TOPICAINE® is a hydro-ethanolic, non-oily, translucent microemulsion gel containing lidocaine 4% with skin permeation enhancers and soothing agents, indicated as a topical anesthetic for use on normal intact skin for local analgesia.
Each gram of TOPICAINE® contains lidocaine 40 mg in a gel composed of water, ethanol (35% w/w), glycerin, jojoba oil, aloe vera oil, glyceryl monolaurate, benzyl alcohol, carbomer 940, EDTA. TOPICAINE® has a pH of 7.5.
The chemical designation of Lidocaine (syn. Lignocaine) is 2-(diethylamino)-N(2,6-dimethylphenyl), acetamide; MP 68-69 degrees centigrades ; MW 234.33. It has the following structure:
TOPICAINE® applied to intact skin provides dermal analgesia by the release of lidocaine from the gel into the epidermis and dermis. Lidocaine is a local anesthetic agent of the amide type. Local anesthetics reversibly block the initiation and conduction of nerve impulses by interfering with the flux of sodium ions though the neuronal membrane. The onset, depth and duration of dermal analgesia provided by TOPICAINE® depend primarily on the site of application and duration of application. Adequate dermal analgesia is obtained after 1 hour of application, and the effect persists for approximately 1 hour after removal. Areas such as the upper lip may be numb after 30 minutes of application. Dermal application of TOPICAINE® may cause local blanching followed by local redness or erythema. These effects are mild and transitory.
TOPICAINE® is formulated to insure good local penetration of lidocaine into the skin. A side effect of this desired local effect may be the systemic absorption of lidocaine.The systemic absorption of lidocaine from TOPICAINE® has not been determined in clinical studies, but information available in the literature indicates that the amount of lidocaine systemically absorbed is directly related to both the duration of application and to the area over which it is applied. By inference from published clinical studies, the application of TOPICAINE® to broken or inflamed skin, or to 2,000 cm2 or more of skin of an adult, (600 cm2 in children 10-20 kg body weight, 100 cm2 in children up to 10 kg) could result in plasma levels that could, in susceptible individuals, produce a systemic pharmacologic response. Patients receiving lidocaine by prolonged infusion (for suppression of ventricular dysrhythmias) present objective systemic toxic effects at plasma concentrations of 6-10 m g/ml. When lidocaine is administered intravenously, it distributes to highly perfused organs such as brain, liver, kidney and heart. Lidocaine bounds to plasma proteins (approx. 70%). It can cross the placental and blood brain barrier, presumably by passive diffusion. It is not known whether lidocaine is metabolized in the skin. When administered intravenously it is metabolized by the liver. The major metabolites are monoethylglycylxylidide (MEGX) and glycylxylidide (GX). The biological half-life of lidocaine is 1.5 hrs; its plasma clearance averages 1 lt/min and is dependent on liver blood flow. Both MEGX and GX have pharmacologic effects, both as antiarrythmics and in terms of toxicity.
TOPICAINE®(lidocaine 4%) is indicated for the temporary relief of pain and itching. It is a topical analgesic for use on normal intact skin for local pain relief.
TOPICAINE® is not recommended for use on mucous membranes because of much greater absorption than through intact skin. TOPICAINE® is not recommended for use beyond the external ear. Not for ophtalmic use.
TOPICAINE® is contraindicated in patients with sensitivity to the amide type local anesthetics or to any other component of the product.
For external use only. Avoid contact with the eyes. Do not use over large areas of the body. Do not use for more than 7 days unless directed by a doctor. Keep this and all drugs out of the reach of children. In case of accidental ingestion, seek professional assistance or contact a Poison Control Center immediately.
Inappropriate use of this product, such as application on mucous membranes, on large areas of the body, or on individuals that are allergic to the amide type anesthetics, may result in serious side effects. Consultation with a doctor before using this product is strongly recommended.
Repeated doses of TOPICAINE® may increase blood levels of lidocaine. Avoid contact with the eye since it may cause severe irritation and loss of protective reflexes. If eye contact occurs, immediately wash out the eye with water or saline. Patients with severe hepatic disease are at a greater risk of developing toxic plasma concentrations of lidocaine.
When TOPICAINE® is used the patient should be aware that the production of dermal analgesia may be accompanied by the block of all sensations in the treated skin. For this reason, the patient should avoid inadvertent trauma to the treated area by scratching, rubbing or exposure to extreme hot or cold temperatures until complete sensation has returned.
TOPICAINE® should be used with caution in patients receiving Class I antiarrythmic agents (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic.
Metabolites of lidocaine have been shown to be carcinogenic in laboratory animals. A two-year oral toxicity study of 2,6-xylidine, ametabolite of lidocaine, has shown that in both male and female rats daily doses of 900 mg/m2 (60 times SDA) resulted in adenomas and carcinomas of the nasal cavity. With daily doses of 300 mg/m2 (20 times SDA) the increase in incidence of nasal carcinomas and or adenomas in each sex of the rat were not statistically greater than the control group. In the low dose (90 mg/m2, 6 times SDA) and control groups, no nasal tumors were observed.
The mutagenic potential of lidocaine HCl has been tested in the Ames Salmonella -mammalian microsome test and by analysis of structural chromosome aberrations in human lymphocites in vitro, and by the mouse micronuclear test in vivo. There was no indication in these three tests of any mutagenic effects. The mutagenicity of 2,6-xylidine, a metabolite of lidocaine has been studied in different tests with mixed results. The compound was found to be weakly mutagenic in the Ames test only under metabolic activation conditions. In addition, 2,6-xylidine was observed to be mutagenic at the thymidine kinase locus, with or without activation, and induced chromosome aberrations and sister chromatid exchanges at concentrations in which the drug precipitated out of solution (1.2 mg/ml). No evidence of genotoxicity was found in the in vivo assays measuring unscheduled DNA synthesis in rat hepatocytes, chromosome damage in polychromateic erythrocytes or preferential killing of DNA repair-deficient bacteria in liver, lung kidney, testes and blood extracts from mice. However covalent binding studies of DNA from liver and ethmoid turbinates in rats indicate that 2,6 xylidine may be genotoxic under certain conditions in vivo.
Reproduction studies with lidocaine have been performed in rats and have revealed no evidence of harm to the fetus (30 mg/kg subcutaneously, 22 times SDA). There are however, no adequate and well-controlled studies on pregnant women. Therefore TOPICAINE® should be used in pregnancy only under a doctor’s supervision.
Lidocaine is not contraindicated in labor and delivery. Should TOPICAINE® be used concomitantly with other products containing lidocaine, total doses contributed by all formulations must be considered.
Lidocaine is excreted in human milk, therefore, caution should be exercised when TOPICAINE® is administered to a nursing mother since the milk:plasma ratio of lidocaine is 0.4.
Consult a doctor. Observe child during application to avoid accidental ingestion. Not for otic or ophtalmic use.
During or immediately after treatment with TOPICAINE® the skin at the site of treatment may develop erythema or edema or may be the locus of abnormal sensation. These effects are mild and transient, resolving spontaneously within 1 or 2 hours. Other common effects is paleness (pallor or blanching) when the application time is very prolonged (over 2 hours), and less frequently alterations in temperature sensations, edema, itching and rash.
Allergic and anaphylactoid reactions associated with lidocaine can occur. They are characterized by urticaria, angioedema, bronchospasm, and shock.
Systemic (Dose Related) Reactions:
Systemic adverse reactions following appropriate use of TOPICAINE® are unlikely due to the small dose absorbed. Systemic adverse effects of lidocaine are similar in nature to those observed with other amide type local anesthetics including CNS excitation and/or depression (light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest). Cardiovascular manifestations may include bradycardia, hypotension and cardiovascular collapse leading to arrest.
NOT FOR OPHTHALMIC USE
KEEP CONTAINER CLOSED AT ALL TIMES WHEN NOT IN USE. KEEP OUT OF THE REACH OF CHILDREN.
PATCH TEST RECOMMENDED:
As with any topical, it is recommended that a patch test be performed to rule out any untoward effects. Apply on a small, inconspicuous area and observe for 24 hours. Preferably repeat this patch test 7 days after the initial one.
TOPICAINE® 4% is supplied in the USA as: 1/3 Oz (10 g) tubes; 1 Oz (30 g) tubes and 4 Oz (113 g) tubes.
Please note that containers are filled by weight, not volume. Air bubbles may be present in the gel. Store at controlled room temperature 15-30 degrees Celsius.
NDC # 63135-312-13 (1/3 Oz) (10 g) TUBES ; CHILD RESISTANT PACKAGING
NDC # 63135-312-30 (1 Oz) (30 g) TUBES, CHILD RESISTANT PACKAGING
NDC # 63135-312-04 (4 Oz) (113 g) TUBES, CHILD RESISTANT PACKAGING
ESBA Laboratories Inc.1001 Jupiter Park Dr Ste 112Jupiter FL 33458MADE IN USA
TOPICAINE® is a trademark and product of Esba Laboratories Inc.