end-stage copd: huffing and puffing over treatment options · 2020. 10. 19. · end-stage copd:...

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END-STAGE COPD: Huffing and Puffing over

Treatment Options

KRISTIN SPEERPHARM.D., BCPS, cMTM

HOSPICE & PALLIATIVE CARE CLINICAL PHARMACIST

FEBRUARY 12-13, 2019

Cost Effective Medication Management in End Stage COPD

Conflict of Interest and Disclosures of Relevant Financial

Relationships

The planners and presenters (spouse/domestic partner) of this educational activity have disclosed no healthcare related conflicts of interest, commercial interest, or have any related financial relationships/support.

The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.

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Contact Hours –Nursing

1.0 Contact Hour

ProCare Hospice Care is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. (P-0544, 3/31/2021)

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Objectives

1. Select cost-effective treatments for the management ofdyspnea due to COPD in end of life

2. Determine the efficacy and safety of certain oral COPDmedications for end-of-life patients

3. Develop a breathing treatment regimen that negotiatesand resolves the COPD patient’s resistance to “letting go”of inhalers

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Discussion Outline

What basic regimen is cost effective and will work for most patients?

If you want to get technical (and not use basic/empiric regimen)

Cost comparison

Case: COPD new admission

When would the basic regimen not be appropriate?

Case: COPD with tachycardia/tremors

Case: COPD with fluid overload

What else will work well for many patients?

Case: COPD exacerbation, already on basic regimen

What about antibiotics/criteria for use

Continue Daliresp® (roflumilast) or theophylline?

Case: New COPD admission, hesitant about nebs

Proper Inhaler Technique 6


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What Cost-Effective ‘Basic Regimen’ Will Work for Most Patients?

Regardless of current inhaler regimen:

1. Scheduled + PRN nebs (using albuteroland/or ipratropium for most)

2. +/- oral steroids*

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*prednisone, dexamethasone and methylprednisolone are preferred

Putting it together:

1. Scheduled + PRN albuterol/ipratropium

2. +/- prednisone, dexamethasone ormethylprednisolone

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Why would this work for most patients?



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New Regimen Takes Place Of:

Scheduled nebs Long-Acting Inhaler(s) (Controller)

PRN nebs Short-Acting Inhaler(s) (Rescuer)

Oral steroid Inhaled steroid


Nebulizer Overview

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https://my.clevelandclinic.org/health/drugs/4254-home-nebulizer


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Less than half of patients in the general population are able to use their prescribed inhalers adequately1.

What % of hospice patients would you guess are able to use their inhalers adequately?

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If You Want to Get Technical

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If on this: Choose this:Advair Diskus® (fluticasone/salmeterol) Scheduled albuterol +/- oral steroid

Symbicort® (budesonide/formotorol) Scheduled albuterol +/- oral steroid

Perforomist® (aformotorol) Scheduled albuterol

Pulmicort® (budesonide) inhaler or nebs Oral steroid

Trelegy Ellipta® (fluticasone/umeclidinium/vilanterol)

Scheduled albuterol/ipratropium +/- oral steroid

Breo Ellipta® (fluticasone/vilanterol) Scheduled albuterol +/- oral steroid

Combivent Respimat® (albuterol/ipratropium)

Scheduled albuterol/ipratropium

Spiriva HandiHaler® (tiotropium) Scheduled ipratropium

If you prefer not to use DuoNeb® empirically…


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Q: What if I started scheduled DuoNeb®, and the chart says something else?

If no clinical contraindications (most patients don’t have any), the extra component in DuoNeb® that the patient was not getting from their inhaler will likely add benefit without significant side effects.


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Decide in the field using this trick: look at generic names on inhalers

“IUM” = “IUM” (give ipratropIUM neb)

“ROL” = “ROL” (give albuteROL neb; OR albuteROL/ipratroIUM if “IUM” also present)

“ONE” = “ONE” (may give oral steroid)

IpratroIUM neb = Atrovent® nebAlbuteROL neb = Ventolin® neb, Proventil® nebIpratropIUM/AlbuteROL neb – DuoNeb®


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Cost Comparison* - Inhalers:

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Inhaler Retail CostAdvair Diskus ® (fluticasone/salmeterol) $400 (30d)

Symbicort ® (budesonide/formoterol) $330 (30d)

Foradil ® (aformoterol) $300 (30d)

Pulmicort Flexhaler ® (budesonide) $300 (30d)

Trelegy Ellipta ® (fluticasone/umeclidinium/vilanterol) $630 (30d)

Breo Ellipta ® (fluticasone/vilanterol) $420 (30d)

Combivent Respimat ® (albuterol/ipratropium) $450 (30d)

Spiriva HandiHaler ® (tiotropium) $470 (30d)

Ipratropium/albuterol neb + oral steroid $60 for 15 days

*Current approx. retail costs from Goodrx.com. Actual costs to hospice are per pharmacy contracts and will vary.

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High Cost Nebs Retail CostLonhala Magnair® (glycopyrrolate) $1,460 (30d kit)

Pulmicort® (budesonide) $250 (15d)

Brovana® (arformoterol) $600 (15d)

Perforomist® (formoterol) $550 (15d)

Xopenex® (levalbuterol) $350 (15d)

Ipratropium/albuterol neb + oral steroid $60 for 15 days


Cost Comparison* - Nebs:


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Case: COPD New Admission

78 year old female with severe COPD and PMH of CHF and CKD. Receiving Spiriva® (tiotropium), Advair® (fluticasone/salmeterol), and Breo Ellipta® (fluticasone/vilanterol). Completed 5 days prednisone in hospital, and discharged with DuoNeb® (ipratropium/albuterol) PRN orders, which she is hesitant to use. Symptoms remain uncontrolled.

A) Why do you suspect her symptoms remain uncontrolled?

B) Can you identify duplication of therapies?

C) What cost-effective breathing regimen should we switch to?

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A) Why do you suspect her symptoms remain uncontrolled?

Likely poor inhaler technique!

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B) Can you identify duplication of therapies?

Trick: look at generic names – IUM? ROL? ONE?

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C) What cost-effective breathing regimen should we switch to?

Remember: start with “what will work for most patients”; can adapt this regimen

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(Reminder):

1. Scheduled + PRN albuterol/ipratropium

2. +/- prednisone, dexamethasone ormethylprednisolone

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When Would that Basic Regimen NOT Work or be Appropriate?

Adverse reaction (but weigh risk vs benefit!)

Albuterol – possible tachycardia, tremors, anxiety

Oral steroid – possible anxiety/stimulation/insomnia, edema, etc.

Goals of care that preclude nebulizer treatments

Visiting/activities outside of the house/QOL

Goals of care that preclude steroid use

Wound healing

Fluid/edema control (though can still use dexamethasone!)

Glucose control? -does not usually preclude steroid use22


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Case: COPD with Tachycardia/Tremors

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78 year old female with severe COPD and PMH of CHF and CKD. Increased wheezing due to decline. Albuterol/ipratropium (DuoNeb®) scheduled + PRN not well-tolerated due to symptomatic tachycardia and tremors/shakiness. They seem to work when taken, but patient is limiting use due to the adverse reactions.

A) What component of the neb tx is causing tachycardia/tremors?

B) What neb txs can we switch the patient to?

C) Which new neb tx is more cost-effective?



A) What component of the neb tx is likely causing tachycardia/tremors?

Beta agonist! (ROL) - albuterol

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B) What neb txs can we switch the patient to?

A special beta agonist (levalbuteROL neb) (Xopenex® neb)

Anticholinergic only (ipratropIUM neb) (Atrovent® neb)

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C) Which new neb tx is more cost-effective?

A special beta agonist (levalbuteROL neb) (Xopenex® neb): $175/25 nebs*

Anticholinergic only (ipratropIUM neb) (Atrovent® neb): $30/25 nebs*

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Case: COPD with Fluid Overload

78 year old female with severe COPD and PMH of CHF and CKD 4. Increased wheezing due to decline. Nebs scheduled + PRN not fully effective. Clinically significant lower extremity edema and lung congestion. Hx DM2 – taking metformin and glipizide, and not monitoring glucose.

A) Would an oral steroid be appropriate?

B) Does it matter which one?

C) What about diabetes control?

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A) Would an oral steroid be appropriate?

Possible pros: improved breathing control (due to reduced inflammation in thelungs)

Possible cons: increased edema, higher blood glucose, insomnia/anxiety if takentoo late in the day, multiple risks with long-term use

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B) Does it matter which oral steroid?

Dexamethasone: glucocorticoid – no increased edema

Prednisone: mineralocorticoid – increases edema

Methylprednisolone: mineralocorticoid – increases edema

All can increase blood glucose (but usually not a deterrent)

All can increase stimulation/anxiety/insomnia (so take in the morning)

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C) What about glucose control?

Small and/or temporary steroid doses used to help with breathing do not typicallyraise glucose enough to make a clinically significant impact. Can increase DM2meds if needed.

If not monitoring, it is likely not a major problem, or not a goal of care to manageDM2

Glucose ranges up to low-mid 300s typically acceptable on hospice as long as noclinically significant symptoms.2,3 More concerned about hypoglycemia (morereadily symptomatic) rather than hyperglycemia. 30


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What Else Will Work Well for Many Patients?

If already taking nebs scheduled + PRN, + oral steroid (or they are contraindicated)…

Guaifenesin (Robitussin, Mucinex®) or… water!

Saline nebs

Cough suppressants (dextromethorphan,promethazine+codeine, others)

Opioids (morphine, others)

Anxiolytics (lorazepam, others)

Oxygen

Non-pharmacologic therapies 31



Guaifenesin (Robitussin, Mucinex®) or… water!

Use in order to wet, loosen or thin out sticky & tenacious secretions

Need high doses (1200-2400 mg/day) – don’t bother with 100-200mg doses

Water as effective or more effective than guaifenesin – drink up (iftolerated)

Inexpensive

Avoid when patient too weak to expectorate (could worsen symptoms)32


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Saline nebs

Use in order to wet, loosen, or thin out sticky & tenacioussecretions

Use in addition to or instead of guaifenesin/water

Inexpensive

Avoid when patient too weak to expectorate (could worsensymptoms)

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Cough Suppressants

Possible negative: prohibits patient from “getting the gunk out”

Focus usage at night, when coughing interferes with sleep (but ok during theday)

Good for when patient too weak to expectorate (can use with anti-secretory)

Cost effective: dextromethorphan, hydrocodone+homatropine,promethazine+codeine, benzonatate, guaifenesin combo products (+codeine,+dextromethorphan)

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Opioids

Morphine is the gold standard (due to extensive studies), but any mu receptoragonist (aka opioid) will work, including methadone

Reduces oxygen demand and respiratory drive in the brain stem (respiratorycenter) – basically, is “beneficial” respiratory depression

Natural cough suppressant

No clinically significant negative impact on respiratory function in COPD –patients usually benefit4

Cost effective opioids: morphine IR tabs, morphine concentrate, oxycodone IRtabs, methadone (others high cost or costs are rising) 35



Anxiolytics

These DO NOT directly reduce oxygen demand or respiratory drive via thebrain stem like opioids do

Benefits/effects come from cutting the anxiety-dyspnea cycle (reduceanxietyreduce dyspnea)

If no anxiety, probably will not help SOB

Cost-effective and “safer” benzodiazepines: lorazepam, clonazepam

Other cost-effective anxiolytics: trazodone, mirtazapine, buspirone36



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Oxygen

Titrate to 88-92%5

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Non-Pharmacologic

Fans for COPD patients: effective for breathlessness6

Pursed-lip breathing

Cold water to face

Energy conservation

Relaxation techniques

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Case: COPD Exacerbation, on Basic Regimen

78 year old female with severe COPD and PMH of CHF and CKD. Increased wet cough/congestion with increased SOB. New crackles in lung bases heard. No fever, but increased exposure to air pollutants over the past few days. Edema controlled. RR elevated. O2 saturation 92% on 3 L/min. Albuterol/ipratropium scheduled + PRN being used frequently. Dexamethasone therapy was started yesterday. Tolerating therapies well, but needs additional symptom control. On fluid restrictions.

A) What other therapies can we start for increased cough/congestion and SOB?

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Case: COPD Exacerbation, on Basic Regimen

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Guaifenesin (Robitussin®, Mucinex®) or… water! YES! High doseMucinex® tabs ok (avoid liquid since fluid-restricted)

Saline nebs –eh, already using a lot of nebs

Cough suppressants –can use, but avoid when greater goal is toexpectorate

Opioids (morphine, others) YES! Select based on pt-specific factors

Anxiolytics (lorazepam, others) –only if anxiety is contributing to SOB

Oxygen –not hypoxemic, can keep current rate

Pursed lip, fan/airflow, cold water, relaxation YES!

Remember: If already taking nebs scheduled + PRN, + oral steroid (or they are contraindicated)…


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What About Antibiotics (Abx)?

For Acute Respiratory Symptoms (COPD Exacerbation):

First, consider viral infection!

COPD exacerbations are mainly triggered by viral infections5

Abx will not work

Second, consider environmental triggers

Common

Air pollution, allergens, temperature changes

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For Acute Respiratory Symptoms (COPD Exacerbation):

For hospice: might try IF patient meets certain criteria (see nextslide)

Use of abx remains controversial5

Abx selection based on many factors and not part of this presentationscope

not always azithromycin!

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Criteria for Antibiotic Use in Acute COPD Exacerbation5

When there is increased sputum purulence AND 1+ other CardinalSymptom

Other Cardinal Symptoms: increased dyspnea, increased sputumvolume

(Require mechanical ventilation – not generally applicable tohospice)

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For Chronic Respiratory Symptoms (Prevention of COPD Exacerbations):

For hospice: benefit does not seem to outweigh potential risks

Data for azithromycin only (do not use other abx for prevention):7

Only 0.35 fewer exacerbations over 12 months vs placebo (1.48 vs 1.83exacerbations per person per year)7

Dyspnea scores improved by 2 pts vs placebo (4 points considered‘clinically significant’)7

Risks: abx resistance,7,8 hearing loss (sometimes permanent),arrhythmias7

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2+ COPD exacerbations in the previous year [most hospice COPD pts]

QTc < 450 msec on ECG, and not taking other QTc-prolonging drugs(n/a on hospice)

No cardiovascular disease (heart failure, coronary artery disease,peripheral vascular disease, or cerebrovascular disease) [good luck!]

No hearing loss on formal audiology testing (n/a on hospice)

A sputum culture negative for mycobacteria (n/a on hospice)

Heart rate < 100 / min

ALT and AST < 3 times normal (n/a on hospice)45

Criteria for Antibiotic Use in Prevention of COPD Exacerbations7,9

Continue Roflumilast (Daliresp®)?

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NO!


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Continue Roflumilast (Daliresp®)?

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“But why not just keep them on it, if they insist, even if itmay not prevent any exacerbations/hospitalizations whileon hospice?”

Retail cost (Goodrx.com): approx. $210/15 days

Potential adverse effects11 – weight loss, diarrhea, nausea,headache

Drug Interactions (mainly via CYP3A4 – lots of medications)11

An extra pill to take

Continue Theophylline?

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No – discontinue (consider taper off) maintenancetherapy

Do not add for exacerbations5

Increased adverse effects and risks of toxicity (dose-dependent) Palpitations/arrhythmias (can be fatal), seizures, headache,

insomnia, nausea, heartburn

Narrow therapeutic & toxic serum level thresholds (easilybecomes toxic, or even non-therapeutic)

Benefit occurs only when near-toxic doses are given5

Many drug interactions (warfarin, digoxin, etc)


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Case: COPD New Admission, Hesitant about Nebs

“But I don’t WANT to stop these inhalers, they’re my lungs!”

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Case: COPD New Admission, Hesitant about Nebs

“But I don’t WANT to stop these inhalers, they’re my lungs!”

Try alternating inhaler and neb therapies by slowly reducing #puffs and/orfrequency of inhaler doses, while slowly increasing frequency of nebtreatments over time

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Example: Spiriva® every other day and Symbicort® once daily, and DuoNeb® once or twice daily, working up to goal DuoNeb® scheduled TID-QID frequency (add oral steroid if needed)

Follow Up Question: Why don’t we really need to worry aboutpatient getting duplicate or over-exposure of inhaled therapies?


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Proper Inhaler Technique – Overview12

There are so many inhalers – each with own directions

Generics may not operate the same way as Brands

Look up specific usage/cleaning/storage directions foreach inhaler

Use teach-back method to ensure patient can adequatelyuse

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Proper Inhaler Technique – Education Points13

Questions Patients Should Ask: Do I need to shake my inhaler before using it?

Do I need to "prime" my inhaler with test sprays? If so, how andwhen?

Should I clean my inhaler? If so, with what (e.g., dry cloth, dampcloth, running water)?

Use bronchodilators first (relax and open airways foradditional medication) “ROL” medications – albuterol, salmeterol, etc. Often found

in combination with anticholinergic and/or steroid

Rinse mouth with water and spit out after steroid inhaler

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Proper Inhaler Technique – Education Points13

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Metered-dose Inhalers (MDI):

Dry-powder Inhalers (DPI):

Soft-mist Inhalers:

Shake most before use Do not shake Do not shake

Prime most before first use No need to prime Prime before first use

Slow deep breath Quick deep breath Slow deep breath

General Usage Techniques (does not apply to every/all inhaler in each category):

Summary (satisfying the objectives)

1. Most patients will respond well to scheduled + PRNalbuterol/ipratropium nebs +/- prednisone or dexamethasone. Otherdrug and non-drug therapies can be added depending on symptom typeand based on patient-specific factors.

2. Oral therapies approved for use in COPD are not always safe oreffective in end-stage patients on hospice. Use abx judiciously; dalirespis usually unnecessary; avoid theophylline.

3. Alternating and increasing neb treatments, while slowly reducinginhaler use can help patients wean off expensive and difficult to useinhalers. Ensure proper inhaler technique if patients continue theirinhalers.

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Thank you!

Questions/Discussion

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References1. Barrons R, Pegram A, Borries A. Inhaler device selection: special considerations in

elderly patients with chronic obstructive pulmonary disease. Am J Health Syst Pharm2011;68:1221-32.

2. King EJ, Haboubi H, Evans D, et al. The management of diabetes in terminal illnessrelated to cancer. QJM. 2012; 105:3-9.

3. McCoubrie R, Jeffrey D, Paton C, Dawes L. Managing diabetes mellitus in patientswith advanced cancer: a case note audit and guidelines. Eur J Cancer Care. 2005;14(3):244-8.

4. Jennings AL, Davies AN, Higgins JP, et al. A systematic review of the use of opioids inthe management of dyspnoea. (review) Thorax 2002;57(11):939-44

5. Global Strategy for Diagnosis, Management and Prevention of COPD, Global Initiativefor Chronic Obstructive Lung Disease (GOLD) 2018. http://www.goldcopd.org.

6. Galbraith, Sarah et al. Does the Use of a Handheld Fan Improve Chronic Dyspnea? ARandomized, Controlled, Crossover Trial. Journal of Pain and Symptom Management.2010;39(5):831 – 838. DOI: https://doi.org/10.1016/j.jpainsymman.2009.09.024

7. Albert RK, et al. for the COPD Clinical Research Network. Azithromycin forPrevention of Exacerbations of COPD. N Engl J Med 2011; 365:689-698. DOI:10.1056/NEJMoa1104623

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References

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8. Himanshu Desai, Sandra Richter, Gary Doern, et al. Antibiotic Resistance in Sputum Isolatesof Streptococcus pneumoniae in Chronic Obstructive Pulmonary Disease is Related toAntibiotic Exposure, COPD. Journal of Chronic Obstructive Pulmonary Disease. 2010;7(5): 337-344. DOI: 10.3109/15412555.2010.510162

9. PulmCC Inc. Antibiotics (azithromycin) to prevent COPD exacerbations (Review). OnlineArticle. 2013. URL: https://pulmccm.org/review-articles/antibiotics-azithromycin-to-prevent-copd-exacerbations-review-nejm/

10. Daliresp Efficacy. Daliresphcp.com. URL: https://www.daliresphcp.com/daliresp-efficacy.html.html. Accessed 2/3/2019.

11. Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2019; February 3, 2019.

12. Clinical Resource, Correct Use of Inhalers. Pharmacist’s Letter/Prescriber’s Letter. January2017.

13. Tips for Correct Use of Inhalers. Pharmacist’s Letter. 2016; Detail-Document#: 330106.https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2017/Jan/Tips-for-Correct-Use-of-Inhalers-10563


end-stage copd: huffing and puffing over treatment options · 2020. 10. 19. · end-stage copd:...

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