Mechanism of Action: Lidocaine is an amide-type local anesthetic agent and tetracaine is an ester-type local anesthetic agent. Both lidocaine and tetracaine block sodium ion channels required for the initiation and conduction of neuronal impulses which, in certain instances, results in local anesthesia. When applied to intact skin, Pliaglis (lidocaine and tetracaine) provides local dermal analgesia by the release of lidocaine and tetracaine from the peel into the skin.
Duration of analgesia was evaluated using a pinprick test in 40 adult volunteers. The median duration of analgesia was 11 hours. There was no difference between the 30-minute and 60-minute Pliaglis (lidocaine and tetracaine) application periods with respect to the mean for time to return of sensation. However, 55% of Pliaglis (lidocaine and tetracaine) treated subjects still reported diminished sensation at the end of the 13-hour study period.
Absorption: The amount of lidocaine and tetracaine systemically absorbed from Pliaglis (lidocaine and tetracaine) is directly related to both the duration of application and the surface area over which it is applied, Table 1. Application of 59 g of Pliaglis (lidocaine and tetracaine) over 400 cm² for up to 120 minutes to adults produces peak plasma concentrations of lidocaine of 220 ng/mL. Tetracaine plasma levels were not measurable ( < 0.9 ng/mL). Systemic exposure to lidocaine, as measured by Cmax and AUC0-24, was proportional to the application area, and increased with application time up to 60 minutes.
Table 1. Absorption of lidocaine and tetracaine following
application of Pliaglis (lidocaine and tetracaine)
|21||400||18 - 64||4||30||Lidocaine, 1.5||49||4.0|
|Tetracaine, 1.5||< 0.9||na|
|33||400||18 - 64||4||60||Lidocaine, 2.3||96||2.8|
|Tetracaine, 2.3||< 0.9||na|
|31||400||≥ 65||6||60||Lidocaine, 2.2||48||3.8|
|Tetracaine, 2.2||< 0.9||na|
|na = not applicable|
Distribution: When lidocaine is administered intravenously to healthy volunteers, the steady-state volume of distribution is approximately 0.8 to 1.3 L/kg. At lidocaine concentrations observed following the recommended product application, approximately 75% of lidocaine is bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 mg/mL of free base) the plasma protein binding of lidocaine is concentration dependent. Lidocaine crosses the placental and blood brain barriers, presumably by passive diffusion. CNS toxicity may typically be observed around 5000 ng/mL of lidocaine; however, a small number of patients reportedly may show signs of toxicity at approximately 1000 ng/mL.
Volume of distribution and protein binding have not been determined for tetracaine due to rapid hydrolysis in plasma.
Metabolism: It is not known if lidocaine or tetracaine is metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. The major metabolic pathway of lidocaine, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4. The metabolite, 2,6-xylidine, has unknown pharmacologic activity. Following intravenous administration of lidocaine, MEGX and GX concentrations in serum range from 11% to 36% and from 5% to 11% of lidocaine concentrations, respectively. Serum concentrations of MEGX were about one-third the serum lidocaine concentrations.
Tetracaine undergoes rapid hydrolysis by plasma esterases. Primary metabolites of tetracaine include para-aminobenzoic acid and diethylaminoethanol, both of which have an unspecified activity.
Elimination: The half-life of lidocaine elimination from the plasma following intravenous administration is approximately 1.8 hr. Lidocaine and its metabolites are excreted by the kidneys. More than 98% of an absorbed dose of lidocaine can be recovered in the urine as metabolites or parent drug. Less than 10% of lidocaine is excreted unchanged in adults, and approximately 20% is excreted unchanged in neonates. The systemic clearance is approximately 8–10 mL/min/kg. During intravenous studies, the elimination half-life of lidocaine was statistically significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours).
The half-life and clearance for tetracaine has not been established for humans, but hydrolysis in the plasma is rapid.
Elderly: After application of 31g of Pliaglis (lidocaine and tetracaine) over 400 cm² for 60 minutes, mean peak plasma levels of lidocaine were 48 ng/mL for elderly patients ( > 65 years of age, mean 68.0 ±3.2 years, n = 6). These levels are similar to or lower than those for younger patients receiving similar amounts of Pliaglis (lidocaine and tetracaine) .
Cardiac, Renal and Hepatic Impairment: No specific pharmacokinetic studies were conducted. The half-life of lidocaine may be increased in patients with cardiac or hepatic dysfunction. There is no established half-life for tetracaine due to rapid hydrolysis in the plasma.
In four clinical trials, adult patients were treated with Pliaglis (lidocaine and tetracaine) and/or placebo prior to undergoing a superficial dermatologic procedure. Drug was applied for 20 or 30 minutes for dermatologic procedures such as dermal filler injection, pulsed dye laser therapy, and facial laser resurfacing. Drug was applied for 60 minutes for laser-assisted tattoo removal. Treatment with Pliaglis (lidocaine and tetracaine) resulted in statistically significantly less pain compared to placebo treatment, as measured by a 100 mm visual analog scale (VAS). Patient efficacy ratings are shown in Table 2.
Table 2. Summary of patient evaluations following application
of Pliaglis (lidocaine and tetracaine) and placebo
|Dermatologic Procedure||Mean VAS score|
|20 Min Application|
|Pulsed Dye Laser Therapy (N=80)||16||31|
|30 Min Application|
|Non-Ablative Laser Facial Resurfacing (N=54)||21||38|
|Dermal Filler Injections (N=70)||24||37|
|60 Min Application|
|Laser-Assisted Tattoo Removal (N=62)||39||59|
In a trial of Pliaglis (lidocaine and tetracaine) in pediatric patients aged 5-17 years undergoing venipuncture (blood draw or intravenous line placement), Pliaglis (lidocaine and tetracaine) applied for 30 minutes failed to show efficacy over placebo in reducing the pain associated with the procedure.
Last reviewed on RxList: 8/14/2006
This monograph has been modified to include the generic and brand name in many instances.
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