Lamisil (Terbinafine)

Terbinafine is a systemic (oral) allylamine antifungal that inhibits squalene epoxidase. This blocks ergosterol biosynthesis and causes squalene to build up within the fungal cell, leading to fungal cell death. Terbinafine (Lamisil) 250 mg tablets are indicated for the treatment of onychomycosis of the toenail or fingernail caused by dermatophytes.

Terbinafine (Lamisil) 250 mg tablets are a synthetic allylamine antifungal, 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). Rifampicin 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 insufficient to assess a drug-associated risk in pregnancy; because treatment of onychomycosis can usually be postponed, discuss use during pregnancy with an Australian healthcare professional. In Australia, this is usually a discussion with your GP, dermatologist or pharmacist before starting treatment.

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

Terbinafine Hydrochloride: Uses

Onychomycosis

Terbinafine is used orally to treat dermatophyte infections of the toenail or fingernail (onychomycosis, tinea unguium) caused by susceptible fungi. Before starting oral terbinafine, appropriate nail samples for microbiological studies (for example, potassium hydroxide [KOH] preparation, fungal culture or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. The best clinical effect of terbinafine in the treatment of onychomycosis is seen several months after mycological cure and completion of treatment, and reflects the time needed for healthy nail 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, and persists in these tissues for several weeks to months after treatment is stopped. Toenail infections generally require a longer course of terbinafine than fingernail infections.

The efficacy of terbinafine has been established in uncontrolled studies and in placebo-controlled or active-comparator studies in patients with toenail or fingernail onychomycosis. In these studies, patients were assessed for mycological cure (negative observation of fungus in lesion scrapings prepared with potassium hydroxide, and negative culture of lesion scrapings), effective treatment (mycological cure and either no nail involvement or more than 5 mm of unaffected new nail growth), or mycological 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, the efficacy of the drug in the treatment of onychomycosis caused by these organisms remains to be established in controlled clinical studies.

In toenail studies, 12 weeks of oral therapy with terbinafine 250 mg daily was more effective than placebo or itraconazole 200 mg daily, and 16 weeks of oral terbinafine therapy at this dosage was more effective than up to 52 weeks of oral griseofulvin 500 mg daily. In these studies, 70-88% of patients experienced mycological cure, 59% experienced effective treatment, and 38-57% experienced mycological and clinical cure when assessed 36-48 weeks after completion of 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 completion of terbinafine treatment.

In a study comparing 4 months of continuous (250 mg daily) or intermittent (500 mg daily for 1 week each month) oral terbinafine with intermittent (400 mg daily for 1 week each month) oral itraconazole, a trend favouring continuous terbinafine therapy was observed, but statistically significant differences in cure rates between the regimens were not seen. In a study comparing treatment duration of 6, 12 and 24 weeks in patients with toenail infections, mycological cure rates were substantially higher with the 12- or 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 experienced effective treatment, and 59-90% experienced mycological and clinical cure when assessed 18-42 weeks after completing treatment with oral terbinafine 250 mg daily for 6 weeks. Extending the course of terbinafine to 12 weeks in patients with fingernail infections does not appear to improve response substantially. In one study in patients with fingernail onychomycosis who received oral terbinafine 250 mg daily for 2 or 4 weeks, 65% had mycological and clinical cure 6 months after completion of therapy; 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 receiving terbinafine for the treatment of onychomycosis. Before starting oral terbinafine, patients in Australia 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 advised 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 assessed immediately.

Other uses

In Australia, terbinafine tablets are approved for onychomycosis; use for other fungal infections may be prescribed off-label and should be guided by a healthcare professional. The safety and efficacy of LAMISIL Tablets have not been established in paediatric 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 disturbance has been reported.

Haematological

Pancytopenia has been reported.

Leukocytes

Neutropenia has been reported in patients taking terbinafine.

• A 55-year-old woman who was taking terbinafine and paroxetine presented with fever, diarrhoea and vomiting. A bone marrow biopsy showed overall reduced cellularity, and the aspirate showed a profound shift towards the production of immature myeloid cells, consistent with maturation arrest. Treatment consisted of withdrawal of all outpatient medicines, 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 from hospital without haematological toxicity over 6 months.
• A 60-year-old man presented with fever, oral mucositis, pedal cellulitis and bacteraemia after a 6-week course of terbinafine 250 mg. He was taking concurrent yohimbine for impotence. Bone marrow examination showed a hypocellular marrow with myeloid maturation arrest. Treatment consisted of withdrawal of outpatient medicines, broad-spectrum antibiotics, hydration and G-CSF, and was ultimately successful. Yohimbine was resumed later without any adverse 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 withdrawal of the drug and administration of G-CSF 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 and had completely disappeared 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 maculopapular rashes.

Generalised rashes, fixed drug eruptions, toxic epidermal necrolysis, and erythema multiforme have all been reported in association with terbinafine.

Storage

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