terbinafine (as terbinafine hydrochloride) 250 MG Oral Tablet
Generic Name: TERBINAFINE HYDROCHLORIDE
Brand Name: TERBINAFINE HYDROCHLORIDE
- Substance Name(s):
- TERBINAFINE HYDROCHLORIDE
WARNINGS
Rare cases of liver failure, some leading to death or liver transplant, have occurred with the use of terbinafine hydrochloride tablets for the treatment of onychomycosis in individuals with and without pre-existing liver disease.
In the majority of liver cases reported in association with terbinafine hydrochloride tablets use, the patients had serious underlying systemic conditions and an uncertain causal association with terbinafine hydrochloride tablets.
The severity of hepatic events and/or their outcome may be worse in patients with active or chronic liver disease (see PRECAUTIONS).
Treatment with terbinafine hydrochloride tablets should be discontinued if biochemical or clinical evidence of liver injury develops (see PRECAUTIONS below).
There have been isolated reports of serious skin reactions (e.g., Stevens-Johnson Syndrome and toxic epidermal necrolysis).
If progressive skin rash occurs, treatment with terbinafine hydrochloride tablets should be discontinued.
DRUG INTERACTIONS
Drug Interactions In vivo studies have shown that terbinafine is an inhibitor of the CYP450 2D6 isozyme.
Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug classes: tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers, antiarrhythmics class 1C (e.g., flecainide and propafenone) and monoamine oxidase inhibitors Type B.
Coadministration of terbinafine hydrochloride tablets should be done with careful monitoring and may require a reduction in dose of the 2D6-metabolized drug.
In a study to assess the effects of terbinafine on desipramine in healthy volunteers characterized as normal metabolizers, the administration of terbinafine resulted in a 2-fold increase in Cmax and a 5-fold increase in AUC.
In this study, these effects were shown to persist at the last observation at 4 weeks after discontinuation of terbinafine hydrochloride tablets.
In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, and cyclosporine.
In vivo drug-drug interaction studies conducted in healthy volunteer subjects showed that terbinafine does not affect the clearance of antipyrine or digoxin.
Terbinafine decreases the clearance of caffeine by 19%.
Terbinafine increases the clearance of cyclosporine by 15%.
There have been spontaneous reports of increase or decrease in prothrombin times in patients concomitantly taking oral terbinafine and warfarin, however, a causal relationship between terbinafine hydrochloride tablets and these changes has not been established.
Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor.
Terbinafine clearance is unaffected by cyclosporine.
There is no information available from adequate drug-drug interaction studies with the following classes of drugs: oral contraceptives, hormone replacement therapies, hypoglycemics, theophyllines, phenytoins, thiazide diuretics, and calcium channel blockers.
OVERDOSAGE
Clinical experience regarding overdose with terbinafine hydrochloride tablets is limited.
Doses up to 5 grams (20 times the therapeutic daily dose) have been taken without inducing serious adverse reactions.
The symptoms of overdose included nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache.
DESCRIPTION
Terbinafine hydrochloride 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 C21H26ClN with a molecular weight of 327.90, and the following structural formula: Terbinafine hydrochloride is a white to off-white 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: microcrystalline cellulose, NF; hypromellose 6 cps, USP; sodium starch glycolate, NF; colloidal silicon dioxide, NF; magnesium stearate, NF Structure
CLINICAL STUDIES
The efficacy of terbinafine hydrochloride tablets in the treatment of onychomycosis is illustrated by the response of patients with toenail and/or fingernail infections who participated in three US/Canadian placebo-controlled clinical trials.
Results of the first toenail study, as assessed at week 48 (12 weeks of treatment with 36 weeks follow-up after completion of therapy), demonstrated mycological cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 70% of patients.
Fifty-nine percent (59%) of patients experienced effective treatment (mycological cure plus 0% nail involvement or >5mm of new unaffected nail growth); 38% of patients demonstrated mycological cure plus clinical cure (0% nail involvement).
In a second toenail study of dermatophytic onychomycosis, in which non-dermatophytes were also cultured, similar efficacy against the dermatophytes was demonstrated.
The pathogenic role of the non-dermatophytes cultured in the presence of dermatophytic onychomycosis has not been established.
The clinical significance of this association is unknown.
Results of the fingernail study, as assessed at week 24 (6 weeks of treatment with 18 weeks follow-up after completion of therapy), demonstrated mycological cure in 79% of patients, effective treatment in 75% of the patients, and mycological cure plus clinical cure in 59% of the patients.
The mean time to overall success was approximately 10 months for the first toenail study and 4 months for the fingernail study.
In the first toenail study, for patients evaluated at least six months after achieving clinical cure and at least one year after completing terbinafine hydrochloride tablets therapy, the clinical relapse rate was approximately 15%.
HOW SUPPLIED
Terbinafine hydrochloride tablets 250 mg, supplied as white circular, bi-convex, bevelled tablets embossed with ‘W’ on one side and ‘743’ on other side.
Bottles of 30 tablets…………………………..NDC 64679-743-01 Bottles of 1000 tablets……………………….NDC 64679-743-02 Bottles of 100 tablets…………………………NDC 64679-743-03 Cartons of 1 blister card (30 tablets) ……NDC 64679-743-05 Store at 20° – 25 °C (68° – 77 ° F); in a tight container.
Protect from light.
INDICATIONS AND USAGE
Terbinafine hydrochloride tablets are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium) (see DOSAGE AND ADMINISTRATION and CLINICAL STUDIES).
Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis.
PEDIATRIC USE
Pediatric Use The safety and efficacy of terbinafine hydrochloride tablets have not been established in pediatric patients.
PREGNANCY
Pregnancy Pregnancy Category B: Oral reproduction studies have been performed in rabbits and rats at doses up to 300 mg/kg/day (12x to 23x the MRHD, in rabbits and rats, respectively, based on BSA) and have revealed no evidence of impaired fertility or harm to the fetus due to terbinafine.
There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, and because treatment of onychomycosis can be postponed until after pregnancy is completed, it is recommended that terbinafine hydrochloride tablets not be initiated during pregnancy.
NUSRING MOTHERS
Nursing Mothers After oral administration, terbinafine is present in breast milk of nursing mothers.
The ratio of terbinafine in milk to plasma is 7:1.
Treatment with terbinafine hydrochloride tablets is not recommended in nursing mothers.
DOSAGE AND ADMINISTRATION
Terbinafine hydrochloride tablets, one 250 mg tablet, should be taken once daily for 6 weeks by patients with fingernail onychomycosis.
Terbinafine hydrochloride tablets, one 250 mg tablet, should be taken once daily for 12 weeks by patients with toenail onychomycosis.
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.