Comparison of five commonly-available, lidocaine-containing topical anesthetics and their effect on serum levels of lidocaine and its metabolite monoethylglycinexylidide (MEGX)

Background: Topical anesthetics are commonly applied for a variety of indications. Several lidocaine-containing topical anesthetics are available for purchase over the counter (OTC). Recently, the authors' group has shown that there is great interindividual discrepancy in the manner in which lidocaine is absorbed and metabolized for even a single OTC product.Objectives: The authors compare five commonly-available lidocaine preparations and their levels of absorption when applied to the face. Three of the preparations are available OTC; two require prescriptions and were compounded in a pharmacy.Methods: Twenty-five subjects enrolled in this Institutional Review Board-approved study were randomly assigned to one of five groups. The five topical anesthetics were LMX-4 (4% lidocaine; Biopelle/Ferndale Laboratories, Ferndale, Michigan), Topicaine (4% lidocaine; Ebsa Laboratories, Jupiter, Florida), 2.5% lidocaine/2.5% prilocaine (generic EMLA preparation; High Tech Pharmaceuticals, Amityville, New York), LET (4% lidocaine, 1:2000 epinephrine, and 0.5% tetracaine), and BLT (20% benzoncaine, 6% lidocaine, and 4% tetracaine). After a patch test for adverse reactions, the topical anesthetic was applied to each patient's face and neck and covered with an occlusive dressing for 60 minutes. Blood was drawn at 90, 120, 150, 240, and 480 minutes to measure serum levels of lidocaine and monoethylglycinexylidide (MEGX).Results: The average age of the 17 women and eight men included in the study was 26 years (range, 22-62 years), and the average weight was 70.9 kg (range, 46.4-96.4 kg). The OTC preparations had the highest serum lidocaine and MEGX levels. Topicaine had the greatest serum levels of individual lidocaine absorption (0.808 μg/mL), followed by generic EMLA (0.72 μg/mL), LMX-4 (0.44 μg/mL), BLT (0.17 μg/mL), and LET (0.13 μg/mL). On average, Topicaine had the highest serum lidocaine and MEGX levels: 0.438 μg/mL and 0.0678 μg/mL, respectively. There were significant interindividual differences between the serum levels of MEGX and lidocaine in all groups except LET (P <.0001). There were significant differences between the 4% lidocaine-containing preparations (P =.0439); the 2.5% preparation had a greater absorption than the 4% lidocaine-containing preparation and the 6% lidocaine preparation (P =.0016). There were three adverse reactions in patients who received OTC preparations, one of which resulted in postinflammatory hyperpigmentation.Conclusions: This study demonstrates that although topical anesthetics are considered safe, some individuals have unpredictably high absorption levels. This study also demonstrates that the concentration of lidocaine, the formulation of the drug, and the individual patient all have significant effects on serum levels of lidocaine. The authors recommend that even OTC topical anesthetics be used under the supervision of a healthcare professional to avoid adverse toxic effects and, in rare cases, death.Level of Evidence: 2