Lidocaine 5% Medicated Plaster

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.

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 (C_max) of 14 hours in PHN patients. C_max (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.

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.

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.