LAMISIL- terbinafine hydrochloride tablet
Novartis Pharmaceuticals Corporation
1 INDICATIONS AND USAGE
LAMISIL (terbinafine hydrochloride) Tablets are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium).
Prior to initiating treatment, appropriate nail specimens for laboratory testing [potassium hydroxide (KOH) preparation, fungal culture, or nail biopsy] should be obtained to confirm the diagnosis of onychomycosis.
2 DOSAGE AND ADMINISTRATION
2.1 Assessment Prior to Initiation
? Before administering LAMISIL Tablets, evaluate patients for evidence of chronic or active liver disease [see Contraindications (4) and Warnings and Precautions (5.1)].
2.2 Dosage
Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks.
Toenail onychomycosis: One 250 mg tablet once daily for 12 weeks.
The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.
3 DOSAGE FORMS AND STRENGTHS
Tablet, 250 mg white to yellow-tinged white circular, biconvex, beveled tablets imprinted with "LAMISIL" in circular form on one side and code "250" on the other side.
4 CONTRAINDICATIONS
LAMISIL Tablets are contraindicated in patients with:
� History of allergic reaction to oral terbinafine because of the risk of anaphylaxis [see Adverse Reactions (6.2)]
? � Chronic or active liver disease [see Warnings and Precautions (5.1)]
5 WARNINGS AND PRECAUTIONS
5.1 Hepatotoxicity
? LAMISIL Tablets are contraindicated for patients with chronic or active liver disease. Before prescribing LAMISIL Tablets, perform liver function tests because hepatotoxicity may occur in patients with and without preexisting liver disease. Cases of liver failure, some leading to liver transplant or death, have occurred with the use of LAMISIL Tablets in individuals with and without preexisting liver disease.
11 DESCRIPTION
LAMISIL Tablets contain the synthetic allylamine antifungal compound terbinafine hydrochloride.
Chemically, terbinafine hydrochloride is (E)-N -(6,6-dimethyl-2-hepten-4-ynyl)-N -methyl-1-naphthalenemethanamine hydrochloride. The empirical formula C21 H26 CIN with a molecular weight of 327.90.
Terbinafine hydrochloride is a white to off-white fine crystalline powder. It is freely soluble in methanol and methylene chloride, soluble in ethanol, and slightly soluble in water.
Each tablet contains:
Active Ingredients: terbinafine hydrochloride (equivalent to 250 mg base).
Inactive Ingredients: colloidal silicon dioxide NF, hydroxypropyl methylcellulose USP, magnesium stearate NF, microcrystalline cellulose NF, and sodium starch glycolate NF.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Terbinafine is an allylamine antifungal [see Clinical Pharmacology (12.4) ].
12.2 Pharmacodynamics
The pharmacodynamics of LAMISIL Tablets is unknown.
Microbiology
Terbinafine, an allylamine antifungal, inhibits biosynthesis of ergosterol, an essential component of fungal cell membrane, via inhibition of squalene epoxidase enzyme. This results in fungal cell death primarily due to the increased membrane permeability mediated by the accumulation of high concentrations of squalene but not due to ergosterol deficiency. Depending on the concentration of the drug and the fungal species test in vitro , terbinafine hydrochloride may be fungicidal. However, the clinical significance of in vitro data is unknown.
Terbinafine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections:
Trichophyton mentagrophytes
Trichophyton rubrum
The following in vitro data are available, but their clinical significance is unknown. In vitro , terbinafine exhibits satisfactory MIC's against most strains of the following microorganisms; however, the safety and efficacy of terbinafine in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials:
Candida albicans
Epidermophyton floccosum
Scopulariopsis brevicaulis
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-Approved Medication Guide.
Patients taking LAMISIL Tablets should receive the following information and instructions:
Advise patients to immediately report to their physician or get emergency help if they experience any of the following symptoms: hives, mouth sores, blistering and peeling of skin, swelling of face, lips, tongue, or throat, difficulty swallowing or breathing. LAMISIL Tablets treatment should be discontinued.
Advise patients to immediately report to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. LAMISIL Tablets treatment should be discontinued.
Advise patients to report to their physician any signs of taste disturbance, smell disturbance and/or depressive symptoms, fever, skin eruption, lymph node enlargement, erythema, scaling, loss of pigment, and unusual photosensitivity that can result in a rash. LAMISIL Tablets treatment should be discontinued.
Advise patients to minimize exposure to natural and artificial sunlight (tanning beds or UVA/B treatment) while using LAMISIL Tablets.
Advise patients that if they forget to take LAMISIL Tablets, to take their tablets as soon as they remember, unless it is less than 4 hours before the next dose is due.
Advise patients to call their physician if they take too many LAMISIL Tablets.