effectiveness, tolerability,

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Effectiveness, Tolerability,

and Impact on Quality of Life of the5% Lidocaine Patch

in Diabetic Polyneuropathy

Isnawan Widyayanto

Moderator : dr. Suryadi, SpS



Arch Neurol. 2004;61:914-918

Richard L. Barbano, MD, PhD; David N.

Herrmann, MBBCh; Stephanie Hart-Gouleau,

MD; Janet Pennella-Vaughan, MS, NP; Peter A.Lodewick, MD; Robert H. Dworkin, PhD



Background

• The treatment of painful diabetic polyneuropathy

(DPN) is often inadequate and frequently limited by

the systemic adverse effects of medications,

necessitating the evaluation of novel treatments.

• Potential advantages of the 5% lidocaine patch in

DPN are its lack of systemic adverse effects and

minimal interaction with other medications.



Gabapentin, Pregabalin,

CBZ, Fenitoin, Tramadol,Amitriptilin, Imipramin,

Duloxetine, Venlafaxine,

etc

Letargy, dizziness, nausea,

headache, drowsiness,

constipation, erythema,

Postural hypotension,

bone marrow depression,

SSJ, etc



Neuropathic pain

• Neuropathic pain is a common, often disabling feature

of diabetic polyneuropathy (DPN).

• The treatment of painful DPN is often inadequate and

limited by the systemic adverse effects of currently

available regimens.



Lidocaine

• The efficacy profile of lidocaine as a local anesthetic is

characterized by a rapid onset of action andintermediate duration of efficacy.

• Lidocaine alters signal conduction in neurons by blockingthe fast voltage gated sodium (Na+) channels in the

neuronal cell membrane that are responsible for signalpropagation.

• With sufficient blockage the membrane of thepostsynaptic neuron will not depolarize and will thus fail

to transmit an action potential.• This creates the anaesthetic effect by not preventing pain

signals from propagating to the brain but by stoppingthem before they begin.



Lidocaine (2)

• Topical lidocaine has been shown in some patients to

relieve the pain of postherpetic neuralgia.

• Lidocaine is also the most important antiarrhythmic

drug: it is used intravenously for the treatment of ventricular arrhythmia. However, amiodarone has

been replacing lidocaine as the first-line

pharmacologic management of ventricular

tachycardia.



Relieve pain



Lidocaine (3)

• Systemic exposure to excessive quantities of lidocainemainly result in central nervous system (CNS) andcardiovascular effects.

•

CNS effects may include CNS excitation (nervousness,tingling around the mouth (also known as circumoralparaesthesia), tinnitus, tremor, dizziness, blurredvision, seizures) followed by depression, and withincreasingly heavier exposure: drowsiness, loss of consciousness, respiratory depression and apnoea.

• Cardiovascular effects include hypotension,bradycardia, arrhythmias, and/ or cardiac arrest.



Objective

• To evaluate the effectiveness, tolerability, and

impact on quality of life of the 5% lidocaine

patch in painful diabetic polyneuropathy.



Methods

Design

• Open-label, flexible-dosing, 3-week study with

a 5-week extension.

Setting

• Outpatient clinics and clinical research

centers.



Patients

• 3 participating sites (Rochester, NY; Birmingham, Ala; and

Jacksonville, Fla)

• Volunteer sample of 56 patients with clinically defined painful

diabetic polyneuropathy of longer than 3 months duration.



Inclusion

• An average daily pain diary rating for the

baseline week of at least 4 on the Brief Pain

Inventory (BPI).

• At least 1 hour of moderate or severe pain on

a verbal rating scale.

• A stable analgesic and dosage for at least 1

week before the baseline visit



Exclusion

• Any other pain more severe than the painful DPN.

• Open skin lesions in the area where the patches wereto be applied.

•

Previous treatment with topical lidocaine.• Known hypersensitivity to lidocaine or amide

anesthetics.

• Current treatment with class I antiarrhythmic agents.

• History of excessive alcohol use or illicit drug use.• History of a suicide attempt or a current suicide intent

or plan



Procedure

• Treatment consisted of the immediate dailyapplication to the area of maximal DPN pain of upto 4 lidocaine patches (18 hours on and 6 hours off per day) for 3 weeks.

• Patches could be cut, and the application mannerwas at the subject’s discretion; an attempt wasmade at each dosing period to cover the entirepainful region with lidocaine patches.

• An increase in prior stabilized analgesic therapy orthe introduction of new analgesics was not allowedduring the study period.



What value to compare?

BPI mean dailypain diary rating

SF-MPQ

BPI pain relief score

Baseline 3 weeks

QOLSafety

Tolerability

Primary Secondary

Pain



Primary

BPI mean daily pain

diary rating

SF-MPQ

BPI pain relief score



Brief Pain

Inventory



SF-MPQ

Short Form-

McGill Pain

Questionnaire



Secondary

Sleep Quality

BPI

BDI

POMS



RESULT

56 patients

Alodynia Grup = 19 Non Alodynia Grup = 37

Overall, 70% patients from two groups with week 3 painratings demonstrated a reduction of at least 30% in weeklymean daily pain diary ratings from baseline to week 3.



Pain Measures



Treatment was also accompanied by significant

improvements from baseline to week 3 in the

total sample in sleep quality and all aspects of

pain interference assessed by the BPI.

Significant improvement was also seen in BeckDepression Inventory depression scores and the

Profile of Mood States tension-anxiety,

depression-dejection, anger-hostility, fatigue-inertia, and total mood-disturbance scales in the

total sample.



• In the subgroup of patients who were treated for anadditional 5 weeks, during which taper of concomitant

analgesic therapy was permitted (n = 28), 7 patientsunderwent taper of gabapentin, amitriptylinehydrochloride, or tramadol hydrochloride therapy.

• 3 patients had complete discontinuation of concomitant

pain medication therapy (2 of gabapentin and 1 of amitriptyline).

• 4 patients maintained a reduced dosage,

– 2 receiving gabapentin (50% and 67% reductions),

– 1 receiving tramadol (50% reduction), – 1 receiving amitriptyline (25% reduction).

• No patients required increase in their concomitant painmedication dosages.



Adverse Events

• There were no systemic adverse events reported, andno serious adverse events occurred during the trial.

• 5 patients reported burning sensations at theapplication site, 2 had pain exacerbation, 1 had a

papular rash, and 1 had a photosensitivity reaction.• The mean ± SD plasma lidocaine levels for the cohort

did not differ significantly between the end of treatment weeks 1 (24.1 ± 19.7 ng/mL) and 3 (28.2 ±23.0 ng/mL);

• These levels are well below lidocaine serum levelsassociated with an antiarrhythmic effect (1.5 µg/mL[6.4 µmol/L]) or toxicity (5.0 µg/mL [21.4 µmol/L]).8



Conclusion

• In this open-label trial, the 5% lidocaine patchsignificantly reduced pain and improved QOL inpatients with painful DPN.

• The beneficial response was consistent across all

the measures, occurred in patients whether ornot they had allodynia, and was maintained to 8weeks of treatment.

• After 3 weeks of treatment, two thirds of patients

demonstrated a reduction of at least 30% in theweekly mean daily pain diary ratings, a clinicallyimportant degree of pain relief.



• A secondary objective of the study was to examine

whether treatment with the 5% lidocaine patch

reduced the negative impact of painful DPN onactivities of daily living and psychological distress.

• We found significant improvements in all of the pain

interference measures, 2 measures of depression,

anger-hostility, fatigue-inertia, tension- anxiety, andtotal mood disturbance.

• These results suggest that the generally excellent

tolerability of the 5% lidocaine patch might translateto improvements in QOL that may be less likely to

occur with more poorly tolerated treatments.



• An additional objective was to determine the safety

and tolerability in patients with DPN of 4 lidocainepatches with an application period of 18 hours on

and 6 hours off.

• No significant adverse events were found in the

present study with this regimen, and the resultssuggested that there is no systemic accumulation of

lidocaine during a 3-week treatment period.

• A double blind, randomized control trial must be

conducted to confirm this journal review.



THANK YOU



Antiaritmia



Sistem Keluhan pada Sensorik

Gejala Negatif

Gejala Positif

Baal, geli, seperti pakai sarung tangan, hilang keseimbangan (mata

tertutup ), kurang tangkas, sulit menemukan atau mengenal barang

di dalam kantong / tas, cedera tanpa nyeri , borok.

Rasa terbakar, ditusuk, ditikam, kesetrum, disobek, tegang , diikat,

kulit menjadi sensitif bila terusap. Motorik

Kelumpuhan Distal

Kelumpuhan Proksimal

Gerakan halus tangan terganggu, sulit putar kunci / buka stoples,

jari tertekuk, tersandung, kedua kaki bertabrakan.

Sulit naik tangga, sulit bangkit dari kursi atau lantai, terjatuh sulitbekerja dengan atau mengangkat lengan atas diatas bahu.

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Sudomotor Tidak berkeringat, keringat banyak setempat, berkeringat saat

makan, kulit kering.

effectiveness, tolerability,

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