terbinafine hydrochloride
Lamisil, Lamisil AT, Lamisil DermGel

Available forms
Available by prescription only
Cream: 1%
Gel: 1% (10mg/g)
Tablets: 250 mg
Available without a prescription
Cream: 1%
Spray: 1%

Indications and dosages
 Interdigital tinea pedis, tinea cruris, or tinea corporis caused by Epidermophyton floccosum, Trichophyton mentagrophytes, or I. rubum. Adults and children older than age 12: For interdigital tinea pedis, apply to cover the affected and immediately surrounding areas b.i.d. until signs and symptoms significantly improve (by day 7 for most patients). For tinea cruris or tinea corporis, apply to cover the affected and immediately surrounding areas once or twice daily until signs and symptoms significantly improve (by day 7 for most patients). Treatment should last at least 1 week and no longer than 4 weeks.
 Onychomycosis of fingernails or toenails caused by dermatophytes (tinea unguium). Adults and children older than age 12: For fingernails, 250 mg P.O. daily for 6 weeks. For toenails, 250 mg P.O. daily for 12 weeks.

Pharmacodynamics
Antifungal action: Terbinafine exerts its antifungal effect by inhibiting squalene epoxidase, a key enzyme in sterol biosynthesis in fungi. This action results in a deficiency in ergosterol and a corresponding accumulation of squalene within the fungal cell and causes fungal cell death.

Pharmacokinetics
Absorption: Topical form
Absorption: Systemic absorption of terbinafine is highly variable.
Distribution: No information available.
Metabolism: No information available.
Excretion: About 75% of cutaneously absorbed terbinafine is eliminated in urine, predominantly as metabolites.
Absorption: Oral form
Absorption: More than 70% of drug is absorbed; food enhances absorption.
Distribution: Distributed to serum and skin. Plasma half-life is about 36 hours; half-life in tissue is 200 to 400 hours. More than 99% of drug is bound to plasma proteins.
Metabolism: First-pass metabolism is about 40%.
Excretion: About 70% of dose is eliminated in urine; clearance is decreased by 50% in patients with hepatic cirrhosis and impaired renal function.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Oral form is also contraindicated in pregnant women and in patients with hepatic disease or impaired renal function (creatinine clearance of 50 ml/minute or less).

Interactions
Drug-drug. None reported for topical form.
Cimetidine: Decreases terbinafine clearance by 33%. Avoid use together.
Cyclosporine: Increases cyclosporine clearance. Monitor levels carefully.
I.V. caffeine: Decreases caffeine clearance. Monitor patient closely.
Rifampin: Increases terbinafine clearance by 100%. Monitor patient closely.

Adverse reactions
CNS: headache.
EENT: visual disturbances.
GI: taste disturbances, diarrhea, dyspepsia, abdominal pain, nausea, flatulence.
Hematologic: decreased absolute lymphocyte count, neutropenia.
Skin: Stevens-Johnson syndrome, toxic epidermal necrolysis, irritation, burning, pruritus, dryness, rash, pruritus.

Effects on lab test results
• May increase liver enzyme levels.
• May decrease neutrophil and lymphocyte counts.

Overdose and treatment
Acute overdose with topical application is unlikely because of the limited absorption of topically applied drug and wouldn’t be expected to lead to a life-threatening situation.

Special considerations
 ALERT Don’t confuse terbinafine and terbutaline.
• Before initiating treatment, obtain appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) to confirm the diagnosis of onychomycosis.
• Don’t use topical form for oral, ophthalmic, or intravaginal use.
• Tests of serum AST and ALT levels are advised for all patients before therapy starts.
• Many patients given shorter durations of therapy (1 to 2 weeks) continue to improve during the 2 to 4 weeks after drug therapy stops. Therefore, therapy shouldn’t be considered a failure until patient has been observed for 2 to 4 weeks off therapy. If successful outcome isn’t achieved during the post-treatment observation period, review the diagnosis.
• Monitor patient for irritation or sensitivity to drug. Discontinue therapy if irritation or sensitivity is present, and institute appropriate treatment measures.
 ALERT Rare cases of liver failure, some leading to death or liver transplant, have occurred with the use of tablets in individuals with and without preexisting liver disease. Tablets aren’t recommended for patients with chronic or active liver disease.
• If persistent nausea, anorexia, fatigue, vomiting, right upper quadrant abdominal pain, jaundice, dark urine, or pale stools occur, discontinue treatment and obtain liver function tests.
Pregnant patients
• Not recommended for use during pregnancy.
Breast-feeding patients
• Drug appears in breast milk. A decision to discontinue either breast-feeding or drug must be made, taking into account the importance of drug to the woman.
• Women who are breast-feeding should avoid applying terbinafine cream to the breast.
Pediatric patients
• Safety and efficacy in children younger than age 12 haven’t been established.

Patient education
• Advise patient to use drug as directed and to avoid contact with eyes, nose, mouth, or other mucous membranes.
• Stress importance of using drug for recommended treatment time.
 ALERT If patient takes tablets, tell him to report persistent nausea, anorexia, fatigue, vomiting, right upper quadrant abdominal pain, jaundice, dark urine, or pale stool.
• Tell patient to report if the area of application shows signs or symptoms of increased irritation or possible sensitization, such as redness, itching, burning, blistering, swelling, or oozing.
• Instruct patient not to use occlusive dressings unless directed.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use