What is fluconazole?
Fluconazole is a triazole medicine used to treat fungal infections. It is effective against a broad spectrum of fungi including:
- Dermatophytes (tinea infections)
- Yeasts such as candida and malassezia.
- Systemic infections such as cryptococcosis and coccidioidomycosis
In New Zealand, fluconazole is available as 50 mg, 150 mg and 200 mg capsules on prescription (Diflucan®). There is also a 2 mg/ml injection for intravenous use. In New Zealand, the Pharmaceutical Schedule subsidy of the capsules requires Specialist recommendation except for single-dose use, which is on general prescription and also available over the counter.
Fluconazole binds to the fungal p450 enzymes and stops the cells making ergosterol, the main component of the cell wall.
Fluconazole is well absorbed orally with or without food. It is widely distributed in body tissues. It takes 22 to 30 hours for half of the medication to be cleared from the bloodstream and may take several days of continuous treatment to reach a steady concentration. The drug is eliminated unchanged in the urine so doses should be reduced if there is kidney disease.
Dose regime for oral fluconazole
For vulvovaginal candidiasis, a single oral dose of fluconazole 150 mg is usually effective. It can be repeated.
Once-weekly fluconazole is often used off-label to treat toenail fungal infections (onychomycosis).
Larger doses (up to 400 mg daily) are required for systemic infections.
Fluconazole is not normally used in children but doses of 5 mg/kg/day have been safely prescribed for a serious infection.
Side effects of fluconazole
Fluconazole is generally well tolerated. Occasional side effects include:
- Nausea and vomiting.
- Diarrhoea and flatulence.
- Abnormal liver function tests (10%); severe hepatitis has been reported very rarely.
- Allergic skin rash including urticaria, exfoliative dermatitis.
- Endocrine effects including enlarged breasts (in males), alopecia and impotence.
Fluconazole should not normally be taken in pregnancy. Use during breast-feeding is acceptable as the drug level found in breast milk is very low.
Drug interactions with fluconazole
Unfortunately, fluconazole can interact with other medications.
- Fluconazole should not be taken with the HMG Co-A reductase inhibitor simvastatin, and the dose of atorvastatin should be reduced. Pravastatin and rosuvastatin are preferable. Toxicity results in muscle pain and weakness, which may be serious.
Fluconazole may increase the concentration of these drugs and enhance their effect:
- Antidiabetic sulphonylurea medication (tolbutamide, glibenclamide, gliclazide, glipizide.
Rifampicin may slightly decrease the concentration of fluconazole.
Fluconazole is not thought to interact with the oral contraceptive pill.
Antifungal drug resistance
In recent years, both topical and oral allylamine and triazole antifungal drug resistance has become a problem, particularly in the Indian subcontinent.
Extensive therapy-resistant dermatophyte infection should prompt this as a possible problem. Where available, fungal culture and estimation of drug minimum inhibitory concentration determined to guide appropriate medication
For more information, see antifungal drug resistance.