Drugs

, Volume 69, Issue 15, pp 2149–2165 | Cite as

Lidocaine 5% Medicated Plaster

A Review of its Use in Postherpetic Neuralgia
Adis Drug Evaluation

Summary

Abstract

The lidocaine 5% medicated plaster (Versatis®) is a topical analgesic, indicated for the symptomatic relief of neuropathic pain associated with previous herpes zoster infection (i.e. postherpetic neuralgia [PHN]) in adults.

The lidocaine 5% medicated plaster has a direct local action with low systemic exposure and is effective in the treatment of patients with PHN. Limited data, from a study in patients with PHN or painful diabetic neuropathy, show that short-term treatment with lidocaine 5% medicated plaster was associated with numerically higher pain intensity response rates than pregabalin in the PHN subgroup. The efficacy of the lidocaine 5% medicated plaster was maintained in the longer term. Additionally, the lidocaine 5% medicated plaster was well tolerated, with application site reactions being the most commonly reported drug-related adverse events; drug-related adverse events were few, and most were of mild to moderate severity. Due to its low systemic exposure, the drug may be of particular advantage in the treatment of patients with a low tolerance for adverse events, or who are receiving concomitant drugs that may otherwise result in drug interactions. Thus, the lidocaine 5% medicated plaster is a useful first-line option for the treatment of patients with PHN.

Pharmacological Properties

The lidocaine 5% medicated plaster is a 10 cm by 14 cm adhesive plaster, containing 700 mg (5% w/w) lidocaine. Lidocaine is a voltage-gated sodium channel antagonist, widely believed to exert its analgesic effects by preventing the generation and conduction of neuronal action potentials by binding to the sodium channels on hyperactive or damaged nociceptors, where they are present in abnormally high numbers. The lidocaine 5% medicated plaster has a direct local action providing pain relief without an anaesthetic effect causing numbness. The plaster also acts as a barrier to stimuli triggering pain sensation; this contributes to its analgesic efficacy.

Lidocaine was slowly absorbed on application of the lidocaine 5% medicated plaster, with a time to maximum plasma concentration (Cmax) of 14 hours in PHN patients. Cmax (0.052 mg/L) was well below antiarrhythmic therapeutic concentrations (2–5 mg/L) and toxic concentrations (>6 mg/L). Lidocaine did not accumulate, and steady-state concentration was reached within 4 days. The systemic exposure to lidocaine was low at 3%, and increased less than proportionally to the number of plasters used. Lidocaine had a volume of distribution of 1.3L/kg.

Volume of distribution is increased in patients with hepatic disease and decreased in patients with congestive heart failure. Patients with cardiac, renal or hepatic insufficiency may show delayed excretion of lidocaine and its metabolites.

Therapeutic Efficacy

In two randomized, double-blind, placebo-controlled studies (in which patients received lidocaine 5% medicated plaster for ≥1 month before randomization), an advantage for lidocaine 5% medicated plaster over placebo in patients with PHN was generally seen after ≤2 weeks’ treatment, with regard to time to exit from treatment period because of lack of efficacy (primary endpoint). The difference between groups was statistically significant in one study but not in the other study in the primary population.

In a randomized, open-label, 4-week study comparing lidocaine 5% medicated plaster and pregabalin in patients with PHN or painful diabetic polyneuropathy, the primary endpoint of Numerical Rating Scale-3 response rate (response defined as a reduction of ≥2 points or an absolute value of ≤4) was numerically higher with lidocaine 5% medicated plaster than with pregabalin in the subgroup of patients with PHN (statistical analysis not performed). Lidocaine 5% medicated plaster also appeared to be beneficial to patient health-related quality of life on the EuroQol-5 dimension quality of life index.

Lidocaine 5% medicated plaster was effective in the long-term (1-year) treatment of neuropathic pain symptoms in newly recruited patients with PHN and those previously treated with lidocaine 5% medicated plaster. Efficacy was generally seen to continue throughout an additional 1- to 2-year extension period.

Tolerability

The lidocaine 5% medicated plaster was well tolerated in patients with PHN, with most adverse events being of mild to moderate severity. In clinical trials, the most common drug-related adverse event in lidocaine 5% medicated plaster recipients was application site reactions. The lidocaine 5% medicated plaster had similar tolerability to placebo and was better tolerated than pregabalin, with significantly fewer drug-related adverse events occurring in lidocaine 5% medicated plaster recipients than in pregabalin recipients. Lidocaine 5% medicated plaster appeared to be related to fewer serious adverse events than pregabalin, and drug-related adverse events led to fewer lidocaine 5% medicated plaster than pregabalin recipients withdrawing from the study. The lidocaine 5% medicated plaster also appeared to be well tolerated in the longer term.

Pharmacoeconomic Considerations

Lidocaine 5% medicated plaster was predicted to be cost effective relative to gabapentin and pregabalin in patients with PHN who had experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants, according to the results of three pharmacoeconomic analyses using Markov modelling and conducted from the perspective of the healthcare payer. The incremental cost per quality-adjusted life-year gained with lidocaine 5% medicated plaster versus gabapentin or pregabalin was below commonly accepted cost-effectiveness thresholds. The drug was also predicted to be cost effective relative to gabapentin and pregabalin with regard to the cost per additional month without symptoms or intolerable adverse effects.

References

  1. 1.
    Johnson RW, Wasner G, Saddier P, et al. Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging 2008; 25(12): 991–1006PubMedCrossRefGoogle Scholar
  2. 2.
    Volpi A, Gross G, Hercogova J, et al. Current management of herpes zoster: the European view. Am J Clin Dermatol 2005; 6(5): 317–25PubMedCrossRefGoogle Scholar
  3. 3.
    Douglas MW, Johnson RW, Cunningham AL. Tolerability of treatments for postherpetic neuralgia. Drug Saf 2004; 27(15): 1217–33PubMedCrossRefGoogle Scholar
  4. 4.
    Campbell BJ, Rowbotham M, Davies PS, et al. Systemic absorption of topical lidocaine in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster. J Pharm Sci 2002 May; 91(5): 1343–50PubMedCrossRefGoogle Scholar
  5. 5.
    Grunenthal Ltd. Versatis (lidocaine) 5% medicated plaster: summary of product characteristics (UK) [online]. Available from URL: http://emc.medicines.org.uk/medicine/19291 [Accessed 2009 Apr 28]
  6. 6.
    Davies PS, Galer BS. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs 2004; 64(9): 937–47PubMedCrossRefGoogle Scholar
  7. 7.
    Cummins TR. Setting up for the block: the mechanism underlying lidocaine’s use-dependent inhibition of sodium channels. J Physiol 2007 Jul 1; 582 Pt 1: 11CrossRefGoogle Scholar
  8. 8.
    Gammaitoni AR, Alvarez NA, Galer BS. Pharmacokinetics and safety of continuously applied lidocaine patches 5%. Am J Health Syst Pharm 2002 Nov 15; 59(22): 2215–20PubMedGoogle Scholar
  9. 9.
    Chabal C, Russell LC, Burchiel KJ. The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 1989 Sep; 38(3): 333–8PubMedCrossRefGoogle Scholar
  10. 10.
    Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992 Feb; 48(2): 261–8PubMedCrossRefGoogle Scholar
  11. 11.
    Woolf CJ, Wiesenfeld-Hallin Z. The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord. Pain 1985 Dec; 23(4): 361–74PubMedCrossRefGoogle Scholar
  12. 12.
    Baron R, Mayoral V, Leijon G, et al. 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study. Curr Med Res Opin 2009 Jul; 25(7): 1663–76PubMedCrossRefGoogle Scholar
  13. 13.
    Binder A, Bruxelle J, Rogers P, et al. Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial. Clin Drug Investig 2009; 29(6): 393–408PubMedCrossRefGoogle Scholar
  14. 14.
    Wasner G, Kleinert A, Binder A, et al. Postherpetic neuralgia: topical lidocaine is effective in nociceptor-deprived skin. J Neurol 2005 Jun; 252(6): 677–86PubMedCrossRefGoogle Scholar
  15. 15.
    Meier T, Wasner G, Faust M, et al. Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study. Pain 2003 Nov; 106(1-2): 151–8PubMedCrossRefGoogle Scholar
  16. 16.
    Geha PY, Baliki MN, Chialvo DR, et al. Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain 2007 Mar; 128(1-2): 88–100PubMedCrossRefGoogle Scholar
  17. 17.
    Rowbotham MC, Davies PS, Verkempinck C, et al. Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 1996 Apr; 65(1): 39–44PubMedCrossRefGoogle Scholar
  18. 18.
    Galer BS, Rowbotham MC, Perander J, et al. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain 1999 Apr; 80(3): 533–8PubMedCrossRefGoogle Scholar
  19. 19.
    Hans G, Sabatowski R, Binder A, et al. Efficacy and tolerability of a 5% lidocaine medicated plaster for the topical treatment of post-herpetic neuralgia: results of a long-term study. Curr Med Res Opin 2009 Apr; 25(5): 1295–305PubMedCrossRefGoogle Scholar
  20. 20.
    Liedgens H, Hertel N, Gabriel A, et al. Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a German perspective. Clin Drug Investig 2008; 28(9): 583–601PubMedCrossRefGoogle Scholar
  21. 21.
    Dakin H, Nuijten M, Liedgens H, et al. Cost-effectiveness of a lidocaine 5% medicated plaster relative to gabapentin for postherpetic neuralgia in the United Kingdom. Clin Ther 2007 Jul; 29(7): 1491–507PubMedCrossRefGoogle Scholar
  22. 22.
    Dakin HA, Nuijten MJC, Liedgens H, et al. Cost-utility analysis evaluating lidocaine 5% medicated plaster relative to gabapentin for post-herpetic neuralgia in Scotland. Value Health 2007 May 30; 10(3): A9–10CrossRefGoogle Scholar
  23. 23.
    Endo Pharmaceuticals. Lidoderm (Lidocaine patch 5%): US prescribing information [online]. Available from URL: http://www.endo.com/PDF/lidoderm_pack_insert.pdf [Accessed 2009 Jul 21]
  24. 24.
    European Medicines Agency. Zostavax (varicella-zoster virus vaccine): summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/zostavax/emea-combined-h674en.pdf [Accessed 2009 Jul 22]
  25. 25.
    Dworkin RH. Post-herpetic neuralgia. Herpes 2006 Jun; 13 Suppl. 1: 21–7AGoogle Scholar
  26. 26.
    Finnerup NB, Otto M, Jensen TS, et al. An evidence-based algorithm for the treatment of neuropathic pain. MedGenMed 2007; 9(2): 36PubMedGoogle Scholar
  27. 27.
    Attal N, Cruccu G, Haanpaa M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 2006 Nov; 13(11): 1153–69PubMedCrossRefGoogle Scholar
  28. 28.
    Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007 Dec 5; 132(3): 237–51PubMedCrossRefGoogle Scholar
  29. 29.
    Christo PJ, Hobelmann G, Maine DN. Post-herpetic neuralgia in older adults: evidence-based approaches to clinical management. Drugs Aging 2007; 24(1): 1–19PubMedCrossRefGoogle Scholar
  30. 30.
    Baranowski AP, De Courcey J, Bonello E. A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia. J Pain Symptom Manage 1999 Jun; 17(6): 429–33PubMedCrossRefGoogle Scholar
  31. 31.
    Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991 Jul; 41(7): 1024–8PubMedCrossRefGoogle Scholar
  32. 32.
    Priano L, Gasco MR, Mauro A. Transdermal treatment options for neurological disorders: impact on the elderly. Drugs Aging 2006; 23(5): 357–75PubMedCrossRefGoogle Scholar
  33. 33.
    Delorme C, Navez M, Legout V, et al. Lidocaine patch: 5 years of clinical experience [abstract no. PW 349]. 12th World Congress on Pain; 2008 Aug 17–22; GlasgowGoogle Scholar
  34. 34.
    Galer BS, Gammaitoni AR. More than 7 years of consistent neuropathic pain relief in geriatric patients. Arch Intern Med 2003 Mar 10; 163(5): 628PubMedCrossRefGoogle Scholar
  35. 35.
    Baron R, Mayoral V, Leijon G, et al. Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin 2009 Jul; 25(7): 1677–87PubMedCrossRefGoogle Scholar
  36. 36.
    Gammaitoni A, Oleka N, Galer B. Lidocaine 5% patch improves outcomes for post-herpetic neuralgia patients receiving COX-2/anti-inflammatory, opioid, or adjuvant analgesics [abstract no. 766]. J Pain 2005 Mar; 6 (3 Suppl. 1): S49CrossRefGoogle Scholar
  37. 37.
    Gammaitoni AR, Davis MW. Pharmacokinetics and tolerability of lidocaine patch 5% with extended dosing. Ann Pharmacother 2002 Feb; 36(2): 236–40PubMedCrossRefGoogle Scholar
  38. 38.
    Attal N, Brasseur L, Chauvin M, et al. Effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA®) cream on spontaneous and evoked pain in post-herpetic neuralgia. Pain 1999 May; 81(1-2): 203–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore 0754, AucklandNew Zealand

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