Uses and Administration
Terbinafine is an allylamine antifungal given by mouth as the hydrochloride in the treatment of dermatophyte infections of the skin and nails. Oral doses are stated in terms of the base. Terbinafine hydrochloride 1.13 g is equivalent to about 1 g of terbinafine. It is also applied, as the hydrochloride, to the skin in dermatophytoses, in pityriasis versicolor, and in cutaneous candidiasis.
A dose of 250 mg is given once daily by mouth for 2 to 4 weeks for tinea cruris; treatment may be continued for up to 6 weeks for tinea pedis infections; a 4-week course is used in tinea corporis infections. A cream or solution containing 1% terbinafine hydrochloride is applied once or twice daily for 1 to 2 weeks to treat tinea corporis and tinea cruris; a 1-week course is recommended for tinea pedis. A 2-week course of treatment is used in cutaneous candidiasis and pityriasis versicolor.
Dermatophyte infections of the nails are treated with the equivalent of terbinafine 250 mg by mouth once daily for 6 to 12 weeks although longer treatment may be necessary in toe-nail infections.
Dosage should be reduced in patients with renal impairment
Administration in children.
The BNFC suggests the following oral doses for the treatment of tinea capitis in children over 1 year of age:
in those weighing 10 to 20 kg: the equivalent of terbinafine 62.5 mg once daily
in those weighing 20 to 40 kg: 125 mg once daily
in those weighing over 40 kg: 250 mg once daily Treatment is usually given for 2 weeks for tinea capitis, 2 to 4 weeks for tinea cruris, 4 weeks for tinea corporis, and may be continued for up to 6 weeks in tinea pedis. Infections of the nails are treated for 6 to 12 weeks although longer treatment may be required for toe-nail infections.
Similar regimens have been reported in the literature.1,2 A review on the use of terbinafine in children considered it both safe and effective in the management of tinea capitis and onychomycosis.3
The most frequent adverse effects after oral use of terbinafine hydrochloride are gastrointestinal disturbances such as nausea, diarrhoea, and mild abdominal pain. Loss or disturbance of taste may occur and occasionally may be severe enough to lead to anorexia and weight loss. Other frequent adverse effects include headache and skin reactions, including rash or urticaria, sometimes with arthralgia or myalgia. Severe skin reactions including angioedema, photosensitivity, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred rarely. Liver dysfunction with isolated reports of cholestasis, hepatitis, and jaundice, has occurred and there have also been rare cases of hepatic failure, sometimes leading to death or necessitating liver transplantation, in patients both with and without pre-existing liver disease. Other rare adverse effects include paraesthesia, hypoaesthesia, dizziness, malaise, fatigue, and alopecia. Haematological disorders including neutropenia, thrombocytopenia, and agranulocytosis, psychiatric disturbances such as depression and anxiety, and precipitation or exacerbation of cutaneous and systemic lupus erythematosus have been reported very rarely. There may be local reactions after topical use of terbinafine.
Effects on the blood.
Up to October 2004, the Australian Adverse Drug Reactions Advisory Committee had received 14 reports of blood dyscrasias attributed to oral terbinafine including agranulocytosis (7 reports), neutropenia (5reports), and pancytopenia (2reports).1 The reactions generally occurred within 4 to 10 weeks of starting therapy. Nine patients recovered, 4 within one week of stopping treatment. However, a 79-year-old patient who developed agranulocytosis about 2 months after initiation of terbinafine died from septic shock.
Effects on the eyes.
The US manufacturer has noted that changes in the lens and retina of the eye have sometimes been associated with oral terbinafine, although the significance of these changes is not known.
Effects on the salivary glands.
Bilateral parotid swelling was associated with terbinafine in a 38-year-old man.1 Information from the manufacturer and the UK CSM indicated that this effect had occurred in other patients but was very rare. More recently, severe sialadenitis as a complication of drug reaction with eosinophilia and systemic complications (DRESS¬óa type of hypersensitivity reaction) was reported in an 80-year-old woman treated with terbinafine.2 She also had severe xerostomia, lachrymal gland swelling, dry eyes, and keratitis.
Effects on the skin.
Serious skin reactions are occasionally reported in patients receiving terbinafine and have included erythema multiforme, erythroderma, severe urticaria, pityriasis rosea, worsening of pre-existing psoriasis, bullous pemphigoid, acute generalised exanthematous pustulosis, and lupus erythematosus. Several of these patients had a history of auto-immune disease and it has been suggested that this could be a risk factor for developing severe reactions.
Effects on taste.
Disturbance and loss of taste have been reported in about 0.6% of patients receiving terbinafine. While this usually resolves gradually once the drug is withdrawn, persistent impairment of taste has been reported.
Terbinafine should not be used in patients with existing liver disease and liver function tests should be performed in all patients before starting oral therapy. Terbinafine should be discontinued if clinical or biochemical evidence of hepatotoxicity develops. It should also be discontinued if any progressive skin rash occurs and should be used with caution in patients with psoriasis.
Terbinafine should be given in reduced doses to patients with renal impairment
Terbinafine is excreted in breast milk and the manufacturers state that it should be avoided during breast feeding.
Plasma concentrations of terbinafine may be increased by drugs that inhibit its metabolism by cytochrome P450, such as cimetidine, and decreased by drugs that induce cytochrome P450 enzymes, such as rifampicin. Menstrual disturbances including breakthrough bleeding have been reported in patients taking oral contraceptives and terbinafine.
Terbinafine has been shown in vitro to inhibit metabolism mediated by the cytochrome P450 isoenzyme CYP2D6. Hence it may affect the plasma concentrations of drugs predominantly metabolised by this enzyme such as tricyclic antidepressants, beta blockers, SSRIs, and type B MAOIs.
Terbinafine is an allylamine derivative reported to have a broad spectrum of antifungal activity. It is considered to act through inhibition of fungal sterol synthesis. Terbinafine is fungicidal against dermatophytes, moulds, and certain dimorphic fungi and some yeasts.
Additive and synergistic activity was reported with terbinafine in combination with fluconazole or itraconazole against strains of Candida albicans that had reduced susceptibility to azoles in vitro. Terbinafine was also reported to enhance the activity of azoles against Scedosporium prolificans2 and against the protozoan Leishmania braziliensis.
Terbinafine hydrochloride is well absorbed from the gastrointestinal tract. The bioavailability is about 40% because of first-pass hepatic metabolism. Mean peak plasma concentrations of about 1 microgram/mL occur within 2 hours of a single oral dose of 250 mg. Steady state concentrations are about 25% higher than those seen after a single dose and are reached in 10 to 14 days. Terbinafine is extensively bound to plasma proteins. Terbinafine is distributed into the stratum corneum of the skin, the nail plate, and hair where it reaches concentrations considerably higher than those found in plasma. It appears in breast milk.
Terbinafine is metabolised in the liver to inactive metabolites which are excreted mainly in the urine. A plasma elimination half-life varying from 17 to 36 hours has been reported and a terminal elimination half-life of up to 400 hours in patients receiving prolonged therapy, probably representing elimination from skin and adipose tissue. Fungicidal concentrations in nails are maintained for several weeks after therapy is discontinued. The elimination rate may be altered in patients with liver or kidney disease. Less than 5% of a topical dose of terbinafine hydrochloride is absorbed.
Administration in renal impairment.
The UK manufacturer recommends that in patients with renal impairment (creatinine clearance less than 50 mL/minute or serum creatinine greater than 300 micromol/litre) usual oral doses should be halved to the equivalent of 125 mg of terbinafine daily.
An inadvertent beneficial response has been reported1 in an HIV-positive patient with cutaneous leishmaniasis ( ) who was receiving terbinafine 250 mg daily for tinea corporis and onychomycosis. Beneficial results were also reported in a pilot study2 in which patients with cutaneous leishmaniasis received either terbinafine 125 mg twice daily (those aged 5 to 15 years), or terbinafine 250 mg twice daily (those over 15 years), for 4 weeks.
Non-dermatophyte fungal infections.
Beneficial responses to oral terbinafine have been reported in candidal infections of the nails and mouth,1-3 aspergillosis, chromoblastomycosis, paracoccidioidomycosis, and sporotrichosis.3
Terbinafine has been tried in the treatment of seborrhoeic dermatitis. In one study, 60 patients were randomised to receive oral terbinafine 250 mg daily or a placebo cream applied twice daily for 4 weeks.1 Clinical improvement, maintained 8 weeks after completing treatment, in the terbinafine group led the investigators to conclude that oral terbinafine is an effective treatment for seborrhoeic dermatitis, and to suggest that this might be due to its activity against Malassezia ovalis (Pityrosporum ovale) as well as to some anti-inflammatory action. However, the methodology of this study has been questioned2 and further investigation is needed. A further, uncontrolled, study3 of 661 patients who received oral terbinafine 250 mg daily for 12 days each month for 3 months concluded that intermittent oral terbinafine could be effective for seborrhoeic dermatitis, at least in severe or recalcitrant forms.
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Martindale: The Complete Drug Reference ¬© 2007 The Pharmaceutical Press.
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