MEDICAL INFORMATION
DESCRIPTION
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.
COMPOSITION
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:
MECHANISM OF ACTION
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.
PHARMACOKINETICS
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.
INDICATION AND USAGE
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.
CONTRAINDICATION
TOPICAINE® is contraindicated in patients with sensitivity
to the amide type local anesthetics or to any other component of the product.
WARNINGS
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.
PRECAUTIONS
General:
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.
Information for patients:
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.
Drug interactions:
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.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Carcinogenesis:
Metabolites of lidocaine have been shown to be carcinogenic in
laboratory animals. A two-year oral toxicity study of 2,6-xylidine, a metabolite 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.
Mutagenesis:
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.
Use in Pregnancy: Teratogenic Effects: Pregnancy Category B
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.
Labor and delivery:
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.
Nursing mothers:
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.
Pediatric use:
Consult a doctor. Observe child during application to avoid
accidental ingestion. Not for otic or ophtalmic use.
ADVERSE REACTIONS
Localized reactions:
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 Reactions:
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.
IMPORTANT
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.
HOW SUPPLIED
TOPICAINE®
4% is supplied in the USA as: 1/3 Oz
(10 g) tubes; 1 Oz (30 g) tubes and 4 Oz (113 g) flexible bottles. 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 centigrade
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) FLEXIBLE BOTTLES,
CHILD RESISTANT PACKAGING
Manufactured for:
ESBA Laboratories Inc.
1001 Jupiter Park Dr Ste 112
Jupiter FL 33458
MADE IN USA
Customer Service:
(800) 677-9299
TOPICAINE is a trademark and product of Esba Laboratories Inc. |