Lamisil (Terbinafine)

Terbinafine is a systemic (oral) allylamine antifungal that inhibits squalene epoxidase. This blocks ergosterol production and causes squalene to build up inside the fungal cell, which leads to fungal cell death. Terbinafine (Lamisil) 250 mg tablets are used to treat dermatophyte onychomycosis of the toenails or fingernails.

Terbinafine (Lamisil) 250 mg tablets are a synthetic allylamine antifungal that is structurally similar to naftifine.

Terbinafine (Lamisil) 250 mg tablets are well absorbed (>70%), but bioavailability is about 40% because of first-pass metabolism. In plasma, more than 99% of terbinafine is bound to plasma proteins. The effective half-life is ~36 hours; a terminal half-life of 200 to 400 hours may reflect slow elimination from tissues such as the skin and adipose tissue. Terbinafine is distributed to the sebum and skin.

LAMISIL Tablets are contraindicated in patients with chronic or active liver disease. Use has not been adequately studied in patients with renal impairment (creatinine clearance ≤ 50 mL/min). Rifampin increases terbinafine clearance, and cimetidine decreases terbinafine clearance. The drug is generally well tolerated, but rare serious side effects can include hepatotoxicity, severe neutropenia, Stevens-Johnson syndrome, toxic epidermal necrolysis, and other serious skin reactions.

Available human data are not sufficient to assess a drug-related risk in pregnancy. Because treatment of onychomycosis can usually be delayed, discuss use during pregnancy with a healthcare provider.

Terbinafine (Lamisil) 250 mg is taken as one 250 mg tablet once daily. Fingernail onychomycosis: 6 weeks. Toenail onychomycosis: 12 weeks. The best clinical effect is usually seen several months after mycologic cure and the end of treatment, as healthy nail grows out. In Canada, oral terbinafine tablets are approved for onychomycosis; use for other fungal infections may be considered off-label.

Terbinafine Hydrochloride: Uses

Onychomycosis

Terbinafine is taken by mouth to treat dermatophyte infections of the toenails or fingernails (onychomycosis, tinea unguium) caused by susceptible fungi. Before starting oral terbinafine, appropriate nail samples should be collected for microbiologic testing, such as potassium hydroxide [KOH] preparation, fungal culture, or nail biopsy, to confirm the diagnosis of onychomycosis. The full clinical benefit of terbinafine in onychomycosis is usually seen several months after mycologic cure and the end of treatment, because healthy nail needs time to grow out.

Because terbinafine is highly lipophilic and keratophilic, it reaches high concentrations in the stratum corneum, sebum, hair, and the nail matrix, bed, and plate. It can remain in these tissues for several weeks to months after the drug is stopped. Toenail infections generally need longer treatment with terbinafine than fingernail infections.

The effectiveness of terbinafine has been established in uncontrolled studies and in studies comparing it with placebo or other antifungal drugs in patients with toenail or fingernail onychomycosis. In these studies, patients were assessed for mycologic cure (negative microscopy of lesion scrapings prepared with potassium hydroxide and negative culture of lesion scrapings), effective treatment (mycologic cure and either no nail involvement or more than 5 mm of unaffected new nail growth), or mycologic and clinical cure (no nail involvement). Terbinafine has been shown to be active against most strains of Trichophyton rubrum and T. mentagrophytes both in vitro and in clinical nail infections. Although terbinafine is active in vitro against most strains of Epidermophyton floccosum, Candida albicans, and Scopulariopsis brevicaulis, its effectiveness in treating onychomycosis caused by these organisms has not yet been established in controlled clinical studies.

In toenail studies, 12 weeks of oral terbinafine 250 mg daily was more effective than placebo or itraconazole 200 mg daily, and 16 weeks of oral terbinafine at this dosage was more effective than up to 52 weeks of oral griseofulvin 500 mg daily. In these studies, 70-88% of patients had mycologic cure, 59% had effective treatment, and 38-57% had mycologic and clinical cure when evaluated 36-48 weeks after completing terbinafine treatment. The clinical relapse rate was about 15% in those assessed at least 6 months after clinical cure and at least 1 year after completing terbinafine treatment.

In a study comparing 4 months of continuous oral terbinafine (250 mg daily), intermittent oral terbinafine (500 mg daily for 1 week each month), and intermittent oral itraconazole (400 mg daily for 1 week each month), there was a trend favouring continuous terbinafine therapy, but no statistically significant differences in cure rates were found between the regimens. In a study comparing treatment durations of 6, 12, and 24 weeks in patients with toenail infections, mycologic cure rates were substantially higher with the 12- and 24-week regimens than with the 6-week regimen, but the 24-week regimen was not substantially more effective than the 12-week regimen. However, some patients who do not respond to an initial 12-week course of terbinafine may respond to a second course.

In fingernail studies, 75% of patients had effective treatment, and 59-90% had mycologic and clinical cure when assessed 18-42 weeks after completing 6 weeks of oral terbinafine 250 mg daily. Extending treatment to 12 weeks in patients with fingernail infections does not appear to improve response substantially. In one study of patients with fingernail onychomycosis who received oral terbinafine 250 mg daily for 2 or 4 weeks, 65% had mycologic and clinical cure 6 months after treatment ended; the cure rate in those who received only 2 weeks of therapy was 45%.

However, liver failure, sometimes leading to death or liver transplant, has rarely occurred in patients with or without pre-existing liver disease who were taking terbinafine for onychomycosis. Before starting oral terbinafine, patients should be assessed for liver disease; pretreatment measurement of serum ALT (SGPT) and AST (SGOT) is advised for all patients.

Terbinafine should be stopped if biochemical or clinical signs of liver injury develop during treatment. Patients should be told to report any signs or symptoms of liver problems, such as persistent nausea, loss of appetite, fatigue, vomiting, pain in the upper right abdomen, jaundice, dark urine, or pale stools. Patients with these signs or symptoms should stop terbinafine and have their liver function checked right away.

Other uses

In Canada, terbinafine tablets are approved for onychomycosis. Use for other fungal infections may be considered off-label and should be guided by a healthcare provider. The safety and effectiveness of LAMISIL Tablets have not been established in pediatric patients.

Terbinafine: Organs and Systems

Sensory systems

Taste disturbance is a rare side effect of terbinafine. It is usually reversible, with a median time to recovery of 42 days. However, prolonged or persistent taste disturbances have been reported.

Hematologic

Pancytopenia has been reported.

Leukocytes

Neutropenia has been reported in patients taking terbinafine.

• A 55-year-old woman taking terbinafine and paroxetine presented with fever, diarrhea, and vomiting. A bone marrow biopsy showed overall reduced cellularity, and the aspirate showed a profound shift toward the production of immature myeloid cells, consistent with maturation arrest. Treatment included stopping all outpatient medications, hydration, intravenous fluids, broad-spectrum antibiotics, and G-CSF 5 µg/kg for 5 days. Mature granulocytes appeared in the peripheral blood on the fifth day in hospital, and she was discharged on the seventh hospital day with an absolute neutrophil count of 6.2 x 10⁹/L. Paroxetine was resumed weeks after discharge without hematologic toxicity over 6 months.
• A 60-year-old man presented with fever, oral mucositis, pedal cellulitis, and bacteremia after a 6-week course of terbinafine 250 mg. He was also taking yohimbine for impotence. Bone marrow examination showed a hypocellular marrow with myeloid maturation arrest. Treatment included stopping outpatient medications, broad-spectrum antibiotics, hydration, and G-CSF, and was ultimately successful. Yohimbine was resumed later without any side effects.
• A 42-year-old man presented with fever and granulocytopenia (absolute neutrophil count: 340 x 10⁶/L; temperature: 40°C (103.1°F)) after a 30-day course of oral terbinafine 250 mg/day for presumed onychomycosis. The granulocyte count recovered promptly after the drug was stopped and G-CSF was given for 2 days.
• Agranulocytosis occurred in a 15-year-old who took terbinafine 250 mg/day for toenail onychomycosis and tinea pedis. This effect was noted 4 weeks after starting terbinafine and resolved within 1 week after it was stopped.

Platelets

Thrombocytopenia has been attributed to terbinafine.

• A 25-year-old Yemeni woman with familial-ethnic leukopenia developed thrombocytopenia with epistaxis after taking terbinafine 250 mg for 4 weeks. The platelet count recovered from a nadir of 63 x 10⁹/L to 314 x 10⁹/L after the drug was stopped.
• A 53-year-old woman developed severe thrombocytopenia after a 6-week course of terbinafine (250 mg/day) for onychomycosis. A bone marrow aspirate showed a normocellular marrow. She received a platelet transfusion and recovered after a short course of prednisolone.

Mouth

• A 38-year-old man presented with acute right otitis media and unrelated painless bilateral enlargement of the parotid glands 15 days after taking oral terbinafine for tinea cruris. He stopped taking terbinafine, and 12 days later the swelling had significantly improved; it disappeared completely 4 weeks later.

Liver

Minor abnormalities in liver function tests have been reported in patients taking oral terbinafine. Terbinafine can cause hepatitis, and rare cases of liver failure have been reported.

Skin

Skin side effects have been reported in patients taking terbinafine. Most of these reactions are mild to moderate macular rashes.

Generalized rashes, fixed drug eruptions, toxic epidermolysis, and erythema exudativum multiforme have all been reported with terbinafine.

Storage

Store below 25°C (77°F) in a tightly closed container. Protect from light.