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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 coccidiodomycosis

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, Pharmaceutical Schedule subsidy of the capsules requires Specialist recommendation.

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 blood stream 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.

For dermatophyte (tinea) infections and pityriasis versicolor, either 50 mg daily or 150 mg once weekly is taken for two to six weeks.

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 serious infection.

Side effects of fluconazole

Fluconazole is generally well tolerated. Occasional side effects include:

  • Nausea and vomiting.
  • Diarrhoea and flatulence.
  • Headache.
  • 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 not generally recommended, because the drug is found in breast milk.

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:

  • Warfarin
  • Antidiabetic sulphonylurea medication (tolbutamide, glibenclamide, gliclazide, glipizide.
  • Phenytoin
  • Theophylline
  • Ciclosporin
  • Celecoxib

Rifampicin may slightly decrease the concentration of fluconazole.

Fluconazole is not thought to interact with the oral contraceptive pill.

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