Prescription Drug Information: Lidocaine

LIDOCAINE- lidocaine patch
Actavis Pharma, Inc.

Lidocaine Patch 5%
Rx Only

DESCRIPTION

Lidocaine patch 5% is comprised of an adhesive material containing 5% lidocaine, USP, which is applied to a white non-woven polyethylene terephthalate (PET) material backing and covered with a transparent PET release liner. The release liner is removed prior to application to the skin. The size of the patch is 10 cm x 14 cm.

Lidocaine, USP is chemically designated as acetamide, 2-(diethylamino)-N-(2,6- dimethylphenyl), has an octanol:water partition ratio of 43 at pH 7.4, and has the following structure:

chemical structure for lidocaine

Each adhesive patch contains 700 mg of lidocaine, USP (50 mg per gram adhesive) in an aqueous base. It also contains the following inactive ingredients: glycerin, D-sorbitol, propylene glycol, polyvinyl alcohol, urea, sodium polyacrylate, carboxymethylcellulose sodium, gelatin, polyacrylic acid, kaolin, tartaric acid, dihydroxyaluminum aminoacetate, methylparaben, propylparaben, and edetate disodium.

CLINICAL PHARMACOLOGY

Pharmacodynamics

Lidocaine is an amide-type local anesthetic agent and is suggested to stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses.

The penetration of lidocaine into intact skin after application of lidocaine patch is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block.

Pharmacokinetics

Absorption:

The amount of lidocaine systemically absorbed from lidocaine patch is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three lidocaine patches were applied over an area of 420 cm2 of intact skin on the back of normal volunteers for 12 hours. Blood samples were withdrawn for determination of lidocaine concentration during the application and for 12 hours after removal of patches. The results are summarized in Table 1.

Table 1 Absorption of lidocaine from Lidocaine Patch Normal volunteers (n= 15, 12-hour wearing time)
Lidocaine Patch Application Site Area (cm2) Dose Absorbed (mg) Cmax (mcg/mL) Tmax (hr)
3 patches(2100 mg) Back 420 64 ± 32 0.13 ± 0.06 11 hr

When lidocaine patch is used according to the recommended dosing instructions, only 3 ± 2% of the dose applied is expected to be absorbed. At least 95% (665 mg) of lidocaine will remain in a used patch. Mean peak blood concentration of lidocaine is about 0.13 mcg/mL (about 1/10 of the therapeutic concentration required to treat cardiac arrhythmias). Repeated application of three patches simultaneously for 12 hours (recommended maximum daily dose), once per day for three days, indicated that the lidocaine concentration does not increase with daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers is shown in Figure 1.

Figure 1 Mean lidocaine blood concentrations after three consecutive daily applications of three lidocaine patches simultaneously for 12 hours per day in healthy volunteers (n = 15).
(click image for full-size original)

Figure 1 Mean lidocaine blood concentrations after three consecutive daily applications of three lidocaine patches simultaneously for 12 hours per day in healthy volunteers (n = 15).

Distribution:

When lidocaine is administered intravenously to healthy volunteers, the volume of distribution is 0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n=15). At concentrations produced by application of lidocaine patch, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 mcg/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.

Metabolism:

It is not known if lidocaine 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. A minor metabolite, 2, 6-xylidine, has unknown pharmacologic activity but is carcinogenic in rats. The blood concentration of this metabolite is negligible following application of lidocaine patch 5%. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively.

Excretion:

Lidocaine and its metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted unchanged. The half-life of lidocaine elimination from the plasma following IV administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic clearance is 0.33 to 0.90 L/min (mean 0.64 ± 0.18 SD, n = 15).

CLINICAL STUDIES

Single-dose treatment with lidocaine patch was compared to treatment with vehicle patch (without lidocaine), and to no treatment (observation only) in a double-blind, crossover clinical trial with 35 post-herpetic neuralgia patients. Pain intensity and pain relief scores were evaluated periodically for 12 hours. Lidocaine patch performed statistically better than vehicle patch in terms of pain intensity from 4 to 12 hours.

Multiple-dose, two-week treatment with lidocaine patch was compared to vehicle patch (without lidocaine) in a double-blind, crossover clinical trial of withdrawal-type design conducted in 32 patients, who were considered as responders to the open-label use of lidocaine patch prior to the study. The constant type of pain was evaluated but not the pain induced by sensory stimuli (dysesthesia). Statistically significant differences favoring lidocaine patch were observed in terms of time to exit from the trial (14 versus 3.8 days at p-value less than 0.001), daily average pain relief, and patient’s preference of treatment. About half of the patients also took oral medication commonly used in the treatment of post-herpetic neuralgia. The extent of use of concomitant medication was similar in the two treatment groups.

INDICATION AND USAGE

Lidocaine patch 5% is indicated for relief of pain associated with post-herpetic neuralgia. It should be applied only to intact skin.

CONTRAINDICATIONS

Lidocaine patch 5% is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product.

WARNINGS

Risk of Methemoglobinemia

Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.

Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue lidocaine and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

Accidental Exposure in Children

Even a used lidocaine patch contains a large amount of lidocaine (at least 665 mg). The potential exists for a small child or a pet to suffer serious adverse effects from chewing or ingesting a new or used lidocaine patch, although the risk with this formulation has not been evaluated. It is important for patients to store and dispose of lidocaine patch 5% out of the reach of children, pets and others. (See HANDLING AND DISPOSAL)

Excessive Dosing

Excessive dosing by applying lidocaine patch 5% to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious adverse effects (see ADVERSE REACTIONS, Systemic Reactions). Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. With recommended dosing of lidocaine patch 5%, the average peak blood concentration is about 0.13 mcg/mL, but concentrations higher than 0.25 mcg/mL have been observed in some individuals.

PRECAUTIONS

General

Hepatic Disease: Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of lidocaine, because of their inability to metabolize lidocaine normally.

Allergic Reactions: Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine. However, lidocaine patch 5% should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.

Non-intact Skin: Application to broken or inflamed skin, although not tested, may result in higher blood concentrations of lidocaine from increased absorption. Lidocaine patch 5% is only recommended for use on intact skin.

External Heat Sources: Placement of external heat sources, such as heating pads or electric blankets, over lidocaine patch 5% is not recommended as this has not been evaluated and may increase plasma lidocaine levels.

Eye Exposure: The contact of lidocaine patch 5% with eyes, although not studied, should be avoided based on the findings of severe eye irritation with the use of similar products in animals. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.

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