24‐HOUR APPLICATION OF THE LIDOCAINE PATCH 5% FOR 3 CONSECUTIVE DAYS IS SAFE AND WELL TOLERATED IN HEALTHY ADULT MEN AND WOMEN

Arnold R. Gammaitoni, PharmD, Endo Pharmaceuticals, Chadds Ford, PA; Nancy A. Alvarez, PharmD, Endo Pharmaceuticals, Chadds Ford, PA Objective: To determine the tolerability and evaluate the pharmacokinetics and safety of continuous 24‐hour application of the lidocaine patch 5% (Lidoderm®), a site‐specific general analgesic that relieves pain by reducing peripheral nociceptive impulse generation. Background: The lidocaine patch 5% currently has an FDA‐approved indication for the treatment of postherpetic neuralgia (maximum dose: 3 patches for 12 h/d). A recent study reported no significant safety findings, laboratory abnormalities, or adverse effects of 4 lidocaine patches applied for an 18‐hour period on 3 consecutive days. The present study was designed to determine the safety and tolerability of 4 patches applied for 24 hours either once daily or every 12 hours on 3 consecutive days. Methods: In this open‐label study, 20 healthy subjects were randomized to apply 4 patches either QD or BID to the upper back for 3 consecutive days. Plasma drug levels, local anesthetic effect, and occurrence of adverse effects were evaluated. Results: The maximal plasma lidocaine concentrations were 212.3 and 231.0 ng/mL for the QD and BID regimens, respectively, representing approximately 1/6 the level required for cardiac activity (1500 ng/mL) and 1/20 that for toxicity (5000 ng/mL). Adjusted area under the curve values were 4099.8 and 4703.5 ng·h/mL and half‐life values were 6.8 and 7.9 hours with QD and BID use, respectively. Sensory examination (light touch and pin prick) revealed no loss or alteration of sensation at the application site in any subject. Erythema, which occurred in 14 subjects and was very slight (n = 12) to moderate (n = 2), did not result in any discontinuations. There were no reports of edema at any application sites throughout the study. No reports of systemic adverse events related to study medication were noted. Conclusions: Continuous 24‐hour application of 4 lidocaine patches produced plasma lidocaine levels well below those associated with cardiac activity/toxicity. There was no reported alteration in sensation at any application site, demonstrating that continuous 24‐hour application of the lidocaine patch 5% still did not produce a local anesthetic effect in the skin underlying patch application. Both dosing regimens (4 patches QD and BID) were well tolerated and no systemic adverse events related to the study medication were reported.