Oral antifungal drugs
- Prescribe oral antifungal agents appropriately and safely
Oral antifungal drugs currently in use include itraconazole, fluconazole, ketoconazole and terbinafine. They are reserved for extensive or severe infection for which topical antifungal agents are inappropriate or ineffective, because of high cost, potential side effects and drug interactions. Griseofulvin is not discussed as it is no longer available in New Zealand. Nor is nystatin, as it is only appropriate for intestinal candidiasis. Voriconazole has recently become available but is reserve for the treatment of serious and refractory fungal infections in hospitalised patients.
Oral itraconazole (Sporanox™) is a very useful broad spectrum antifungal drug. It should be taken after a fatty meal, preferably with an acidic drink such as orange juice.
Dosing regimes depend on the skin condition, its duration and severity, and need for prophylaxis. For example:
- Skin infections: 200 mg daily for one to four weeks
- Vulvovaginal candidiasis: 200 mg twice daily for one day OR 200 mg daily for 3 days, repeated if necessary or regularly once-weekly to once-monthly
- Oral candidiasis: 100 mg daily for two weeks
- Onychomycosis: 200 mg/day for 6-8 weeks (fingernails) or 3-4 months (toenails), OR 200 mg twice daily for 7 days, repeated monthly for 2 months (fingernails) or 3-4 months (toenails)
Nausea is the most common side effect. Abnormal liver function tests affect 5% of those on long term therapy but are rarely severe (monitoring is recommended for prolonged courses). It has been reported to cause congestive cardiac failure and serious rashes. The main concern with azoles is serious interactions with other medications.
As itraconazole needs acid for its absorption, antacids, H2 antagonists and omeprazole should not be taken for 2 hours after itraconazole.
These drugs should not be taken by those on itraconazole:
- HMG Co-A reductase inhibitors (atorvastatin, lovastatin, simvastatin) – the interaction may cause heart failure; fluvastatin and pravastatin are acceptable alternatives.
- Midazolam, triazolam
- The antihistamines astemizole and terfenadine (withdrawn from New Zealand market)
The dose of these drugs should be reduced:
- Methyl prednisolone
- Vinca alkaloids
The dose of these drugs may need reducing if side effects arise:
- Calcium channel blockers
- Antidiabetic sulphonylureas
The following drugs decrease the concentration of itraconazole:
Itraconazole is not thought to interact with the oral contraceptive pill and must be avoided in pregnancy.
Fluconazole (Diflucan™) is a triazole used for candidiasis and cutaneous dermatophyte infections. It is not registered for nail infections. The dose and duration depends on the nature and severity of infection. Typically:
- Oropharyngeal candidiasis: 50mg daily for 7-14 days
- Vaginal candidiasis: 150 mg single dose
- Dermatomycoses: 150 mg once weekly for 2 to 6 weeks
The main contraindication is concomitant administration with cisapride. It should be avoided in pregnancy / lactation and in the presence of electrolyte abnormalities, heart disease and renal impairment.
Side effects include:
- GI disturbance
- Rashes including urticaria, exfoliative dermatitis
Drug interactions are similar to those for itraconazole. Refer to a current prescribing text.
Ketoconazole (Nizoral™) is used to treat fungal infections where other treatments have failed or are contraindicated. It is effective for yeasts and dermatophytes and is usually prescribed in a daily dose of 200mg after food.
Its main concern is hepatic – liver function should be monitored. The incidence of significant hepatitis is about 1:1500, much higher than with itraconazole. It has similar interactions with other drugs.
Terbinafine can be taken with or without food. Listed side effects include:
- GI upset
- Rashes including urticaria, toxic epidermal necrolysis
- Arthralgia and myalgia
- Taste disturbance
- Hepatobiliary dysfunction
Drug interactions are not as frequent or as serious as with itraconazole. However, interactions are reported with tricyclic antidepressants, beta-blockers, SSRIa, MAOIs, hepatic enzyme inhibitors (cimetidine) or inducers (rifampicin) and possibly with oral contraceptives.
- Pre-treatment and follow-up visits to GP
- Skin scrapings or nail clippings (single sample)
- Topical therapy for 12 months
- Oral therapy for 3 months
- Monitoring blood count and liver function on two occasions
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