ONYCAL

Terbinafine hydrochloride (Lamisil) is a synthetic allylamine antifungal. 10, 11 It is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues.

Like other allylamines, terbinafine inhibits ergosterol synthesis by inhibiting the fungal squalene monooxygenase (also called squalene epoxidase), an enzyme that is part of the fungal cell wall synthesis pathway. 1, 2, 11 Terbinafine hydrochloride was granted FDA approval on 30 December 1992.

Terbinafine hydrochloride is indicated to treat fungal skin and nail infections caused by Trichophyton species, Microsporum canis, Epidermophyton floccosum, 11 and Tinea species.

Terbinafine hydrochloride also treats yeast infections of the skin caused by Candida species and Malassezia furfur.

Terbinafine is an allylamine antifungal that inhibits squalene epoxidase (also known as squalene monooxygenase) to prevent the formation of ergosterol and cause an accumulation of squalene, weakening the cell wall of fungal cells. 1, 2, 11 Terbinafine distributes into tissues and has a long terminal elimination half life, so the duration of action is long.

Overdose with terbinafine is rare, even above the therapeutic dose, so the therapeutic index is wide. 10, 11 Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.

Oral terbinafine is >70% absorbed but only 40% bioavailable after first pass metabolism, reaching a C max of 1 µg/mL with a T max of 2 hours an an AUC of 4.56 µg*h/mL.

Over the course of a week, 1% topical terbinafine's C max increases from 949-1049ng/cm and the AUC increases from 9694-13,492ng/cm 2 /h.

A single 250 mg oral dose of terbinafine has a volume of distribution at steady state of 947.5 L or 16.6 L/kg.

Terbinafine can be deaminated to 1-naphthaldehyde by CYP2C9, 2B6, 2C8, 1A2, 3A4, and 2C19. 6 1-naphthaldehyde is then oxidized to 1-naphthoic acid or reduced to 1-naphthalenemethanol.

Terbinafine can also be hydroxylated by

CYP1A2, 2C9, 2C8, 2B6, and 2C19 to hydroxyterbinafine.

Hydroxyterbinafine is then oxidized to carboxyterbinafine or N-demethylated by CYP3A4, 2B6, 1A2, 2C9, 2C8, and 2C19 to desmethylhydroxyterbinafine.

Terbinafine can be

N-demethylated to desmethylterbinafine.

Desmethylterbinafine is then dihydroxylated to a desmethyldihydrodiol or hydroxylated to desmethylhydroxyterbinafine.

Finally, terbinafine can be dihydroxylated to a dihydrodiol which is then N-demethylated to a desmethyldihydrodiol.

Hover over products below to view reaction partners Terbinafine Hydroxyterbinafine N-Desmethylhydroxyterbinafine Carboxyterbinafine N-Desmethylterbinafine N-Desmethylterbinafine dihydrodiol derivative N-Desmethylterbinafine dihydrodiol derivative N-Desmethylhydroxyterbinafine 1-Naphthaldehyde 1-Naphthalenemethanol 1-Naphthoic acid Terbinafine dihydrodiol derivative N-Desmethylterbinafine dihydrodiol derivative Terbinafine dihydrodiol derivative N-Desmethylterbinafine dihydrodiol derivative.

Terbinafine is approximately 80% eliminated in urine, while the remainder is eliminated in feces.

The unmetabolized parent drug is not present in urine.

Oral terbinafine has an effective half life of approximately 36 hours.

However, the terminal half life ranges from 200-400 hours as it distributes into skin and adipose tissue. 10 1% topical terbinafine's half life increases over the first seven days from approximately 10-40 hours.

A single 250 mg oral dose of terbinafine has a clearance of 76 L/h or 1.11 L/h/kg.

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The subcutaneous

LD in rats and mice is >2 g/kg.

TDLO for women is 210 mg/kg/6W.

Overdose data with terbinafine is rare, however symptoms are expected to be nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache.

Treat overdose with activated charcoal as well as symptomatic and supportive therapy.

• Chronic or active liver disease.

• History of allergic reaction to oral terbinafine because of the risk of anaphylaxis.

• Prior to administering, evaluate patients for evidence of chronic or active liver disease.

• Fingernail onychomycosis: One tablet, once daily for 6 weeks.

• Toenail onychomycosis: One tablet, once daily for 12 weeks. 2.1 Assessment Prior to Initiation Before administering terbinafine tablets, evaluate patients for evidence of chronic or active liver disease. 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.

USP, 250 mg are supplied as white to off-white, round uncoated, biconvex beveled edge tablets having ‘D’ debossed on one side and ‘74’ on the other side.

Bottles of 30 NDC 68788-7450-03 Bottles of 100 NDC 68788-7450-01 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) .

Protect from light.

Available data from postmarketing cases on the use of terbinafine tablets in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies, terbinafine did not cause malformations or any harm to the fetus when administered to pregnant rabbits and rats during the period of organogenesis at oral doses up to and 23 times the maximum recommended human dose (MRHD) of 250 mg/day, respectively.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

In embryo-fetal development studies in rats and rabbits, pregnant animals received orally (by gavage) doses of terbinafine up to 300 mg/kg/day, during the period of organogenesis.

There were no maternal or embryo-fetal effects in either species up to the maximum dose tested.

The 300 mg/kg/day dose level in rats and rabbits corresponds to and 12 times the MRHD [based on body surface area (BSA) comparisons], respectively.

In a rat peri.

• and postnatal development study, terbinafine doses of up to 300 mg/kg/day (12 times the MRHD based on BSA comparisons) given by oral gavage during late pregnancy and lactation (Day of gestation to day 20 post-partum) had no adverse effects on parturition and lactation.

After oral administration, terbinafine is present in human milk.

However, there are no data on the effects on the breastfed child or on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for terbinafine tablets and any potential adverse effects on the breastfed child from terbinafine tablets or from the underlying maternal condition.

The safety and efficacy of terbinafine tablets have not been established in pediatric patients with onychomycosis.

Clinical studies of terbinafine tablets did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.