued. Reviews of other fibrin sealants are being finalised and updated advice on these will be provided very soon. A European review of the safety of codeine-containing pain-relief medicines used in children has been initiated. The review was triggered by very rare, non-UK reports of fatalities, and life-threatening respiratory depression, in children who had been given codeine for post-operative pain following tonsillectomy or adenoidectomy. These children were found to be ultra-rapid or extensive codeine metabolisers. See article S2 for more information. Finally, try our end-of-year quiz to test yourself on some of the key safety advice provided in 2012. You may also be able to use the completed quiz to claim Continuing Professional Development points (see article O1). We wish all of our readers a very happy New Year. Priya Venkatesan, Editor [email protected]

http://www.evidence.nhs.uk/Accreditation


mailto:[email protected]

Drug safety advice

A1 Carbamazepine, oxcarbazepine and eslicarbazepine: serious skin reactions associated with the HLA-A* 3101 allele

The risk of serious skin-related adverse drug reactions, including Stevens-Johnson syndrome, occurring with carbamazepine may be increased in the presence of the HLA-A*3101 allele in patients of European descent or Japanese origin. However, there are currently insufficient data to support screening for this allele before starting carbamazepine treatment. Patients of European descent or Japanese origin who are known to be positive for this allele should only receive carbamazepine, oxcarbazepine or eslicarbazepine after careful consideration of the benefits and risks.

See: April 2008 Drug Safety Update [link to: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON084888] Carbamazepine Summary of Product Characteristics [link to: http://www.medicines.org.uk/EMC/medicine/1328/SPC/Tegretol+Tablets+100mg%2c+200mg%2c+400mg/] References: 1] Phillips EJ et al. Drug hypersensitivity: pharmacogenomics and clinical syndromes. J Allergy Clin Immunol. 2011 Mar; 127(3 Suppl): S60 – 66. 2] Mushirada T, Nakamura Y. Personalizing carbamazepine therapy. Genome Med. 2011 May; 3(5): 2. 3] Mehta TY et al. Association of HLA-B1502 allele and carbamazepine–induced Stevens-

Carbamazepine (Tegretol) is an antiepileptic drug that is indicated for the treatment of generalised tonic clonic seizures. Carbamazepine is also licensed to treat the paroxysmal pain of trigeminal neuralgia and for the prophylaxis of manic-depressive psychosis in patients unresponsive to lithium therapy. Oxcarbazepine (Trileptal) is indicated for the treatment of partial seizures with or without secondary generalisation and is closely structurally related to carbamazepine. Eslicarbazepine (Zebinix) is the active metabolite of oxcarbazepine and indicated as adjunctive therapy in adults with partial onset seizures with or without secondary generalisation. It is well-recognised that severe, potentially life-threatening, skin-related adverse drug reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), can occur rarely in association with carbamazepine. The frequency of such skin reactions has been estimated to be about one to six cases per 10 000 new users of carbamazepine in the USA and Europe. Human leukocyte antigens (HLA) are involved in some drug-specific abnormal immune responses including SJS and TEN), and the HLA allele HLA-B*1502 is known to be highly associated with carbamazepine-induced SJS and TEN in certain Asian populations[1,2]. We informed you in 2008 of the association between carbamazepine-induced SJS and HLA-B*1502 in patients of Han Chinese, Hong Kong Chinese and Thai origin, with advice to screen these individuals for HLA-B*1502 before starting carbamazepine treatment. Since 2008, new study findings have become available suggesting an association with serious skin-related adverse drug reactions, including Stevens-Johnson syndrome, and HLA-B*1502 in other Asian populations [3,4]. In addition, the clinical utility of HLA-B*1502 screening before starting carbamazepine treatment has recently been shown in Han Chinese individuals [5]. More recently, a new genetic marker, HLA-A*3101, has been identified in Japanese individuals and individuals of European descent for serious carbamazepine-induced cutaneous adverse drug reactions such as SJS, TEN, and drug rash with eosinophilia (DRESS), and less severe reactions such as acute generalised exanthematous pustulosis (AGEP) and maculopapular rash[6,7]. The frequency of HLA-A*3101 varies widely between ethnic populations, with a prevalence of 2 – 5% in European populations and approximately 10% in the Japanese population. The presence of the HLA-A*3101 allele may increase the risk for carbamazepine-induced cutaneous reactions (mostly less severe reactions) from 5% to 26% in patients of European descent. Its absence may reduce the risk from 5% to 3.8% in patients of European descent. However, the sensitivity of the HLA-A 3101 test for SJS in European and Japanese patients is relatively low (5/12 cases [42%] in

http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON084888


http://www.medicines.org.uk/EMC/medicine/1328/SPC/Tegretol+Tablets+100mg%2c+200mg%2c+400mg/



Johnson Syndrome among Indians. Indian J Dermatol Venereol Leprol 2009;75: 579 – 582 4] Chang CC et al. Association of the HLA-B1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens- Johnson Syndrome in the multi- ethnic Malaysian population. Int J Dermatol 2011; 50(2):221 – 224 5] Chen P et al. Carbamazepine- induced toxic effects and HLA-B1502 screening in Taiwan. N Eng J Med 2011; 364: 1126 – 1133. 6] Ozeki T et al. Genome-wide association study identifies HLA-A3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet 2011; 20(5): 1034 – 1041 7] McCormack M et al. HLA-A3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Eng J Med 2011; 364: 1134 – 1143

patients of European descent and 5/6 cases [83%] in Japanese patients) when compared to the HLA-B*1502 test for SJS (where sensitivity approaches 100%)[7]. It is also noteworthy that the number of patients included in the HLA-A*3101 studies was small and there are no prospective studies on the clinical utility of HLA-A* 3101 testing in any population. Currently there are insufficient data supporting a recommendation for HLA-A*3101 screening before starting carbamazepine or chemically-related medicines. If patients of European descent or Japanese origin are known to be positive for HLA-A*3101, the use of carbamazepine or chemically related compounds may be considered, but only after careful consideration of the expected benefits of treatment and the increased risk of serious skin conditions. Data supporting an association of HLA-A *3101 with oxcarbazepine and eslicarbazepine-induced skin reactions are very limited but due to their close structural relationship with carbamazepine and reports of hypersensitivity with cross reactivity, the advice has been extended to cover not only carbamazepine but these two structurally related products.

Further information: BNF section 4.8 Antiepileptic drugs [link to: http://www.medicinescomplete.com/mc/bnf/current/PHP2898-control-of-the-epilepsies.htm]

Advice for healthcare professionals:

Carbamazepine is associated with a risk of potentially life-threatening skin-related adverse drug reactions, including Stevens-Johnson syndrome. If signs and symptoms suggestive of severe skin reactions appear, treatment should be withdrawn at once and alternative treatment should be considered

The presence of the HLA-A*3101 allele may increase the risk for

carbamazepine-induced skin reactions in patients of European descent or Japanese origin

If patients of European descent or Japanese origin are known to be

positive for HLA A*3101 they should only receive carbamazepine, oxcarbazepine, or eslicarbazepine after careful consideration of the benefits and risks

Article citation: Drug Safety Update December 2012 vol 6, issue 5: A1.

http://www.medicinescomplete.com/mc/bnf/current/PHP2898-control-of-the-epilepsies.htm



Stop press

S1 Evicel fibrin sealant spray application: life-threatening and fatal air embolism – updated advice on minimising risk

Further information: Press release from the European Medicines Agency [link to: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/11/news_detail_001659.jsp&mid=WC0b01ac058004d5c1]

Fibrin sealants (also known as tissue adhesives or glues) are used in a wide range of surgical procedures to rapidly arrest bleeding and assist in subsequent wound healing. They are applied either by dripping or spraying onto the tissue surface. There have been reports of life-threatening and fatal cases of air embolism occurring in association with the use of spray devices employing pressure regulators to administer fibrin sealants. Such events appear to be related to the use of the spray device at higher-than-recommended pressures, and/or in closer-than-recommended proximity to the tissue surface. We first informed you of this risk in October 2010. Worldwide, a total of six reports have been received of life-threatening or fatal air embolism with the sprayable fibrin sealants Evicel (5 reports) and Tisseel (1 report), and a further four reports in association with Quixil, a sprayable fibrin sealant which is no longer available in the UK. Following a recent European review of the benefits and risks of these products, a number of recommendations have been made for Evicel to minimise the risk of air embolism when this medicine is applied as a spray during surgery. Advice for healthcare professionals:

For spray application of Evicel using a pressure regulator device, only CO2 gas should be used (not pressurised air)

When spraying Evicel in open-wound surgery, the maximum pressure should

be 1.7 bar (25 psi). The product should be sprayed at least 10 cm or more from the tissue surface

When spraying Evicel in laparoscopic surgery, the maximum pressure should

be 1.4 bar (20 psi). The product should be sprayed at least 4 cm or more from the tissue surface, and only used if the spray distance can be accurately judged

Do not use Evicel in other endoscopic procedures

Prior to applying Evicel, the surface area of the wound should be dried using

standard techniques (eg, intermittent application of compresses, swabs, and use of suction devices)

Closely monitor blood pressure, heart rate, oxygen saturation and end-tidal

CO2 when spraying Evicel, because of the possibility of air embolism

Please report suspected adverse reactions with fibrin sealants through the Yellow Card Scheme at www.mhra.gov.uk/yellowcard

Reviews of other fibrin sealants (Tisseel Ready for use solution for sealant, Tisseel Lyo, Artiss solution for sealant, deep frozen) are being finalised, and we will provide updated advice very soon.

Article citation: Drug Safety Update December 2012 vol 6, issue 5: S1.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/11/news_detail_001659.jsp&mid=WC0b01ac058004d5c1




Stop press

S2 Codeine-containing pain relief in children: safety review initiated following post-surgical fatalities in ultra-rapid metabolisers

See: European review of codeine-containing pain relief in children [link to: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Codeine_containing_medicinal_products/human_referral_prac_000008.jsp&mid=WC0b01ac05805c516f] FDA communication [link to: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315601.htm] BNFc section 4.7.2 Opioid analgesics [link to: http://www.medicinescomplete.com/mc/bnfc/current/PHP12346-codeine-phosphate.htm#PHP12349]

Codeine is a widely used opioid analgesic and is sometimes used for post-operative pain relief in children. A European review of the safety of medicines containing codeine licensed for pain relief in children (aged 0-18 years) was started in October 2012. The ongoing review was triggered by recent concerns that there is an increased risk of morphine toxicity when certain susceptible children are given codeine for post-operative pain after surgery. These concerns follow the reporting of three fatalities, and one life-threatening case of respiratory depression in children given codeine after tonsillectomy or adenoidectomy in the treatment of obstructive sleep apnoea [1,2]. The US Food and Drug Administration (FDA) have also communicated on this issue. The risk of post-surgery respiratory depression in certain susceptible children following codeine use may be due to their genetically determined rate of codeine metabolism. Codeine is metabolised to morphine via the cytochrome P450 enzyme CYP2D6 and genetic differences in the expression of this enzyme, according to racial or ethnic group, determine the extent to which codeine is metabolised. A faster metabolism results in higher-than-normal blood levels of morphine which can lead to toxic effects such as breathing difficulties. Up to approximately 6.5% of Caucasians may be ultra-rapid metabolisers of codeine (the frequency varies between countries). The three fatal cases following post-surgical codeine occurred in children who had evidence of being ultra-rapid metabolisers of codeine; the life-threatening case of respiratory depression occurred in a child who was defined as an extensive metaboliser [1,2]. The BNF for Children contains a note for caution with regard to variable metabolism for codeine and the marked increase in side-effects that can occur with rapid metabolism. The European review will evaluate the impact of the new information on the balance of benefits and risks of codeine-containing medicines when used for pain relief in children. The outcome of the review will be communicated when available. Advice for healthcare professionals Clinicians should remain aware that patients may respond differently to codeine.

Those caring for patients taking codeine should be advised to seek professional help if symptoms of toxicity occur

Symptoms of codeine toxicity include reduced levels of consciousness, lack of

appetite, somnolence, constipation, respiratory depression, ‘pin-point’ pupils, nausea and vomiting

Article citation: Drug Safety Update December 2012 vol 6, issue 5: S2.

http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Codeine_containing_medicinal_products/human_referral_prac_000008.jsp&mid=WC0b01ac05805c516f





http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315601.htm



http://www.medicinescomplete.com/mc/bnfc/current/PHP12346-codeine-phosphate.htm#PHP12349



End-of-year quiz

Do you read Drug Safety Update every month? Then test your knowledge of drug safety in our annual quiz. If you participate in Continuing Professional Development/Continuing Medical Education, you may be able to use the completed quiz as evidence of learning through reading of Drug Safety Update. To claim personal CPD points in this way, we suggest you keep a copy of the quiz, together with your answers and the bulletin articles. The answers are given at the bottom of the quiz. Some articles in Drug Safety Update are more relevant for some healthcare professionals than for others, so feel free to attempt only the questions related to your specialty. Please do not send your answers to us, this quiz is just for fun! 1 Paracetamol overdose is sometimes treated with acetylcysteine (Parvolex and generics). What approach to treatment should always be taken when there is doubt over the timing of paracetamol ingestion? 2 Inadvertent switching between oral tacrolimus products has been associated with reports of toxicity and graft rejection. How should oral tacrolimus prescriptions be written in order to minimise this risk? 3 What adverse effect associated with the antibacterial chlorhexidine should healthcare professionals be aware of, and prepared for? 4 Which electrolyte disturbance can occur with long-term proton pump inhibitor (PPI) treatment? Monitoring for this electrolyte disturbance should be considered especially in patients taking which other drugs? 5 Acute pancreatitis has been reported with use of all drugs in which class of drugs for the treatment of type 2 diabetes mellitus? Name two members of this class of drugs? 6 The combination of aliskiren with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is not recommended for any patient groups. Why? In which patient groups is the combination absolutely contraindicated? 7 What is the new maximum recommended dose of simvastatin when used with amlodipine or diltiazem? Why has this limitation been introduced? 8 Which non-selective non-steroidal anti-inflammatory drug (NSAID) has a cardiovascular risk that is higher than other non-selective NSAIDs, and similar to the selective COX-2 inhibitors? 9 What risk with ondansetron has resulted in a new maximum single intravenous dose for the management of chemotherapy-induced nausea and vomiting (CINV) in adults? What is the new maximum dose in this setting?

10 How can you report a suspected adverse drug reaction? Quiz answers 1 Always give acetylcysteine without delay. See http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON185624 2 Prescribe and dispense oral tacrolimus products by brand name only. See http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON155756 3 Hypersensitivity, including generalised allergic reactions and anaphylactic shock. See http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON140701 4 Hypomagnesaemia. Healthcare professionals should consider measuring magnesium levels before starting PPI treatment and repeat measurements periodically during prolonged treatment, especially in those who will take a PPI concomitantly with digoxin or drugs that may cause hypomagnesaemia (eg, diuretics). See http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON149774 5 The dipeptidylpeptidase-4 (DPP-4) inhibitor class of antidiabetic agents (‘gliptins’). Drugs in this class include Onglyza▼ (saxagliptin), Trajenta▼ (linagliptin), Galvus▼ (vildagliptin) and Januvia (sitagliptin). A number of fixed-dose combination tablets containing a DDP-4 inhibitor with metformin are also available, including Eucreas▼ (vildagliptin) and Janumet (sitagliptin). See: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON185628] 6 Following concerns raised in the ‘ALTITUDE’ study, a review of all data confirmed a risk of adverse outcomes (hypotension, syncope, stroke, hyperkalaemia, and changes in renal function including acute renal failure) when aliskiren is combined with ACE inhibitors or ARBs. This combination is not recommended for any patient and is contraindicated in patients with type I or type II diabetes; and non-diabetic patients with impaired renal function - eGFR <60 mL/min per 1.73 m2 See: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON146526] 7 The maximum recommended dose for simvastatin in conjunction with amlodipine or diltiazem is now 20 mg/day. These changes were driven primarily by concerns about an increased risk of myopathy and/or rhabdomyolysis at higher plasma concentrations of simvastatin, which may result from such drug combinations. See: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON180637] and: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON199561] 8 Diclofenac is associated with cardiovascular risks that are higher than the other non-selective NSAIDs, and similar to the selective COX-2 inhibitors. See: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON199570 ]










9 There is a greater risk of prolongation of the electrocardiographic-corrected QT interval (QTc), a known side effect of ondansetron, when it is used at the higher doses previously authorised for CINV. The new maximum dose in this setting is 16 mg infused over at least 15 minutes See: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON180635 ] 10 Report suspected adverse drug reactions via the Yellow Card Scheme—the simplest way to report is via www.mhra.gov.uk/yellowcard

Article citation: Drug Safety Update December 2012 vol 6, issue 5: O1.

© Crown Copyright 2012


Latest advice for medicines users The monthly newsletter from the Medicines and Healthcare products Regulatory Agency and its independent advisor the Commission on Human Medicines

Volume 6, Issue 6, January 2013

Contents Drug safety advice Fingolimod (Gilenya▼): bradycardia and heart block – repeat enhanced

cardiovascular monitoring when restarting fingolimod after treatment interruptionA1

Lenalidomide (Revlimid): risk of serious hepatic adverse drug reactions – routine monitoring of liver function now recommended

A2

Stop press Tredaptive (combined niacin-laropiprant) – no longer for prescribing since preliminary HPS2-THRIVE trial failed to show benefit outweighs risks

S1

Roflumilast (Daxas▼): risk of suicidal behaviour – avoid use in patients with previous or existing psychiatric symptoms and discontinue treatment if new or worsening psychiatric symptoms occur

S2

Other information from the MHRA

Learning about Yellow Card reporting and pharmacovigilance O1

New MHRA Twitter channel on medicines’ safety O2

The Medicines and Healthcare products Regulatory Agency is the government agency which is responsible for ensuring that medicines and medical devices work, and are acceptably safe. The Commission on Human Medicines gives independent advice to ministers about the safety, quality, and efficacy of medicines. The Commission is supported in its work by Expert Advisory Groups that cover various therapeutic areas of medicine.

For full details on our accreditation visit NHS Evidence http://www.evidence.nhs.uk/ Accreditation

In this issue: we provide advice on new cardiovascular monitoring requirements for fingolimod (Gilenya▼) if treatment is interrupted and restarted. We also provide a reminder of existing advice to minimise the risk of cardiovascular adverse events (see article A1). Also this month: routine monitoring of liver function is now recommended for all patients receiving lenalidomide (Revlimid) for multiple myeloma, particularly for patients with a history of, or concurrent, viral liver infection or those receiving concomitant medication associated with a risk of liver injury. This advice follows a number of reports of serious hepatic reactions with lenalidomide use (see article A2). The European Medicines Agency has recommended that the licence for Tredaptive (fixed-dose combination product containing extended-release nicotinic acid [1000 mg]) and laropiprant [20 mg]) should be suspended, after a review showed that the benefits of this product no longer outweigh the risks. Tredaptive has been recalled from 18th January 2013. Patients currently taking Tredaptive should be reviewed at a non-urgent appointment in order to consider the need for alternative treatment options (see article S1 for more information). And finally: we update you on roflumilast (Daxas▼) and the risk of suicidal behaviour which has been reported in patients with and without a history of depression, usually within the first few weeks of treatment. Treatment should be avoided in patients with a history of depression associated with suicidal ideation or behaviour, and discontinued if new or worsening psychiatric symptoms occur (article S2). Priya Venkatesan, Editor [email protected]



mailto:[email protected]

Drug safety advice

A1 Fingolimod (Gilenya▼): bradycardia and heart block – repeat enhanced cardiovascular monitoring when restarting fingolimod after treatment interruption

Starting fingolimod treatment, or re-starting fingolimod after treatment interruption, results in transient decreases in heart rate. In some patients it can also cause transient bradycardias and heart block. This risk is minimised through enhanced monitoring. Guidance on when enhanced cardiac monitoring is required following treatment interruption has now been updated on the basis of new clinical pharmacology analyses and dose titration data. The new monitoring advice depends both on the time since treatment started, and how long treatment has been interrupted for (see main article below for details).

See: Fingolimod Summary of Product Characteristics [http://www.medicines.org.uk/EMC/medicine/24443/SPC/Gilenya+0.5mg+hard+capsules#CLINICAL_PRECAUTIONS]

Fingolimod (Gilenya) is authorised to treat relapsing-remitting multiple sclerosis in patients whose disease has failed to respond to beta-interferon or is severe and getting worse rapidly. Fingolimod is a sphingosine -1 phosphate receptor ligand. Initiation of fingolimod treatment causes a transient reduction in heart rate and a decrease in atrioventricular conduction after the first dose, including the occurrence of heart block. We first highlighted the need for strengthened monitoring after the first dose of fingolimod in February 2012 and in May 2012 as set out below and provided in more detail in the Summary of Product Characteristics (SPC):

• All patients should be monitored before, during, and immediately after the first 6 hours of treatment

• If the patient’s heart rate decreases to its lowest point at the end of the 6-hour treatment period, monitoring should be extended until heart rate increases

• Monitoring should also be extended at least overnight if significant atrioventricular block, bradycardia, or QTc prolongation occurs.

Because the effects of fingolimod on heart rate and atrioventricular conduction may recur on reintroduction of fingolimod treatment following interruption, we also advised that if fingolimod was stopped for more than 2 weeks for any reason, patients should be monitored in the same way as those starting treatment. Now, further (unpublished) analyses of clinical pharmacology and dose titration data suggest the risk of these cardiovascular effects depends on the duration of the interruption and also the time since initiation of fingolimod treatment. New advice based on these findings is provided below, along with new advice to repeat the monitoring on day 2 in patients who required pharmacological treatment for symptoms of bradyarrhythmia on Day 1.

New advice Treatment interruption: The same first-dose monitoring as for treatment initiation* should be repeated if treatment is interrupted as follows: • 1 day or more during the first 2 weeks of treatment. • more than 7 days during weeks 3 and 4 of treatment. • more than 2 weeks after one month of treatment.

http://www.medicines.org.uk/EMC/medicine/24443/SPC/Gilenya+0.5mg+hard+capsules#CLINICAL_PRECAUTIONS




See: Fingolimod SPC [http://www.medicines.org.uk/EMC/medicine/24443/SPC/Gilenya+0.5mg+hard+capsules#CLINICAL_PRECAUTIONS] Further information: BNF section 8.2.4 Other immunomodulating drugs [link to http://www.medicinescomplete.com/mc/bnf/current/4789.htm]

If the treatment interruption is of shorter duration than the above, the next dose of fingolimod should be given as planned without repeating the first-dose cardiovascular monitoring. Patients should be provided the following simplified advice: ‘If you have been taking Gilenya for less than 1 month and you forget to take 1 dose for a whole day, call your doctor before you take the next dose. Your doctor may decide to keep you under observation at the time you take the next dose. If you have been taking Gilenya for at least 1 month and have forgotten to take your treatment for more than 2 weeks, call your doctor before you take the next dose. Your doctor may decide to keep you under observation at the time you take the next dose. However, if you have forgotten to take your treatment for up to 2 weeks, you can take the next dose as planned. Never take a double dose to make up for a forgotten dose’. Following pharmacological intervention to treat bradyarrhythmia-related symptoms after first dose: As per current recommendations, patients requiring pharmacological intervention during the first dose monitoring should be monitored overnight in a medical facility. In these patients, it is now recommended to repeat the first-dose monitoring* after the second dose of Gilenya. *Key advice, such as first-dose monitoring requirements and high-risk patients in whom fingolimod is not recommended, is listed in the SPC. Reporting of suspected adverse drug reactions

• Please report all suspected adverse reactions to fingolimod to the Yellow Card Scheme at http://www.mhra.gov.uk/yellowcard

A letter containing the updated advice was sent to health professionals in January 2013.

Article citation: Drug Safety Update January 2013 vol 6, issue 6: A1.

A2 Lenalidomide (Revlimid): risk of serious hepatic adverse drug reactions – routine monitoring of liver function now recommended

Elevations of liver enzymes occur in 1-10 patients out of every 100 treated with lenalidomide for multiple myeloma in clinical trials; the majority of these are non-serious. Serious (potentially fatal) liver injuries such as acute hepatic failure, toxic hepatitis, hepatocellular hepatitis, and cholestatic hepatitis have been reported overall in <1% of treated patients. Hepatic function should be routinely monitored (with the same frequency as haematological monitoring*), particularly in patients with a history of, or concurrent, viral liver infection, or when lenalidomide is given at the same time as other medications known to be associated with liver injury.

Lenalidomide (Revlimid) is authorised in combination with dexamethasone for treatment of multiple myeloma in patients who have received at least one previous treatment. Lenalidomide is an immunomodulatory agent similar to thalidomide, and has





http://www.medicinescomplete.com/mc/bnf/current/4789.htm

http://www.medicinescomplete.com/mc/bnf/current/4789.htm

http://www.mhra.gov.uk/yellowcard

See: Updated lenalidomide Summary of Product Characteristics [link to: http://www.medicines.org.uk/EMC/medicine/19841/SPC/Revlimid/] and Patient Information Leaflet [link to: http://www.medicines.org.uk/EMC/medicine/19842/PIL/Revlimid/ ].

antineoplastic, antiangiogenic, and proerythropoietic properties. Lenalidomide was introduced in the UK in June 2007. Risk of hepatic adverse drug reactions Suspected adverse hepatic reactions have been reported overall in <1% of patients treated. Of these reactions, abnormal liver investigation results, and clinical signs and symptoms of hepatic disorders are the most common (58.7%). The spectrum of hepatic suspected adverse reactions reported also includes hepatic failure, fibrosis, and cirrhosis (17.2%); and cholestasis and jaundice of hepatic origin (13.8%). The remaining reports (10%) describe non-infectious hepatitis, liver-related coagulation and bleeding disorders, and neoplasms. The outcome was fatal in 5% of cases. In many of the cases, including most with a fatal outcome, there were confounding risk factors for liver disease such as history of hepatic and renal disorders including viral hepatitis; progression of myeloma; myeloma involvement of the liver; prior chemotherapy; infection or sepsis; and concomitant medications known to cause liver injury, particularly antibiotics. Out of nine liver biopsies performed in patients with hepatic reactions, six showed histological evidence of drug-induced liver injury. In addition, there have also been a substantial number of cases where liver function has improved on discontinuation of lenalidomide, some cases of positive rechallenge, and some cases of negative rechallenge at a lower dose. Clinical implications of the evidence for drug-induced liver injury with lenalidomide The evidence suggests that lenalidomide may be associated with drug-induced liver injury. The most compelling evidence of a causal association derives from the results of liver biopsies, and cases in which there has been a positive dechallenge or a positive rechallenge. The most common hepatic reactions observed in patients treated with lenalidomide are abnormalities of liver enzymes presenting as hepatocellular injury, and/or with a cholestatic pattern. Elevations of liver enzymes frequently occur relatively soon after the start of treatment with lenalidomide; the median time to onset appears to be 41 days, but reactions have been reported from one day to more than three years after the start of treatment. Early elevations in liver enzymes are usually moderate and may normalise without progression to major liver toxicity. Serious liver injury due to lenalidomide has been reported in relatively small numbers of patients and appears to be idiosyncratic. Predisposing factors that may increase the risk of serious liver injury with lenalidomide include elevated baseline liver enzymes; pre-existing viral liver disease; concomitant treatment with known hepatotoxic medicines; and older age.

Further information: Letter for healthcare professionals sent December 2012 [link to: http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con218766.pdf ] Report suspected adverse reactions via the Yellow Card Scheme: www.mhra.gov.uk/yellowcard European Public Assessment Report for lenalidomide (Revlimid): [link to:

Advice for healthcare professionals:

• Routine monitoring of liver function with the same frequency as haematological monitoring* is recommended for patients receiving lenalidomide. This is particularly important in patients with a history of, or concurrent, viral liver infection, or when lenalidomide is given at the same time as other medications known to be associated with liver injury.

• Prescribers should consider the possibility of lenalidomide-induced liver injury in

patients presenting with otherwise unexplained deterioration of liver function. • Impairment of liver function generally resolves when lenalidomide treatment is

stopped. Once abnormal liver function parameters return to baseline, resumption

http://www.medicines.org.uk/EMC/medicine/19841/SPC/Revlimid/

http://www.medicines.org.uk/EMC/medicine/19841/SPC/Revlimid/

http://www.medicines.org.uk/EMC/medicine/19842/PIL/Revlimid/

http://www.medicines.org.uk/EMC/medicine/19842/PIL/Revlimid/

http://www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con218766.pdf




http://www.mhra.gov.uk/yellowcard

http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000717/human_med_001034.jsp&mid=WC0b01ac058001d124] BNF section 8.2.4 Other immunomodulating drugs [link to http://www.medicinescomplete.com/mc/bnf/current/PHP5713-lenalidomide.htm ]

of treatment with lenalidomide at a lower dose may be considered. • Reminder advice: lenalidomide is excreted predominantly by the kidney. It is

important to adjust the dose of lenalidomide in patients with renal impairment to avoid high plasma levels which may increase the risk of severe hepatotoxicity, as well as haematological side effects.

*The haematological monitoring recommendations for lenalidomide are as follows: a complete blood cell count, including white blood cell count with differential count, platelet count, haemoglobin, and haematocrit should be performed at baseline, every week for the first 8 weeks of lenalidomide treatment and monthly thereafter to monitor for cytopenias.

Article citation: Drug Safety Update January 2013 vol 6, issue 6: A2.

Stop press

S1 Tredaptive (combined niacin-laropiprant) – no longer for prescribing as preliminary HPS2-THRIVE trial failed to show benefit outweighs risks

See: EMA press release, December 2012 [http://www.emea.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/12/news_detail_001686.jsp&mid=WC0b01ac058004d5c1] HPS2-THRIVE study [http://www.ctsu.ox.ac.uk/research/mega-trials/hps2-thrive] EMA press release, January 2013 [http://www.emea.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/01/news_detail_001694.jsp&mid=WC0b01ac058004d5c1]

Tredaptive is a fixed-dose combination product containing extended-release nicotinic acid (1000 mg) and laropiprant (20 mg), which has been indicated for the treatment of dyslipidemia, particularly in patients with combined mixed dyslipidemia and in patients with primary hypercholesterolemia. It has been used in combination with a statin when the cholesterol-lowering effect of statin treatment alone is not sufficient, or alone in patients unable to take statins. Recent use of Tredaptive in the UK has been less than 3000 patients. A European review of Tredaptive (and similar medicines available outside the UK) was started in December 2012 after new data from a large, long-term study (HPS2-THRIVE) involving over 25 000 patients suggested that the benefits of these medicines did not outweigh the risks. New data show risks outweigh benefits The preliminary results of the study indicated that adding Tredaptive to simvastatin did not provide significant additional benefit in reducing the risk of major vascular events such as heart attack and stroke, compared with statin therapy alone. In addition, a higher frequency of non-fatal but serious adverse events was seen in patients taking Tredaptive with simvastatin, compared with patients taking simvastatin alone. These events included bleeding (intracranial and gastro-intestinal), myopathy, infections and new-onset diabetes. UK healthcare professionals were sent a letter highlighting the new information on Tredaptive in December 2012, and advised not to start any new patients on the drug. In the light of the latest evidence, the benefit-risk balance for Tredaptive is considered negative, and the medicine has been recalled. A letter informing healthcare professionals of this decision was circulated in January 2013.

http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000717/human_med_001034.jsp&mid=WC0b01ac058001d124




http://www.medicinescomplete.com/mc/bnf/current/PHP5713-lenalidomide.htm



http://www.emea.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/12/news_detail_001686.jsp&mid=WC0b01ac058004d5c1




http://www.ctsu.ox.ac.uk/research/mega-trials/hps2-thrive

http://www.ctsu.ox.ac.uk/research/mega-trials/hps2-thrive





Further information: BNF section 2.12: Lipid-regulating drugs http://www.medicinescomplete.com/mc/bnf/current/PHP1700-tredaptive.htm

Advice for healthcare professionals

• Tredaptive has been recalled since 18th January 2013

• Patients currently taking Tredaptive should make a non-urgent appointment to discuss their treatment options with their doctor.

Article citation: Drug Safety Update January 2013 vol 6, issue 6: S1.

S2 Roflumilast (Daxas▼): risk of suicidal behaviour – avoid use in patients with previous or existing psychiatric symptoms and discontinue treatment if new or worsening symptoms are identified

Further information: BNF section 3.3: Phosphodiesterase type-4 inhibitors http://www.medicinescomplete.com/mc/bnf/current/PHP1891-phosphodiesterase-type-4-inhibitors.htm

Roflumilast (Daxas▼) is a phosphodiesterase-type-4 (PDE4) inhibitor used for maintenance treatment of severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis. It is indicated for adult patients with a history of frequent exacerbations as ‘add-on’ to bronchodilator treatment. The recommended dose is one 500 microgram tablet daily. From clinical trial data, roflumilast is known to be associated with an increased risk of psychiatric disorders such as:

o insomnia (in 100 -1000 out of every 10 000 patients) o anxiety (in 10 -100 out of every 10 000 patients) o nervousness and depression (in 1 - 10 out of every 10 000 patients).

Rare instances of suicidal ideation and behaviour, including completed suicide, have been also observed in patients using roflumilast (in 1-10 out of 10 000 patients). A recent review of postmarketing data (unpublished) has found that cases of suicidal behaviour have also been reported postmarketing, and suggests that suicidal behaviour was seen in patients with and without a history of depression, usually in the first weeks of treatment. If patients have existing psychiatric symptoms, or if concomitant treatment is intended with other medicines likely to cause psychiatric symptoms, roflumilast treatment should only be started or continued after careful assessment of the benefits and risks. Advice for healthcare professionals:

• Roflumilast is not recommended for patients with a history of depression associated with suicidal ideation or behaviour.

• Patients and caregivers should be asked to notify the prescriber and their

healthcare provider of any changes to behaviour or mood, and any suicidal ideation. Such symptoms include preoccupation with suicidal thoughts, and self-harm.

• Roflumilast should be discontinued if new or worsening psychiatric symptoms or

suicidal behaviour are identified.

Article citation: Drug Safety Update January 2013 vol 6, issue 6: S2.

http://www.medicinescomplete.com/mc/bnf/current/PHP1700-tredaptive.htm



http://www.medicinescomplete.com/mc/bnf/current/PHP1891-phosphodiesterase-type-4-inhibitors.htm




Other information from the MHRA

O1 Learning about Yellow Card reporting and pharmacovigilance

See: Pharmacovigilance learning module [http://learning.bmj.com/learning/module-intro/.html?locale=en_GB&moduleId=10042344]

We have collaborated with BMJ Learning to develop a multimedia learning module, ‘Pharmacovigilance—identifying and reporting adverse drug reactions’. Using scenario-based learning, supported by video clips, the course explains the importance of continuous monitoring for adverse reactions and the MHRA’s Yellow Card Scheme for reporting suspected adverse reactions; when and how to submit a Yellow Card; and how to keep informed about adverse reactions. This online course is approved for one hour of CPD/CME credit. A certificate of completion is available on passing a short assessment exercise at the end. The course is free of charge and any health professional can participate by registering on the BMJ Learning website.

Article citation: Drug Safety Update January 2013 vol 6, issue 6: O1.

O2 New MHRA Twitter channel on safety of medicines

See: @MHRAmedicines [https://mobile.twitter.com/MHRAmedicines]

The MHRA is pleased to announce the launch of a new Twitter channel, @MHRAmedicines, dedicated to medicines’ safety information. On this channel we will be notifying you when Drug Safety Update is published, and you may also find other safety messages and alerts for medicines and vaccines here too. The medicines safety Twitter channel will work alongside our Devices safety, Herbals safety and Press and Corporate Twitter channels to help our audience stay more up-to-date with targeted information and messages. We will of course continue to publish all of this information on our website and issue email alerts as appropriate. Follow us on Twitter: @MHRAmedicines This channel lists medicines safety updates @MHRAdevices This channel lists devices safety updates @MHRAherbals This channel lists herbal remedy safety updates @MHRAgovuk This is our corporate channel that lists all of the information relating to the work of the MHRA. @MHRApress This channel lists all of our information relevant to the press

Article citation: Drug Safety Update January 2013 vol 6, issue 6: O2.

© Crown Copyright 2013

http://learning.bmj.com/learning/module-intro/.html?locale=en_GB&moduleId=10042344





https://mobile.twitter.com/MHRAmedicines

https://mobile.twitter.com/MHRAmedicines

UHMB NHS Foundation Trust, NHS Cumbria, NHS North Lancs Drugs & Therapeutics Group

Page 1

Minutes of the Drugs & Therapeutics Group Meeting held on Wednesday

2.00pm at the Education Centre, RLI

Present: Ian Chadwick, Chair, Consultant Physician, Medicines Division, UHMBFT Pauline Bourne, Senior Pharmacist Medicines Management, UHMBFT Beverley Phillips, Lead Surgical Pharmacist UHMBFT Julie Lonsdale, Head of Medicines Management, NHS NLancs Tony Rigby, Principal Pharmacist, Clinical Services FGH Victoria Burns, Senior Technician, Medicines Information, UHMBFT – minutes Amjad Cheema, Consultant cardiologist, UHMBFT David Eaton, Consultant Oncologist (item 6.2) Neil Moreland, Consultant Anaesthetist (item 4) Sarah Tait, Pre-registration Pharmacy Student - observing

Action

1. APOLOGIES Hazel Smith, Amanda Pugh.

2. DECLARATION OF CONFLICTING INTERESTS There were no declarations of conflicting interests.

3. MINUTES OF LAST MEETING The minutes of the last meeting were agreed as a correct record.

4. MATTERS ARISING AND ACTION PLAN

See action plan plus the following:

03/09/12 7.1.2 Dexmedetomidine

Neil Moreland, Consultant Anaesthetist attended for this item. Neil had submitted a NPR for dexmedetomidine for sedation in adult ICU patients requiring a sedation level not deeper than arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation Scale 0 to -3)

Neil explained that dexmedetomidine, when compared to conventional sedatives and opiates, has been demonstrated to be associated with both sedative and analgesic sparing effects, reduced delirium and agitation, minimal respiratory depression and predictable and desirable cardiovascular effects. He advised the group that it would be required in 1-2 patients per month for 2-3 days each.

A cost comparison with existing agents was problematic as dexmedetomidine would only be used in patients who were proving difficult to arouse due to delirium or agitation. In these circumstances the use of dexmedetomidine could be associated with cost savings resulting from a shorter duration of mechanical ventilation and hence a reduced length of stay on ICU.

The group agreed to the addition of dexmedetomidine to formulary subject to a Trust protocol for its use being produced and approval by the Surgical

NM/IC


Page 2

Division.

5.NICE TA CHECKLIST AND SPREADSHEET

The group had looked at the spread sheet that had been circulated as an example of recording formulary decisions relating to NICE TA guidance. It was agreed that the D&T group only approve drugs for formulary and is not responsible for implementation of NICE guidance. The group agreed to await completion of the spreadsheet by Cumbria APC before proceeding with this task for UHMBFT.

PB

6. FORMULARY ISSUES

6.1 NEW PRODUCT REQUESTS

6.1.1 Ferinject Approved as second line to Venofer for patients who have asthma or eczema. Will need to go to division for funding approval as there are significant cost implications. 6.1.2 Actilyse Catiflo 2mg For thrombolytic treatment of occluded central venous catheters in haemodialysis patients. Approved add to formulary

VB

6.2 NICE TAGSs & CGs

6.2.1 TA263 Bevacizumab in combination with capecitabine for the first-line treatment of metastatic breast cancer. Not recommended. David Eaton informed the group that this is not being used in the Trust and is not available via the Cancer Drugs Fund. 6.2.2 TA264 Stroke (acute, ischaemic) – alteplase Approved – already on formulary 6.2.3 TA265 Prevention of skeletal-related events in adults with bone metastases from solid tumours- denosumab David Eaton informed the group that denosumab is to replace zoledronic acid for this indication. A discussion took place regarding the possibility of this being administered in general practice. It was agreed that the funding arrangements need clarifying. A shared care guiline has been drafted which is awaiting approval by Lancs medicines management board. DE to highlight cost and administration arrangements to his divisional manager. Add to formulary as RED. 6.2.4 CG149 Antibiotics for early onset neonatal infection Discussed at the antibiotic sub-committee.

VB


Page 3

6.2.5 CG 150 Headaches No implications for formulary 6.2.6 CG 151 Neutropenic sepsis Discussed at the antibiotic sub-committee. No implications for formulary. 6.2.7 CG152 Crohn’s disease Guideline states to assess TPMT activity before offering azathioprine or mercaptopurine and not to offer either drug if TPMT activity is very low or absent. UHMBFT,NHS Cumbria and NHS NLancs shared care guideline states that this test is carried out at consultant discretion. Pauline to check the wording in NICE Clinical Guideline for Rheumatoid Arthritis. Ian to write to the gastroenterologists to inform them of this advice. 6.2.8 CG 153 Psoriasis Vicky to check that Dovobet is on the formulary.

IC VB

6.3 Rolling review of formulary section 4: CNS drugs 4.5 – 4.9 Add CD Trust policy against temazepam formulations Add maximum dose advice against ondansetron Remove Migraleve preparations Remove Epanutin against phenytoin and add Flynn Pharma Remove Dysport brand of botulinum A toxin Add ‘preferred option’ against Xeomin brand Add ‘for previous patients’ against Botox brand Remove the ‘CQ’ from Niquitin patches Add suboxone Remove the 1mg/mL clear methadone liquid

6.4 Digifab Pauline reported that the Digibind in the Trust was going out of date in December 2012. Digifab is not in the BNF 64 but Digibind is. Vicky to inverstigate the availability of digoxin specific antibody.

VB

6.5 Fentanyl with levobupivacaine epidural Beverley informed the group that fentanyl and bupivacaine epidural bags were to be discontinued by Fresenius but due to production problems with the new licence holder Fresenius will continue to manufacture them. The anaesthetists however had indicated their preference to use fentanyl and levobupivacaine as levobupivacaine is less cardiotoxic than bupivacaine. The group approved the use of fentanyl and levobupivacaine 100mL bags by Maternity at both RLI and FGH. Beverley to inform new lead anaesthetist.

BP


Page 4

6.6 NPRS REFERRED TO APCS AWAITING DECISION

Esmya® – ulipristal 5mg for pre-operative treatment of uterine fibroids Mr Bamigboye. Toviaz® – fesoterodine – increased frequency/urgency or UI in patients with overactive bladder. Mr Jain. Fosrenol® – lanthanum powders 750mg and 1000mg. control of hyperphosphataemia in chronic renal failure patients unable to chew or swallow tablets.

6.7 APC DECISIONS

Paliperidone. BLACK in Lancs Tobi Podhaler® RED NLancs AMBER Cumbria Rifaximin. RED Cumbria

6.8 NON-FORMULARY DRUG ISSUES

None highlighted at this meeting

7. PRESCRIBING ISSUES AND GUIDELINES

7.1 NEW ORAL ANTICOAGULANTS IN AF

It was agreed that the Trust should follow the consensus statement issued by the cardiac and stroke networks. Ian agreed to circulate this document to the consultants. The NW transfusion group has drafted guidance for the management of bleeding in patients taking one of the new oral anticoagulants.

IC

7.2 VITAMIN D/FULTIUM D3

Tony circulated the latest draft of the vitamin D guidance which incorporates Richard Neary’s input on monitoring. It was agreed that it needs to make reference to Fultium D3 being available as an option for maintenance therapy and to include the flow chart in the Lothian document in the guidance. It was decided that further discussion was needed on requesting vitamin D levels. Tony to take up with Richard Neary.

TR

7.3 FERINJECT

This item was taken under 6.1 new product requests.

7.4 PHENYTOIN IMPACT ON BUDGET

Pauline reported that Epanutin brand of phenytoin capsules was now marketed by Flynn Pharma and the price has risen a significant amount. It was agreed to ask Dr Nixon for a local view point on prescribing phenytoin and whether it is prescribed by brand name at LTH. The cost pressure in primary care has been noted at Cumbria APC. Kamlesh to have added to the agenda for NLancs/Blackpool APC.

PB


Page 5

7.5 GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH SUBSTANCE MISUE PROBLEMS ON ADMISSION TO ACUTE CARE

It was noted that the guideline still had draft across it. Julie to get this removed and re-send. It was also noted that the guideline now includes a decision tree which it was agreed will be very useful. With regards to patients discharged at short notice where prescribing responsibility may have to remain in secondary care until the community service can take over it was agreed that clients would attend the ward from which they were discharged if supervised consumption is required. Ian to circulate the guideline to consultant colleagues and MAU and place on Heritage. Pauline to inform pharmacists.

JL IC PB

7.6 RISK ASSESSMENT FOR VTE FOR PATIENTS IMMOBILISED WITH PLASTER CASTS

Beverley showed the group the risk assessment that had been produced for patients with lower limb plaster casts. The group agreed that the document needed to be dated and a sentence added regarding bleeding risks and contraindications. It was questioned if the document needed to be signed twice. Beverley agreed to these amendments. To be incorporated into the VTE policy.

BP

8. INTERFACE ISSUES

8.1 ENOXAPARIN AUDIT

Deferred until next meeting as Hazel absent

8.2 INFORMATION SUPPLIED TO G.PS WHEN PATIENTS DISCHARGED ON WARFARIN

Deferred until next meeting as Hazel absent

9 MHRA DRUG SAFETY UPDATES AUGUST 2012 SEPTEMBER 2012

OCTOBER 2012 NOVEMBER 2012

10. MINUTES RECEIVED

10.1 Cumbria APC 11/10/12 10.1.2 NLancs/Blackpool JAPMOG 22/08/12, 24/10/12. 10.1.3 Cumbria Partnership DTC 18/07/12 10.1.4 E Lancs New Meds Sub Group 4/09/11 10.1.5 Lancashire Care DTC 7/08/12, 25/09/12


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10.1.6 Lancashire MMB 4/10/12 plus Terms of Reference for this group, the NICE Sub group and the New Medicines Sub Group. No comments were received on these minutes.

11. ANY OTHER BUSINESS None

12. DATE OF NEXT MEETING The next meeting will be held on Monday 4th February 2013 at 2pm in the Education Centre at WGH.

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Minutes of the Lancashire Medicines Management Board Meeting

held on Thursday 15th November at Preston Business Centre PRESENT: Dr Tony Naughton (TN) Chair Fylde & Wyre CCG Catherine Harding (CH) Head of Medicines Management NHS East Lancashire Elaine Johnstone (EJ) Assocaite Director of Medicines

Management NHS Central Lancashire

Louise Winstanley (LW) CCG Lead Pharmacist and Prescribing Support Team Manager

Fylde and Wyre CCG

Julie Lonsdale (JL) Head of Medicine Management NHS North Lancashire Brent Horrell (BH) Assoc. Head of Med


Pauline Bourne (PB) Senior Pharmacist Medicines Management

University Hospitals of Morecambe Bay

Dr Robert Mitchell (RM) Clinical Lead & Board Member Fylde & Wyre CCG Dr Kamlesh Sidhu (KS) GP Prescribing Lead North Lancs CCG David Jones (DJ) Acting Chief Pharmacist Lancashire Teaching Hospitals

NHS Foundation Trust Dr Sakthi Karunanithi (SK) Dir of Population Health Care/

Public Health Lancashire Lancashire County Council

Mark Collins (MC) Dir of Operations Pharmacy Pennine Lancashire (Local Pharmaceutical Committee)

Sonia Ramdour (SL) Cath Lawless (CL)

Lead Pharmacist Admin Support

Lancashire Care NHS Foundation Trust NHS Blackburn with Darwen

ACTION

1. WELCOME AND INTRODUCTIONS Dr Naughton, Chair of the Fylde and Wyre CCG and nominated Chair of the Lancashire Medicines Management Board on behalf of the Lancashire CCG Network welcomed attendees to the meeting and asked for all organisations to send a representative to the meetings if they are unable to attend.

2. APOLOGIES Apologies were received from: Dr Jim Gardner, Neil Fletcher, Melanie Preston, Lisa Rogan, Dr Catherine Fewster (Sonia Ramdour representing), Lindsay Holden, Alastair Gibson, Dr David Shakespeare, Dr Thomas Mackenzie, Dr Muzaffar, Dr Amanda Doyle, Dr Jane Lofthouse

3. DECLARATIONS OF INTEREST PERTINENT TO THE AGENDA There were no declarations of interest.

4. DECLARATION OF ANY OTHER URGENT BUSINESS PB asked for a matter of urgent business to be deferred until the next meeting.

5. MINUTES OF THE MEETING HELD ON 4TH OCTOBER.

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Where accepted as a true and accurate copy with the exception of: Page 1 Apologies – Should read Dr Manjit Jandu Present - To include David Jones and Dr Jane Lofthouse Page 5 Incorrect spelling of Valvular

6.

MATTERS ARISING: Terms of Reference Action sheet from 4th October – Terms of Reference Page 1 CH reported that the draft TOR have been updated with amendments being in red type. Page 1 Core Business Included MHRA Drug Safety Updates highlighted in red. Page 2 Sub Groups Added Lancashire HIV Formulary Group Page 3 Members should: Added to review the agenda and supporting papers in advance of the meeting and added a clause around confidentiality. Decision Making: Added content of which to be considered and agreed by the Medicines Management Board. Added voting will be on the basis of one vote per organisation with the Chair having the casting vote. Reference to reporting arrangements through the PCT Cluster Board had been removed. Further Comments: SK asked for there also to be added and considered recommendations from the Joint Pharmaceutical Needs Assessment Partnership.

Lancashire Medicines Management Board Terms of Reference 15 November 2012.docx

LW suggested that discussion of the draft Terms of Reference be deferred pending further discussion to include absent members of the group whom she felt would be able to add to the discussion. A lengthy discussion was had on the governance arrangements for the Board in respect of processes for reaching decisions and making recommendations, particularly in respect of CCGs. In summary it was agreed that there needed to be more clarity on how recommendations would be ratified within individual organisational governance arrangements. EJ said that local arrangements would sit outside this group. Draft Over-arching policy / procedure for the Lancashire MMB A draft overarching policy document for the priority setting of medicines and operation of the Lancashire Medicines Management Board was presented by CH. The document was based on a model policy currently operating in Pennine Lancashire that had been revised and updated to make it relevant to CCGs and the Lancashire Medicines Management Board. It was suggested that reference to the NHS Constitution be included. SK highlighted the similarity with the Individual Patient Activity / Individual Funding Request work and the importance of it being aligned. The Lancashire Principles for the Commissioning of Health and Healthcare developed with leadership from public health were included in Appendix 2 of the policy. It was suggested that

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Appendix 2 should be specifically referenced as the Ethical Framework. In view of a number of organisations not being represented at the meeting the Chair suggested that members be provided with further opportunity to comment on the draft policy before presenting the policy and group Terms of Reference for consideration by the meeting of the Lancashire CCG Network on the 20th December. ACTION: Members to forward further comments on the Terms of Reference and policy document to Catherine Harding by the 29th November prior to further consideration by the Lancashire CCG Network at its meeting on the 20th December. To Note: MC joined the meeting

ALL

7.

Sub Group Terms of reference – Presented by Catherine Harding – Draft Terms of Reference for the New Medicines and Treatments and NICE sub-groups were presented by CH. LW proposed that a task and finish group should be set to up to look at the Terms of Reference and policy document at a CCG level. BH expressed his concern that clarity was required on how CCG’s would consider and act on recommendations from the Lancashire Medicines Management Board. TN indicated that he had spoken with the Chair of the Lancashire CCG Network, Dr Chris Clayton (BWD CCG) at length who provided him with assurance that the Lancashire MMB has the support of the Lancashire CCG Network. ACTION: As a CCG representative, LW to organise and lead on a task and finish group inclusive of CCG clinical members to provide CCG leadership in the development of a transition plan outlining the necessary actions and processes required to enable a collaborative Lancashire commissioner approach to medicines prioritisation and decision making in the new system. The outputs from this work would be taken to the Lancashire CCG Network for consideration.

LW

8.

Cardiac & Stroke Networks and medicine management collaborative processes – Deferred. To be considered in the broader discussion on the Board Terms of Reference and those of its sub-groups.

9.

High Cost drugs – Update paper to Lancashire MMB – Presented by Catherine Harding A report prepared by Richard Lee and Diane Eden from the Cumbria and Lancashire NHS Collaborative Business Services was presented by CH. At present it is estimated that £46.5 million is being spent by Lancashire and Cumbria PCTs on high cost drugs, with anti-TNF drugs being one of the largest areas of spend. From April 2013 CCGs will be responsible for the commissioning and funding of those high cost drugs used within services and treatment pathways commissioned by CCGs. High cost drugs had been a collaborative commissioning workstream and the

4

report provided an update on progress and achievements to date. CH highlighted the recommendations and what was being asked of the Lancashire MMB. The Board agreed to:

support and oversee a continued collaborative approach to the commissioning and use of high cost drugs and homecare medicines as an already established QIPP workstream

(with reference to the role of the Lancashire MMB in formulating recommendations for the use of medicines across Lancashire and further discussion as per items 6 and 7) act as the forum for consensus decision making in relation to policies or proposals for high cost drugs and homecare medicines, making recommendations to CCGs and providers for their use

The ongoing work with the rheumatologists to agree common treatment pathways for the use of the anti-TNFs and proposed agenda for a meeting of the Rheumatology Alliance and medicines management representatives to be held on the 23rd November were noted. ACTION: Richard Lee to be asked to provide an update report to a future meeting of the Lancashire MMB on this programme of work. Proposed commissioning policies for the use of anti-TNFs in rheumatology treatment pathways recommended by the Rheumatology Alliance and medicines management to be considered by the Lancashire MMB as they are developed.

RL

10.

Horizon Scanning Briefing Report: Presented by Elaine Johnstone EJ presented the briefing report and asked for the information not to be shared any wider as the report included confidential information – namely it highlights medicines that are expected to be launched during 2013/2014 as well as new indications for established medicines that are likely to have a significant impact for CCGs. The report excluded those medicines known to be commissioned by the NHS CB in future i.e. chemotherapy. Members of the group sought clarity on the methodology for determining the priority score and the desire for more detailed financial information to assess financial impact. It was noted that this was an early version of the report pending the release of financial information nationally, at which point it would be updated. The population figures needed amending to reflect CCG populations rather than PCT. It was agreed that the New Medicines and Treatments working group should be asked to utilise the horizon scanning report as a basis for prioritising a programme of work, making recommendations to the Lancashire MMB for consideration. ACTION: New Medicines and Treatments sub-group to be asked to formulate a prioritised work programme, to proactively consider new medicines coming to market and new indications for existing medicines prior to launch.

EJ

5

11.

Aflibercept (Eylea®) Briefing Report – Presented by Elaine Johnstone A report prepared by Richard Lee was presented by EJ. A new treatment for AMD (aflibercept) is expected to receive a UK marketing authorisation in December 2012. Its utilisation within the treatment pathway for AMD in suitable patients has the potential to release savings and provider capacity across the NHS in Lancashire. Aflibercept has not at present been considered by NICE and there is an opportunity for a local decision to be taken. The Lancashire MMB was asked to endorse a dialogue with ophthalmologists on behalf of CCGs to develop a clinical pathway including aflibercept as a treatment option for wet AMD, and this was supported. ACTION: Task and finish group working with ophthalmologists to be established to review the evidence for aflibercept and make recommendations to the Lancashire MMB. New Medicines and Treatments Group to oversee the programme of work.

EJ

12.

Fingolimod (▼Gilenya®) for the treatment of multiple sclerosis– Presented by Brent Horrell BH briefed the group on the position statement for the use of Fingolimod. Fingolimod is licensed as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following adult patient groups: - Patients with high disease activity despite treatment with a beta-interferon. These patients may be defined as those who have failed to respond to a full and adequate course (normally at least one year of treatment) of beta-interferon. Patients should have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2-hyperintense lesions in cranial MRI or at least 1 Gadolinium-enhancing lesion. A “non-responder” could also be defined as a patient with an unchanged or increased relapse rate or ongoing severe relapses, as compared to the previous year. or - Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI. Fingolimod is recommended by NICE (TAG 254, April 2012) as an option for the treatment of highly active relapsing–remitting multiple sclerosis in adults, only if:

they have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon, and

the manufacturer provides fingolimod with the discount agreed as part of the patient access scheme.

NICE has been asked to clarify whether the recommendation for the use of fingolimod extends to people with relapsing remitting multiple sclerosis who are currently receiving treatment with glatiramer acetate, and who experience an unchanged or increased relapse rate or ongoing severe relapses

6

compared with the previous year. NICE understands that this query refers to the note included in the ‘Posology and method of administration’ section of the summary of product characteristics for fingolimod that states that ‘patients can switch directly from beta interferon or glatiramer acetate to fingolimod provided there are no signs of relevant treatment–related abnormalities’. In line with the referral received from the Department of Health, NICE appraised fingolimod with reference to the therapeutic indication specified in the marketing authorisation; that is ‘Patients with high disease activity despite treatment with a beta-interferon’. The manufacturer provided no submission for the other population in the marketing authorisation. Considering that NICE cannot produce guidance for a medicine outside of the licensed indication included in the marketing authorisation, the recommendation for the use fingolimod does not extend to people currently receiving glatiramer acetate. NICE were unable to make a specific recommendation about the use of fingolimod in patients with rapidly evolving severe (RES) relapsing–remitting

multiple sclerosis because the manufacturer had not submitted an analysis of fingolimod compared with natalizumab in this population. NICE acknowledged the clinical specialists’ disappointment at this since the clinician view was that fingolimod would provide the greatest benefit to people with rapidly evolving severe relapsing-remitting multiple sclerosis because they currently have very few treatment options. A position statement for the local commissioning of fingolimod had been developed by Lisa Rogan, Chair of the East Lancashire health economy New Medicines and Treatments Group in consultation with local clinical specialists from Lancashire Teaching Hospitals NHS Trust. The position statement was based on work produced by the Greater Manchester Medicines Management Group’s Neuroscience Network. The position statement recommends as a treatment option the use of fingolimod in accordance with NICE guidance for those patients with highly active relapsing-remitting multiple sclerosis who fail on beta-interferon. It also permits the use of fingolimod for those patients with highly active relapsing-remitting multiple sclerosis who fail on glatiramer acetate (out of licence and not considered by NICE), and those patients with RES who are either not suitable for natalizumab or who fail on natalizumab (within licence but not considered by NICE). Summary of position statement:

• Patients who have rapidly evolving severe (RES) relapsing remitting MS but are not considered suitable for natalizumab (Tysabri®) because of the clinical concerns (risk stratification) about the possibility of developing progressive multifocal leukoencephalopathy (PML); or

• Patients who fail on natalizumab (Tysabri®) due to neutralising antibodies and, or anaphylactic reaction; or

• Patients who fail on natalizumab (Tysabri®) due to relapses; or • Patients who fail on beta-interferon (Avonex, Betaferon/Extavia, Rebif

22/44) and/or glatiramer acetate (Copaxone®) who have had more relapses than the previous year; or

• Patients who fail on a beta-interferon (Avonex, Betaferon/Extavia, Rebif 22/44) and/or glatiramer acetate (Copaxone®) due to inability to self-inject, lack of adequate injection sites or skin necrosis; or

• Patients who develop high and sustained levels of neutralising antibodies to a beta-interferon (Avonex, Betaferon/Extavia or Rebif

7

22/44) and also fail on glatiramer acetate (Copaxone®) due to inability to self-inject, lack of adequate injection sites or skin necrosis.

The Board heard that the sub-group of patients using fingolimod was likely to be low and any increased costs would be offset against administration costs associated with natalizumab (for patients with RES). Where fingolimod was to be offered to patients who had failed on glatiramer acetate, the incremental cost per annum across the Lancashire CCGs was in the order of £25,000. (It was noted that the total commissioner annual spend across Lancashire on drug treatments for MS was circa £900,000. The cost implications of implementing the NICE guidance on fingolimod was in the order of £75,000 per annum).

Fingolimod position statement October 2012.doc

The position statement was supported by the meeting, but LW suggested that CCGs would not approve in the absence of NICE and concluded that the minutes needed to be supplemented by additional information explaining the reasoning for the decision so that CCGs to have confidence in endorsing the recommendations clinically.

13.

Joint Formulary for Psychotropic Medication – Presented by Sonia Ramdour The joint work of the Lancashire Care Foundation Trust (LCFT) and PCTs across Lancashire in agreeing a joint prescribing formulary for psychotropic medication was presented by Sonia Ramdour, Lead Pharmacist at LCFT and Julie Lonsdale, Head of Medicines Management at North Lancashire PCT. The Lancashire Medicines Management Board was asked to endorse the joint formulary. For clarity, BH suggested that a clarifying statement be included in the formulary introduction explaining that all medicines available for prescribing in the BNF are listed with those medicines not approved for use being indicated as non-formulary or black traffic lighted. Reference was made to shared care prescribing and shared care protocols being poorly agreed with primary care and inadequately shared. SR advised that shared care documents have been agreed by all Lancashire PCTs except for Blackpool and expressed a desire to progress shared care work in Blackpool. To Note: SK left the meeting. Approval was given for the joint formulary – Discussion around the document and where it would sit was discussed as it was agreed that it would useful to share on a national basis.

Joint Formulary -Updated Nov 2012.doc

14.

Shared Care Guidelines for Immunosuppression following Renal

8

Transplant. – Sirolimus, Prograf, Myfortic, Ciclosporin, Cellcept, Azathioprine and Advagraf - Presented by David Jones A series of updated shared care protocols for the prescribing of immunosupressants following renal transplant were presented by DJ for approval. Manchester Royal Infirmary supply for three months following transplant before passing responsibility to the LTH renal team. Once the patient is stable the renal team at LTH will request that the GP prescribes. Biochemical monitoring is undertaken by the hospital; GP monitoring includes a physical health check, including BP measurement. LW reported that work is on-going developing shared care guide lines across Lancashire. Concern was raised that the shared care guidelines with the same provider Trust should be different across Lancashire. It was agreed that there should only be one document for each drug per speciality and provider. JL asked for the wording under “Primary Care Responsibilities” implying GPs have no option but to take on shared care, and the wording that states “GPs must respond promptly to requests” to be reviewed and amended. ACTION: DJ to incorporate the comments into the final version adopted into practice.

DJ

15.

Recommendations for the Prescribing of High Fluoride Toothpaste in Primary Care - Presented by Catherine Harding The Chair of the Lancashire MMB had been approached by the Chair of the Lancashire Dental Transformation Board requesting that advice previously issued to the East Lancashire Medicines Management Board on high fluoride-content toothpaste and subsequent agreement of a prescribing recommendation be considered for adoption across Lancashire. CH asked for approval from the board for recommendations from the Lancashire Dental Transformation Board for the prescribing of high fluoride toothpaste across Lancashire. SR suggested that there could be implications from LCFT in relation to Trust provided community dental services and suggested that it needed consideration by the LCFT Drug and Therapeutics Committee. ACTION: SR to take the proposal to the LCFT D&T Committee meeting on the 27th November to consider any implications for LCFT provided community dental services. Following confirmation that the view was supported by GDPs across Lancashire the recommendations were approved for adoption across Lancashire in relation to General Dental Practitioners.

Recommendations for the prescribing of high fluoride toothpaste.doc

MC indicated that within community pharmacy increasing volumes of high fluoride toothpaste were being prescribed. The Chair enquired how the prescribing of General Dental Practitioners was monitored. It was noted that at present there is no PACT data for dentists. ACTION: CH to pick up the issue of monitoring of the guidance and prescribing with the Dental Transformation Board.

SR

CH

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16.

Shingles (herpes zoster) Vaccine – Presented by Catherine Harding CH presented a position statement on the prescribing and supply of herpes zoster vaccine for consideration. It was noted that the Department of Health was considering the introduction of a national herpes zoster immunisation programme in persons aged 70 to 79 years pending an evaluation of the cost-effectiveness. A licensed herpes zoster vaccine is available and prescribable on FP10 on a case by case basis. The estimated cost of implementing a herpes zoster vaccination programme in Lancashire outside of a national immunisation programme was estimated to cost in the region of £13 million. Having sought advice from the HPA, the recommendation was that until the Department of Health announces the introduction of a national herpes zoster immunisation programme, the prescribing and administration of herpes zoster vaccine in primary care in Lancashire could not be supported. The position statement was approved by the Board.

Recommendations for the prescribing of herpes zoster vaccine.doc

SK suggested involvement of the HPA in communicating the message to stakeholders as a co-signatory on any correspondence.

DATE AND TIME OF NEXT MEETING Thursday 13th December 9.30 – 11.30 A.M. Meeting Room 2, Preston Business Centre. link to venue directions

http://www.lancsteachinghospitals.nhs.uk/trust-information/find-us/directions-to-smrc.html

FUTURE MEETINGS Future meeting dates would be scheduled for the 2nd Thursday of the month at 9.30am, to be held in Meeting Room 2, Preston Business Centre. 9.30 am – 11.30am (All Thursdays) in Meeting Room 2, Preston Business Centre 13th December (2012) 10th January (2013) 14th February (2013) 14th March (2013) 11th April (2013) 9th May (2013) 13th June (2013) 11th July (2013) 8th August (2013) 12th September (2013) 10th October (2013) 14th November (2013) 12th December (2013)



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ACTION SHEET FROM THE LANCASHIRE MEDICINES MANAGEMENT BOARD

THURSDAY 13th November 2012

MINUTE NUMBER

DECSRIPTION ACTION DATE

2012/006 NICE consultation the development and updating of local formularies CH to update the Draft Terms of Reference to address gaps highlighted by the NPC consultation document Operational policy for the Lancashire Medicines Management Board to be drafted and considered at the next meeting

CH

CH

Action complete Action complete

2012/007 Lancashire wide prescribing formulary: progress report and next steps Products from the work of the formulary task group to be circulated to members Options paper for the communication of Lancashire Medicines Management Board decisions to be brought back to a future meeting Terms of Reference for the Lancashire MMB to be updated following discussion and re-circulated Terms of Reference for the sub-groups to be drafted and circulated for comment

BH

CH

CH

CH

Oct 12 Dec 12 Action complete Action complete

2012/009 Lancashire HIV prescribing formulary HIV formulary group to be recognised as a sub-group of the Lancashire Medicines Management Board in the edited ToR

CH

Action complete

2012/010 Guidelines for the management of patients with substance misuse problems on admission to acute care Provider Trusts to consider the adoption and/or adaptation of the guidance for use within their own organisations

Trust Reps

Nov 12

2012/018 Draft Terms of Reference and Overarching Policy Document Members to forward further comments on the Terms of Reference and policy document to Catherine Harding by the 29th November prior to further consideration by the Lancashire CCG Network at its meeting on the 20th December.

ALL

Nov 12

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2012/019 Sub group Terms of Reference LW to organise and lead on a task and finish group inclusive of CCG clinical members to provide CCG leadership in the development of a transition plan outlining the necessary actions and processes required to enable a collaborative Lancashire commissioner approach to medicines prioritisation and decision making in the new system. The outputs from this work would be taken to the Lancashire CCG Network for consideration.

LW

December 12

2012/022 Horizon scanning briefing report New Medicines and Treatments sub-group to be asked to formulate a prioritised work programme, to proactively consider new medicines coming to market and new indications for existing medicines prior to launch.

EJ

January 13

2012/023 Aflibercept briefing report Task and finish group working with ophthalmologists to be established to review the evidence for aflibercept and make recommendations to the Lancashire MMB. New Medicines and Treatments Group to oversee the programme of work.

EJ

December 12

2012/026 Shared care guidelines for immunosupressants following renal transplant DJ to incorporate comments into the final version adopted into practice.

DJ

December 12

2012/027 Recommendations for the Prescribing of High Fluoride Toothpaste in Primary Care SR to take the proposal to the LCFT D&T Committee meeting on the 27th November to consider any implications for LCFT provided community dental services. Arrangements for monitoring the application of the guidance to be queried with the Lancashire Dental Transformation Board

SR

CH

November 12 November 12

1

Minutes of the Lancashire Medicines Management Board Meeting

held on Thursday 13th December at Preston Business Centre PRESENT: Dr Tony Naughton (TN) Chair Fylde & Wyre CCG Catherine Harding (CH) Head of Medicines Management NHS East Lancashire Elaine Johnstone (EJ) Associate Director of Medicines


Louise Winstanley (LW) CCG Lead Pharmacist and Prescribing Support Team Manager

Fylde and Wyre CCG

Julie Lonsdale (JL) Head of Medicine Management NHS North Lancashire Lisa Rogan (LR) Head of Medicines

Commissioning (designate) East Lancashire and Blackburn with Darwen CCGs

Cath Fewster (CF) Chief Pharmacist/Accountable Officer

Lancashire Care Foundation Trust

Neil Fletcher (NF) Clinical Director of Pharmacy East Lancashire Hospitals NHS Trust

Dr Li Kam Wa (LWK) Consultant General Medicines/ D & T Chair

Blackpool teaching Hospitals

Pauline Bourne (PB) Senior Pharmacist Medicines Management

University Hospitals of Morecambe Bay

Dr Robert Mitchell (RM) Clinical Lead & Board Member Fylde & Wyre CCG Dr Kamlesh Sidhu (KS) GP Prescribing Lead Lancashire North CCG David Jones (DJ) Acting Chief Pharmacist Lancashire Teaching Hospitals

NHS Foundation Trust Lindsay Holden (LH) Head of Medicines Management NHS Blackburn with Darwen Linda Bracewell (LB) Community Pharmacist Lancashire Pharmacy

Transformation Board Melanie Preston (MP) Head of Medicines Management Blackpool PCT Alastair Gibson (AG) Director of Pharmacy Blackpool Teaching Hospitals Dr Muzaffar GP Lead Blackburn with Darwen CCG Dr Jane Lofthouse GP Lead Chorley and South Ribble CCG Cath Lawless (CL) Administrator NHS Blackburn with Darwen ACTION

2012/028 WELCOME AND INTRODUCTIONS

2012/029 APOLOGIES Apologies were received from: Dr Thomas Mackenzie, Dr Sakthi Karunanithi, Dr Pervez Muzzafar, Dr Shakespeare, and Mrs Helen Lowey

2012/030 DECLARATIONS OF INTEREST PERTINENT TO THE AGENDA There were no declarations of interest.

2012/031 DECLARATION OF ANY OTHER URGENT BUSINESS There were no declarations of urgent business.

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2012/032 MINUTES OF THE MEETING HELD ON 15th NOVEMBER Were accepted as a true and accurate record with the exception of: Page 1 Apologies – To include Dr Li Kan Wa Page 8 Shared Care Guidelines for Immunosuppression following Renal Transplant – LW asked for the wording on the end paragraph to be corrected as she did not say that work is on-going in developing the shared care guidelines.

2012/033

MATTERS ARISING: Action List 2012/007 – Lancashire wide prescribing formulary options paper – EJ suggested deferring further discussion on the formulary work until further clarity was obtained. Options paper for the communication of Lancashire Medicines Management Board messages – CH suggested this piece of work be deferred pending clarity on the supporting mechanisms for the work of the Board and local decision making. 2012/019 – Sub group Terms of Reference – to be picked up through the main agenda. 2012/022 – Horizon Scanning Briefing Report – The horizon scanning briefing report was discussed at the preceding week’s meeting of the New Medicines and Treatments group. The group was on track to deliver recommendations to the February meeting of the Board. 2012/023 – Aflibercept briefing report – LR provided feedback from the New Medicines and Treatments group meeting. Richard Lee had been asked to undertake further work looking at Lucentis® and aflibercept. CH provided feedback from the Lancashire Eye Care Board who had been asked to consider whether they had a role in this piece fo work. The Eye Care Board had advised of the relevant clinicians to be included in the work, namely Mrs S Abu-Green from Royal Blackburn Hospital, Mr Khalil from Blackpool Victoria Hospital and Mr Simon Morgan from Morecambe Bay Hospitals. NF suggested that Dr A Vijaykumar (East Lancashire Hospitals Trust) also be included in the discussion. 2012/026 – Shared Care Guidelines for Immunosupressants – DJ advised that comments had been fed back to the LTH renal group and final versions would be circulated in due course. 2012/027 – Recommendations for the Prescribing of High Fluoride Toothpaste – The recommendations had been discussed at the LCFT D&T meeting and the principle of dental prescribing supported. Further understanding of the budgetary implications for dental prescribing post April 2013 was needed.

2012/034

Governance arrangements for the Lancashire MMB

3

Feedback from Transition Meeting LW reported that a meeting with ten representatives from the various organisations met at Jubilee House on 11th December. Topics of discussion included: General concensus and the way forward – The rational for the group – Change in the system – Clear rationale for tertiary services – Decision making versus recommendations – LMMB can only make recommendations – 2 levels of meetings instead of 3 – How do we incorporate new drugs into the system. An options paper prepared by LR had been circulated at the meeting. LW also produced a diagram from the meeting outlining the different areas that would be fed back to the various groups and also to the board. Updated Terms of Reference for the East Lancashire MMB had been circulated and discussed at the meeting. LR commented that the ToR for the Lancashire MMB duplicated those of the East Lancashire MMB. It was suggested that the ToR for the New Medicines and NICE groups be incorporated into the ToR for the Lancashire MMB in preference to having sub-groups. EJ commented that as yet the operational details are still up for discussion and that the paper has not been circulated. EJ said that the New Meds Sub Group would be the task and finish group where items are brought to the group and then referred back to LMMB. It was agreed that the 10th January meeting would be a working group meeting to finalise the Terms of Reference and operational arrangements for the Lancashire MMB. The Chair emphasised the importance of representation from all CCGs. ACTION:

LW to finalise the paper from the meeting held on the 11th December and share with the full membership early w/c 17th December for comment

Board members to forward comments back to LW

LW

ALL

2012/036

Commissioning of High Cost Drugs Two recent developments relating to the commissioning of high cost drugs and associated services were outlined by CH. The first related to changes to commissioning arrangements, with many high cost drugs being commissioned in future by the NHS Commissioning Board and the remainder being commissioned by CCGs. The paper presented provided an indication of those medicines for which responsibility for commissioning would rest with the CCGs. Although the list was shorter (compared to the NHS CB) the volume of usage and financial implications were significant. National Homecare Medicines Review and Implementation – The second development was the recent publication from the Department of Health of guidance on achieving savings from high cost drugs that made reference to gain share agreements between providers and commissioners. CH asked for the Board to mandate to a small working group to take this forward. NF commented that management of high cost drugs involved significant amounts of work for providers without the necessary resources to deliver. AG supported the establishment of a small group to develop principles. ACTION:

4

CH and AG to consider the development of draft principles, making recommendations to the Board

CH/AG

2012/037

Traffic Light Drug Classification (NHS Leeds) Resources supporting the implementation and communication of a Traffic Light Scheme for prescribing responsibility developed by NHS Leeds were shared with the Board. CH suggested the resources could be adapted for use across Lancashire. Blackpool, Fylde and Wyre CCGs were supportive of the approach; LR indicated support for the adoption of principles across Lancashire but cautioned the need for local consideration. TN commented on the problems that may be encountered by providers dealing with different policies in different areas. This was confirmed by CF who also recognised the right of individual GP prescribers not to prescribe. There was a lengthy discussion around amber drugs and also the grey and black classification and that it would be difficult to adopt because of the difference in the areas of demographics. It was noted that the classification system used in the Leeds document would need to be amended to reflect the definitions used in Lancashire. PB suggested considering a consensus Lancashire view for new drugs but commented there may be problems reviewing historically agreed arrangements. LB highlighted the difficulty that patients have navigating their way through the system e.g. people with dementia having to get taxis to attend clinics to obtain medication. LB indicated that in reality the patient would present to the GP where there were problems. The principle of a Lancashire approach to the RAG classification system and recommendations for new medicines was supported. ACTION: CH to edit the Leeds document based on the discussion and bring back to a future meeting for final comment and endorsement

CH

2012/038

Guidance on antiplatelet prescribing post stroke or TIA A paper recommending the use of clopidogrel as the first-line treatment option for secondary prevention following a TIA was presented by LR. This was based on advice from the Royal College of Physicians in the recent version of their stroke guidelines and reflected current specialist practice as evidenced by a letter from the Cardiac Network. It was acknowledged that this was an unlicensed use of clopidogrel and therefore it had not been considered by NICE but it was recommended based on the following basis:

TIA and ischaemic stroke are different manifestations of the same disease

Clopidogrel is better tolerated than aspirin and dipyridamole with the potential for improved patient concordance and treatment outcomes

Lower acquisition cost for clopidogrel (compared to aspirin and dipyridamole)

It reflects current specialist clinical practice

The proposal was supported. In view of clopidogrel being used outside of its product licence for this indication the importance of informed patient consent was discussed. It was agreed that a leaflet given to patients to explain the terminology would be useful. Further comments from the group were that the clinician who initiated the treatment should explain to the patient. CF commented that LCFT already has a leaflet for patients on unlicensed medicines which she agreed to share with members of the Board.

5

ACTION:

CF to share the LCFT off licence leaflet with the Board

LR to ask the Cardiac Network to devise a patient information leaflet

CF LR

2012/039

Proposal to develop a common set of medicines management quality indicators EJ asked the Board to consider the recommendations outlined in the document as an example of partnership working across Lancashire. The Lancashire MMB had the expertise to make recommendations to commissioners on quality indicators for medicines management and medicines optimisaiton. CF queried whether it was outside the scope of the Lancashire MMB. It was suggested that the CCG Network be asked for a view. EJ agreed to take the paper back.

2012/040

Guidance for Prescribing in primary care across Lancashire CH asked members of the board to consider whether there was support for the development of guidance covering the principles of good practice in prescribing and medicines handling for primary care. The decision from the board was to support the development of Lancashire guidance and asked CH to lead on the piece of work and bring back for consideration at a future meeting. ACTION: CH to lead the development of Lancashire guidance covering the principles of good practice in prescribing and medicines handling for primary care

CH

2012/041

Policy for the prescribing of Vitamins, Minerals, Supplements, Herbal and Homeopathic Medicines without a Product Licence The policy developed for use across the East Lancashire health economy was shared with members of the Board with a view to it being considered by other stakeholder organisations for local adoption or adaptation. Comments from the group were that GPs would find the guidance useful. ACTION: Lancashire MMB members to consider adopting the policy within their own organisations and feedback to a future meeting the outcome of local discussion.

ALL

DATE AND TIME OF NEXT MEETING Thursday 10TH January 2013 - 9.30 – 11.30 A.M. Meeting Room 2, Preston Business Centre. link to venue directions


FUTURE MEETINGS Future meeting dates would be scheduled for the 2nd Thursday of the month at 9.30am, to be held in Meeting Room 2, Preston Business Centre. 9.30 am – 11.30am (All Thursdays) in Meeting Room 2, Preston Business Centre 14th February (2013)



6

14th March (2013) 11th April (2013) 9th May (2013) 13th June (2013) 11th July (2013) 8th August (2013) 12th September (2013) 10th October (2013) 14th November (2013) 12th December (2013)

7

ACTION SHEET FROM THE LANCASHIRE MEDICINES MANAGEMENT BOARD

THURSDAY 15th December 2012

MINUTE NUMBER

DECSRIPTION ACTION DATE

2012/007 Lancashire wide prescribing formulary Options paper for the communication of Lancashire MMB recommendations to be brought back to a future meeting

CH

Dec 12 (deferred

pending ToR discussion)

2012/021 High Cost Drugs QIPP L3 workstream Richard Lee to be asked to provide an update report to a future meeting of the Lancashire MMB on the programme of work

RL

March 2013

2012/023 Aflibercept Briefing Report Pathway development to include input from Mrs S Abu-Green from Royal Blackburn Hospital, Mr Khalil from Blackpool Victoria Hospital and Mr Simon Morgan from Morecambe Bay Hospitals. NF suggested that Dr A Vijaykumar (East Lancashire Hospitals Trust).

RL / LR

Ongoing

2012/034 Governance Arrangements for LMMB Paper from 11th December meeting to be shared. Board members to provide feedback

LW ALL

Dec 12

2012/036 National Homecare Medicines Review and Implementation Draft principles and recommendations to be developed for consideration by a future meeting of the Board

CH/AG

Feb 12

2012/037 Traffic Light Drug Classification Leeds document to be edited based on the meeting discussion and bring back to a future meeting for final comment and endorsement

CH

Feb 12

2012/038 Guidance on antiplatelet prescribing LCFT unlicensed medicines patient information leaflet to be shared with the Board Cardiac Network to be asked to develop a patient information leaflet

CF

LR

Jan 12

Jan 12

2012/040 Guidance for Prescribing in primary care across Lancashire Lancashire guidance covering the principles of good practice in prescribing and medicines handling for primary care to be developed

CH

March 12

8

2012/041 Policy for the prescribing of Vitamins, Minerals Supplements, Herbal and Homeopathic Medicines without a product licence Board members to consider adoption / adaptation of the policy for local use and feedback local decision to a future meeting

ALL

Feb 12

LOTHIAN FORMULARY COMMITTEE

FINAL – 19th December 2012 [email protected]

FORMULARY COMMITTEE

Minutes of the Formulary Committee meeting held on 19th December 2012 from 2.00pm – 3.15pm

in Room 004, Ground Floor, Pentland House

Present: Dr E Brown Consultant Oncologist, Western General Hospital J Carson Lead Directorate Pharmacist, Royal Infirmary of Edinburgh Dr J Forbes Formulary Committee Co-Chair and Reader in Health

Economics, University of Edinburgh Dr H Gillett Consultant Gastroenterologist, St John’s Hospital Dr S Hurding General Practitioner, NHS Lothian Dr W Jamieson General Practitioner, Lothian S Kerr Lead Pharmacist, Western General Hospital Professor S Lawrie Formulary Committee Co-Chair and Professor and Honorary

Consultant Psychiatrist, Royal Edinburgh Hospital (in the chair)

J Pearson Formulary Pharmacist, NHS Lothian L Shaw Lead Directorate Pharmacist, Royal Infirmary of Edinburgh T Slaughter Clinical Effectiveness Pharmacist, North Cumbria Medicines

Management Group G Todd Lead Pharmacist, Royal Edinburgh Hospital and Roodlands

Hospital Dr D Wilks Consultant in Infectious Diseases, Western General Hospital In attendance: Z Stofankova Formulary Committee Administrator T Duff Pharmacist, Medicines Information, Royal Infirmary of

Edinburgh Apologies for absence: J Bradie Clinical Nurse Manager, Royal Infirmary of Edinburgh Dr J Dear Consultant Clinical Pharmacologist, Royal Infirmary of

Edinburgh Dr S C Hornibrook General Practitioner, Lothian L Leitch Formulary Pharmacist, NHS Borders I Mohammed Clinical Effectiveness Pharmacist, NHS Fife Dr R Williams General Practitioner, Lothian Welcome: The Chair welcomed Tracy Duff, Pharmacist, Royal Infirmary of Edinburgh as an observer at the meeting and members introduced themselves in turn. Declarations of interest: The Chair reminded members to declare any interests in any of the products to be discussed.



1. Minutes of the previous meeting held on 14th November 2012 1.1 The minutes of the meeting of 14th November 2012 were approved as an accurate

record of that meeting. 2. Matters arising from previous minutes None.

3. SMC Recommendations

3.1 fesoterodine (Toviaz®) 3.1.1 The committee noted and discussed the previously circulated submission and

SMC report. One declaration of interest (personal, specific) was included with the submission and noted by the committee. A committee member also noted a non-personal, non-specific interest.

3.1.2 The committee noted the FAF1 submission for the use of fesoterodine (Toviaz®)

for treatment of the symptoms (increased urinary frequency and/or urgency and/or urgency incontinence) that may occur in patients with overactive bladder syndrome (OAB.)

3.1.3 It was noted that a local Lothian protocol has not been developed. 3.1.4 It was noted that currently oxybutynin and solifenacin are the first-line treatment

options and the clinical team has suggested that they would use fesoterodine as a third-line therapy agent.

3.1.5 The committee noted that the applicants propose that due to the refractory nature of OAB it is important to have more than 2 treatment options available to avoid unnecessary hospital referral. It is suggested that current practice in Lothian is to refer after using the 2 products currently on formulary which incurs a referral cost for patients to receive a third-line agent.

fesoterodine fumarate 4mg and 8mg prolonged release tablets (Toviaz®) No. 480/08

ADVICE: following a full submission: fesoterodine fumarate (Toviaz®) is accepted for restricted use within NHS Scotland. Indication under review: For treatment of the symptoms (increased urinary frequency and/or urgency and/or urgency incontinence) that may occur in patients with overactive bladder syndrome. Fesoterodine is effective in reducing symptoms associated with overactive bladder syndrome without a neurological cause and was of equivalent efficacy to a comparator antimuscarinic agent in one study. Fesoterodine is associated with adverse effects typical of antimuscarinic agents used in this condition. It is restricted to second-line use as there are cheaper antimuscarinics available that would normally be used as first-line agents.



3.1.6 It was noted that the application is not in line with the SMC advice which relates to the use of fesoterodine in a second-line setting and there is no evidence presented for the use of this drug as a third-line agent.

3.1.7 An application was discussed previously in May 2010 as ‘Not preferred’ in Lothian as suitable alternatives exist.

3.1.8 The committee agreed to Not Include fesoterodine (Toviaz®) on the LJF because the NHS Lothian decision is that the medicine does not represent sufficient added benefit to other comparator medicines to treat the condition in question.

ACTION: SL/JP 3.2 tenofovir (Viread®) 3.2.1 The committee noted and discussed the previously circulated submission and

SMC report. No declarations of interest were included with the application. 3.2.2 The committee noted the FAF1 submission for the use of tenofovir (Viread®) for

the treatment of chronic hepatitis B in adults with decompensated liver disease. 3.2.3 The committee noted that tenofovir will be used in patients with active chronic

hepatitis B infection (positive HBV DNA) and clinical evidence of decompensated cirrhosis as evidenced by ascites, jaundice, encephalopathy or oesophageal varices.

3.2.4 It was noted that tenofovir would be first-line treatment of HBV in decompensated liver disease as recommended by European Association for the Study of the Liver (EASL) Clinical practice guideline.

3.2.5 It was noted that prescribing will be initiated in secondary care and the treatment of these patients could then be incorporated into the existing Shared Care Protocol (SCP). Patients are expected to recompensate within 6-12 months and will remain on tenofovir long-term.

3.2.6 It was noted that a local Lothian protocol has not been developed. 3.2.7 The evidence is based on a small multi-centre, randomised, double-blind,

controlled phase II study primarily comparing the safety of tenofovir, emtricitabine plus tenofovir, and entecavir. There was no significant difference between the groups for tolerability failure.

3.2.8 The committee agreed to Include tenofovir (Viread®) on the Additional List for the indication in question. The committee members would also support a submission of a SCP.

ACTION: SL/JP

tenofovir disoproxil (as fumarate), 245mg, film-coated tablet (Viread®) No. 720/11 ADVICE: following a full submission: tenofovir disoproxil (as fumarate) (Viread®) is accepted for use within NHS Scotland. Indication under review: Treatment of chronic hepatitis B in adults with decompensated liver disease. Interim results of an ongoing phase II study assessing the safety of tenofovir disoproxil in the treatment of chronic hepatitis B in patients with decompensated liver disease demonstrated that tenofovir was as well tolerated as another nucleoside/nucleotide analogue. Comparative efficacy was not tested in this study, but has been extrapolated from a mixed treatment comparison in treatment-naïve patients with compensated liver disease and hepatitis B eantigen positive infection.



4. SMC latest ‘Not Recommended’ Medicines (November 2012) The committee noted the following medicine not recommended for use by SMC in NHS Scotland:

4.1 racecadotril (Hidrasec Infants®, Hidrasec Children®), Report No. 818/12, is

not recommended for use within NHS Scotland as complementary symptomatic treatment of acute diarrhoea in infants older than three months and in children, together with oral rehydration and the usual support measures, when these measures alone are insufficient to control the clinical condition.

4.2 pazopanib (Votrient®), Report No. 820/12, is not recommended for use within

NHS Scotland for the treatment of adult patients with selective subtype of advanced soft tissue sarcoma (STS) who have received prior chemotherapy for metastatic disease or who have progressed within 12 months after (neo) adjuvant therapy. Efficacy and safety has only been established in certain STS histological tumour subtypes.

4.3 NON-SUBMISSIONS

racecadotril (Hidrasec®), Report No. 832/12, is not recommended for use within NHS Scotland for symptomatic treatment of acute diarrhoea in adults when causal treatment is not possible.

5. Other Medicines Proposed for Use 5.1 moxifloxacin (Avelox®) 5.1.1 The committee noted the FAF3 submission for the use of moxifloxacin (Avelox®)

as part of a tuberculosis treatment regimen if the patient infection is resistant to one or more first line antibacterial agents and is sensitive to moxifloxacin.

5.1.2 No declarations of interests were included with the application. 5.1.3 The committee noted that this is a submission for an off label use of the medicine. 5.1.4 It was noted that the use of moxifloxacin will only be considered if the patients’

infection is resistant to one or more first-line anti-tuberculosis agents, and is sensitive to moxifloxacin and there are no contraindication to the treatment. Decisions will always be based on sensitivity results provided by the TB Reference Laboratory.

5.1.5 Although the trials have used moxifloxacin 5 days per week, international trials have shown superior efficacy with daily rather than intermittent treatment. It was noted that the clinical team has used moxifloxacin daily in the practice with excellent results, and therefore recommend treating patients with daily therapy.

5.1.6 It was noted that a local Lothian protocol has not been developed and that prescribing will take place in hospital by a TB specialist.

5.1.7 The committee noted that there is limited data on safety on long term use. The side effect profile is acceptable and comparable to other anti-tuberculous preparations and superior to alternative second line agents.

5.1.8 The committee agreed to add moxifloxacin (Avelox®) to the Additional List, for Specialist Use only, categorised RED under the ADTC policy for unlicensed and off label medicines. It was noted that the Alert Antibiotic Policy should be updated to include this recommendation.

ACTION: SL/JP



5.2 cabergoline 5.2.1 The committee noted the FAF2 submission for the use of cabergoline (Dostinex®)

as suppression of initiation of lactation in women over 24 weeks with a foetal loss. 5.2.2 No declarations of interests were included with the application. 5.2.3 It was noted that there is no medication currently offered for suppression of

initiation of lactation. 5.2.4 It was noted that a local Lothian protocol has not been developed and that

prescribing will take place in secondary care only. 5.2.5 The evidence is based on a randomised controlled study comparing 1mg dose of

cabergoline with bromocriptine 2.5mg twice a day. There were no significant safety issues recorded.

5.2.6 It was noted that cabergoline should be given with caution to patients with severe cardiovascular disease, Raynaud’s syndrome, renal insufficiency, peptic ulcer or gastrointestinal bleeding, or history of serious, particularly psychotic, mental disorders. Particular care should be taken when patients are taking concomitant psychoactive medication.

5.2.7 The committee agreed to add cabergoline (Dostinex®) to the LJF as a prescribing note, for Specialist Use only.

ACTION: SL/JP 6. SMC Abbreviated Submissions 6.1 lanthanum carbonate (Fosrenol®) 6.1.1 The committee agreed to Include lanthanum carbonate (Fosrenol®) on the

Additional List for the indication in question. ACTION: JP

lanthanum carbonate 750mg and 1000mg oral powder (Fosrenol®) No. 821/12 ADVICE: following an abbreviated submission: lanthanum carbonate oral powder (Fosrenol®) is accepted for restricted use within NHS Scotland. Indication under review: as a phosphate binding agent for use in the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Lanthanum is also indicated in adult patients with chronic kidney disease not on dialysis with serum phosphate levels 1.78 mmol/L in whom a low phosphate diet alone is insufficient to control serum phosphate levels. SMC restriction: as a second-line agent in the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or CAPD where a non-aluminium, non-calcium phosphate binder is required. Lanthanum carbonate is as effective as calcium carbonate in reducing phosphate to target levels.



6.2 bortezomib (Velcade®) 6.2.1 The committee noted that the clinical team are progressing an application for the

indication covered by NICE MTA No 228. 6.2.2 The committee agreed to Include bortezomib (Velcade®) on the Additional List,

for Specialist Use Only, for the indication included in PAS. ACTION: JP

bortezomib (Velcade®) 3.5mg powder for subcutaneous injection No. 822/12 ADVICE: following an abbreviated submission: bortezomib subcutaneous injection (Velcade®) is accepted for use within NHS Scotland. Indications under review: in combination with melphalan and prednisone for the treatment of patients with previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with bone marrow transplant. As monotherapy for the treatment of progressive multiple myeloma in patients who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation. The subcutaneous formulation of bortezomib has been shown to be clinically non-inferior to the intravenous formulation and is the same price. SMC previously accepted bortezomib intravenous injection as monotherapy in the treatment of multiple myeloma when the benefits of a Patient Access Scheme (PAS) were taken into account. The Patient Access Scheme Assessment Group (PASAG) has confirmed that this response-based PAS also applies to the subcutaneous formulation when used in this setting. This SMC advice is therefore contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower. Bortezomib intravenous injection has also been accepted for use in NHS Scotland in specific circumstances in the first line treatment of multiple myeloma as Healthcare Improvement Scotland has endorsed NICE MTA No 228 (Bortezomib and thalidomide for the first line treatment of multiple myeloma) in July 2011. The PAS does not apply to the use of bortezomib in this setting.



6.3 olmesartan / amlodipine / hydrochlorothiazide (Sevikar HCT®) 6.3.1 The committee agreed to Not Include olmesartan/amlodipine/hydrochlorothiazide

(Sevikar HCT®) in the LJF because the medicine does not represent sufficient added benefit to other comparator medicines to treat the condition in question that are already available on the formulary.

ACTION: JP

olmesartan medoxomil / amlodipine besilate / hydrochlorothiazide (Sevikar HCT®) No. 823/12

ADVICE: following an abbreviated submission: olmesartan medoxomil, amlodipine besilate and hydrochlorothiazide (Sevikar HCT®) is accepted for use within NHS Scotland. Indication under review: In adult patients whose blood pressure is not adequately controlled on the combination of olmesartan medoxomil and amlodipine taken as dual-component formulation. Two double-blind randomised studies of triple versus dual therapy demonstrated significantly better outcomes for patients in the triple therapy group in terms of the proportion of patients reaching target blood pressure and reduction in mean systolic and diastolic blood pressure. In patients for whom concomitant use of these medicines is appropriate it allows administration of a single tablet at a lower cost compared to a dual combination product plus single component. Angiotensin receptor blockers are an alternative to angiotensin-converting-enzyme (ACE) inhibitors where these are not tolerated. These fixed dose combinations are among many options for the treatment of hypertension, many of which are less expensive.



6.4 sildenafil (Revatio®) 6.4.1 The committee agreed to Include sildenafil (Revatio®) on the Additional List, for

the indication in question, only if initiated by specialist working in the Scottish Pulmonary Vascular Unit and the Scottish Adult Congenital Cardiac Service.

ACTION: JP 7. Non-submissions to Formulary Committee (October 2012 – 90 day target)

In line with the SGHD/CMO(2012)1 letter that applications should be made to FC within 90 days of SMC issue advice, the committee noted and discussed the following non-submissions:

7.1 nepafenac (Nevanac®), SMC No 813/12 7.1.1 It was noted that a FAF1 is being prepared by the clinical team. 7.1.2 Not included on the LJF, pending protocol.

ACTION: JP 7.2 aclidinium inhalation powder (Eklira Genuair®), SMC No 810/12 7.2.1 It was noted that a FAF1 is being prepared by the clinical team. 7.2.2 Not included on the LJF, pending protocol.

ACTION: JP

7.3 Paper on Formulary Committee process 7.3.1 The committee members noted and discussed the submitted report on process

changes set in line with the SGHD/CMO(2012)1 letter and the achievement of these.

sildenafil (as citrate) 20mg film-coated tablets and 10mg/mL powder for oral solution (Revatio®) No. 809/12 ADVICE: following an abbreviated submission: sildenafil (Revatio®) is accepted for restricted use within NHS Scotland. Indication under review: Treatment of paediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension. Efficacy in terms of improvement of exercise capacity or pulmonary haemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease

SMC restriction: restricted to use on the advice of specialists in the Scottish Pulmonary Vascular Unit and from the Scottish Adult Congenital Cardiac Service.

SMC has previously accepted this orphan indication for oral sildenafil for restricted use within NHS Scotland for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease. Sildenafil is listed in the British National Formulary for Children 2011-2012 for use in pulmonary hypertension after cardiac surgery, weaning from nitric oxide, idiopathic pulmonary arterial hypertension, persistent pulmonary hypertension of the newborn.



7.3.2 It was noted that the committee members were unsure about the reasons driving these timescales but noted that it should not overwrite the safe implementation of these new medicines into clinical practice.

8. Formulary Additions and Amendments 8.1 Formulary Additions ADULT 8.1.1 Wound Section 8.1.1.1 The committee noted and approved the amendments to this section.

ACTION: JP 8.2 Formulary amendment request forms

None.

9. NICE/SIGN/NHS QIS Clinical Guidance November 2012 9.1 TA 266 Cystic Fibrosis – mannitol dry powder for inhalation 9.1.1 The committee noted and discussed the above NICE technology appraisal. 9.2 TA 267 Chronic Heart Failure – ivabradine 9.2.1 The committee noted and discussed the above NICE technology appraisal. 10. Drug Safety Issues – MHRA Advice November 2012 10.1 MHRA Drug Safety Update, Volume 6, Issue 4, November 2012

www.mhra.gov.uk/home/groups/dsu/documents/publication/con207196.pdf 10.1.1 The committee noted the drug safety update. 10.2 Letters for healthcare professionals on the safety of medicines:

pegaptanib (Macugen®) agomelatine (Valdoxan®) pegylated liposomal doxorubicin (Caelyx®) www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/Monthlylistsofinformationforhealthcareprofessionalsonthesafetyofmedicines/CON199563

10.2.1 The committee noted the updated information. 11. Lothian Hypertension Guideline 11.1 The committee discussed and noted the updated Lothian Hypertension Guideline. 11.2 It was agreed to go back to the authors and ask them to add a review date and

provenance to the document. ACTION: JP



12. Antimicrobial Management Team Minutes None.

13. For Information Only 13.1 Formulary Committee Reports and Letters

The committee noted the following Formulary Committee reports and letters: alteplase (Actilyse®) fingolimod (Gilenya®) ivabradine (Procoralan®) velaglucerase (Vpriv®)

14. AOCB None. 15. Date of Next Meeting 15.1 The committee noted that the next meeting would be held on Wednesday 30th

January 2013, at 2pm. (The deadline for submission of papers for this meeting is close of play Tuesday 15th January 2013.)

Joint Area Prescribing and Medicines Optimisation Group Minutes Wednesday 12th December 2012 at 9.30am

OA Room, NHS North Lancashire, Moor Lane Mills, Lancaster

Present: Melanie Preston, (MP) Head of Medicines Management, NHS Blackpool (CHAIR) Julie Lonsdale, (JL) Head of Medicines Management, NHS North Lancashire Louise Winstanley, (LW) Prescribing Support Manager, Fylde & Wyre CCG Kate Anderton, (KtA) Commissioning Manager, Acute, NHS Blackpool Pauline Bourne, (PB) Senior Pharmacist, University Hospital Morecambe Bay Dr Kamlesh Sidhu, (KS) GP Prescribing Lead, Lancashire North CCG

1. Apologies

Dr R Mitchell, Medicines Optimisation Lead, Fylde & Wyre CCG Dr Eric Bonsell, Blackpool CCG Kay Atkinson, Pharmacist, Lancashire North CCG Jackie Moran, Assistant Director of Commissioning, NHS Blackpool Alastair Gibson, Director of Pharmacy, Blackpool Teaching Hospitals Amanda Parkinson, Pharmacist, Lancashire Care Foundation Trust Joanne Ireland, Pharmacist, Lancashire Care Foundation Trust Najam Naeem, Finance Manager (Primary & Community Commissioning) NHS Blackpool

2. Minutes of last meeting Riluzole SCG JL confirmed this has been on the recent agenda of the New Meds Group. JL is to liaise with the LTH Pharmacist and agree the shared care arrangement. Otherwise the minutes were agreed as an accurate account.

3. Declaration of Interest None.

4. Declaration of Confidentiality Resolved: That all the issues discussed at the meeting will be declared as confidential.

5. Action Sheet Update Vitamin D LW advised East Lancs have amended and circulated this document but a final decision has been deferred until 2013. JL had forwarded the UHMB version to Hilary Smith who is collating both documents to adopt as one, which also includes a very useful flow diagram. PB noted there have been some product discrepancies with unlicensed issues. Guidance for Substance Misuse in acute setting. JL has uploaded onto the website but has not circulated any wider.

Shared Care Funding Arrangements This is on the agenda for the December LMMB. JL is reviewing the Traffic Light system and LW is progressing a meeting with Primary Care on how to bring this arrangement forward. Savene Draft Guidance is available and is currently being used. East Lancs and Central Lancs have decided not to prescribe. It is felt that this will also be one of the drugs going to the NCB post April 2013. It is on the agenda for the January LMMB. Ozurdex/Dexamethasone This has been accepted as per NICE guidance although MP noted a patient letter has been received whereby a concern has been raised about access to the service, this query has now been clarified although work is still ongoing to agree the tariff rate. JL advised an FOI has been received in North Lancs highlighting concern with this drug not being commissioned evenly across Lancashire. Action: JL to liaise with Karen Kyle for update. Metolazone MP confirmed BTH have followed the recent UKMI recommendation of using Bendroflumethiazide. Ullipristal MP noted Dr Bonsell raised concern with its efficacy and stated it would have an impact on NHSB prescribing. MP agreed we need to clarify the exact patient numbers as its use is more about patient acceptably. PB confirmed Cumbria are awaiting the SMC decision before deciding. LW suggested to use this to test the new process for the Lancashire-wide group at the February New Meds Group. Agreement should be sought on a Lancashire wide footprint. Action: Bring to New Meds Group and LMMB for discussion. Omacor MP confirmed NHSB are not keen to commission. Fylde & Wyre CCG previously accepted to prescribe for a certain length of time only. LW noted BTH have not yet made a decision and it is still on their pathway. PB stated UHMB have removed it from their pathway. MP commented that Lauren Butler, Cardiac Network has requested feedback from the Cardiologists. Noel Topping, Cardiologist Pharmacist advised they are just awaiting confirmation that we want it removed from the BTH pathway.

LW noted this group agreed at the June JAPAMOG meeting that dietary change should be the priority rather than increase prescribing of Omacor. KS acknowledged there is no indication to prescribe post MI. The GMMC statement has been adopted by East Lancs Action: Agree to confirm with BTH for it to be removed from the current pathway.

6. NICE/New Guidance/Shared Care Guidance NICE Guidance October 2012/November 2012 Denosumab

JL confirmed this was given RED status at the recent New Meds Group. NICE gave a positive TA as an option to prescribe if it is available on a patient access scheme. It was mentioned at the recent UHMB D&T as possibility for Homecare Delivery. PB agreed to contact manufacturer to check if Patient Access Scheme can be extended to Primary Care. To be classed as RED pending any changes. Crohn’s Disease MP gave an overview on the local drug safety monitoring procedure. It was agreed it is a valuable piece work as the management of drug monitoring has become an issue since the required increase in cancer monitoring. She noted the increased use of Miquest for looking at queries on a regular basis. It was also noted that Primus can be used as an information system to check some drug monitoring is adhered to. ESUOM (Evidence Summary: Unlicensed for Off-label Medicine) Relevant to Secondary Care only. Mannitol dry powder JL advised this was given RED status at the recent New Meds Group. It is felt that this will also be one of the drugs going to the NCB post April 2013. Ivabradine An action sheet has been produced and JL is to review to ensure it is in line with recommended NICE Guidance. NICE TA Adherence Worksheets LW noted East Lancs are currently using these available sheets. JL advised in order to raise awareness from 1st April 2013 the new organisations will need to demonstrate adherence to NICE TAs. MP suggested we wait until the national guidance template is available. JL suggested using the TA numbers on the updated RAG list when demonstrating the current NICE guidelines. New Guidance – Rheumatology Pathway MP confirmed following discussion with Dr Rao she confirmed some discrepancies in the comments on the four options outlined in the proposal. Dr Rao advised that Fylde Coast patient numbers are very low (in single figures annually). LW advised no feedback has been received to date from Richard Lee following the meeting two weeks ago. JL noted the presentation by Dr McPhie confirmed that all patients who started on certolizumab have not yet switched back. The London Pilot has since scrapped their scheme as patients were not responding and it was felt that the target numbers may not be reached to ensure the discount is received. In the Preston locality no patients have been switched after three months with approximately £60k being saved on the Scheme. Action: MP to liaise with RL to check if this pathway will be used or whether we await NICE guidance. Request RL bring a paper to LMMB.

7. Horizon Scanning

No items for discussion.

8. Drug applications Lanthanum Powder This has been given AMBER status within Central Lancs and the same consultants who operate as a satellite in UHMB from Preston have requested approval to prescribe. Patient numbers estimated annually are ten. PB noted chewable tablets are available for the same price as the powder, and they are due to come off patent shortly. I Action: Agree to request and given AMBER status. Fluticasone/Formoterol (Flutiform) The East Lancs New Meds Group gave this BLACK status. It does not have a licence for COPD or to use in asthma patients less than twelve years of age. Potential savings could only be achieved at the higher doses for the standard inhaler. LW questioned the introduction of Fluticasone inhalers when they achieve a score of only 4 out of 15. PB noted Cumbria will await the Lothian decision before deciding. Action: Agree to BLACK status. Zostavax The recent LMMB recommended advising against prescribing it within primary care as it is too costly. It was also acknowledged that no national programme has been set up for this vaccine. Action: Agree to BLACK status. Bone metastases from solid tumours – denosumab Previously discussed under NICE guidance.

9. Medicines Management

Dronedarone Following NICE approval in 2010 this was given AMBER status in East Lancs, Cumbria and North Lancs. Following MHRA drug safety advice further restrictions were applied for Consultant use only. Melanie Greenall also produced a safety information sheet for North Lancs. There is now the opportunity to review this decision throughout Lancashire and Cumbria to ensure patients on the UHMB footprint are assigned on the same RAG rating. PB suggested it be brought to the LMMB for a Lancashire wide decision RAG List This item has been deferred from previous meetings. LW noted in section A-B only seven differences were found. LW confirmed a huge amount of decisions have been undertaken by East Lancs but the Fylde Coast has decided not to automatically adopt their options.

She also noted a LMMB tab has been added onto the East Lancs website. Action: MP/JL/LW to meet outside of this meeting in the New Year to discuss options and to finalise before April 2013. POMH UK Audit Programme for 2013/14 MP noted this LCFT audit offers a snapshot of topics they are covering throughout 2013. LW agreed it would be useful to tie in with the work CCGs are also undertaking. Dermatology Specials – Silk Garments KS stated there are an increasing number of requests from Health Visitors, patients and Dermatology consultants for these garments with the costs varying widely. She noted Dermatology Nurses are being swayed and biased by drug representatives in the absence of any evidence for their efficacy. LW confirmed that South Berkshire and Southampton PCTs have both blacklisted the prescribing of these silk garments.

It was agreed the NICE statement is very old and unclear and there are no recent recommended guidelines available. KS has agreed to write to practices as the North Lancs Prescribing Lead to refer prescribing to Secondary Care. JL suggested adding to the New Meds Group agenda to get consensus across Lancashire Action: Agree to amend to BLACK status. LMMB Minutes MP gave a brief overview of these minutes. It was noted that any items requested for prescribing, CCGs would not routinely approve in the absence of any NICE guidance. Horizon Scanning: This has been undertaken by Richard Lee. Fingolimod: LW noted that East Lancs are the only PCT in the locality who have a policy in place for any IFRs received. Action: Bring to next meeting for discussion. Joint Formulary for Psychotropic Medication: JL noted this joint LCFT formulary was discussed at the LMMB. It was agreed to update the PCT websites accordingly. Epanutin Capsules: MP noted pricing would be looked at nationally and referred to the UKMI guidance available. PB stated the Drug Tariff only listed capsules.

10. Minutes of other groups – for information LW suggested for future meetings – the minutes from other groups should be reviewed prior to this meeting to pick out relevant items for discussion.

11. Any other business Tadalafil/vacuum devices for Erectile Dysfunction LW noted the licence is due to change in 2013 but the devices are costing approximately £200 per unit. We will need to review how the commissioning was set up originally. Action: LW to arrange meeting with BTH and put on agenda for next meeting.

Exenatide PB requested this be added to next agenda now that GPs can be asked to prescribe this licenced product following NICE guidance approval. Action: Add to next agenda.

12. Date and time of next meeting

Wednesday 27th February 2013 at 9.30am, NHS North Lancashire, Coniston Room, Wesham

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