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INDEX |
| Introduction | Fluconazole is a synthetic compound known as a bis-triazole. It was first used in patients 1994/95 and licensed for use in 1990. It goes off patent in 2003. Current annual sales (1999) exceeds $1 billion. It is manufactured and sold by Pfizer. It works by inhibiting the production of ergosterol, a central chemical in the cell walls of fungi. | |
| Dose & Delivery | The drug is available as a capsule, oral suspension and intravenous infusion. Typical doses for oral thrush are 50-100mg per day, but larger doses are used in AIDS patients. The typical dose for vaginal thrush is a 150mg per day. For the prevention of fungal infections in leukaemia, doses from 50-400mg per day have been used and studied. Most authorities recommend between 100 and 400mg. For the treatment of candidemia and other serious Candida infections a minimum dose of 400mg per day is recommended with increased doses in patients on haemofiltration and/or rifampicin (see below). Some authors have suggested that 800mg is superior for candidaemia and this is presently undergoing clinical trials. For the treatment of cryptococcal meningitis, a minimum of 400mg per day initially is used until the patient is stable and then typically 200mg per day. Much larger doses e.g. 800mg per day have been used for patients failing therapy in cryptococcal meningitis. Larger doses such as 800-1200mg per day have been used for coccidioidal meningitis. Almost all other treatments have been for 100-400mg per day. | |
| Fungi - the drug is active against. |
Fluconazole is active against most Candida
species, with the absolute exception of Candida
krusei and partial exception of Candida
glabrata and a small number of isolates of
Candida albicans, Candida tropicalis, Candida
parapsilosis and other rare species. It is also
active against the vast majority of Cryptococcus
neoformans isolates. It is active against many other
yeasts including Trichosporon beigelii, Rhodotorula
rubra, and the dimorphic endemic fungi including
Blastomyces dermatitidis, Coccidioides immitis,
Histoplasma capsulatum and Paracoccidioides
brasiliensis. It is less active than itraconazole
against these dimorphic fungi. It is not active against
Aspergillus or Mucorales. It is active against
skin fungi such as Trichophyton. Increasing resistance in Candida albicans in patients with AIDS has been reported. Typical rates of resistance, in Candida albicans in a general hospital are 3-6%, in Candida albicans in AIDS 10-15%, in Candida krusei 100%, in Candida glabrata ~50-70%, in Candida tropicalis 10-30% and in other Candida species less than 5%. |
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| Metabolism distribution and excretion. | Fluconazole is water soluble, well absorbed after oral administration and serum concentration parallels dose. Babies and children, especially those with fevers, have accelerated metabolism. Most of the drug is excreted in the urine; very little is metabolised by the liver. The drug penetrates well into cavities such as around the brain, the eyes, saliva and urine. | |
| Drug/ Drug interactions | There are very few drug/drug interactions with fluconazole. The most profound is with rifampin (rifampicin) and phenytoin which accelerate the metabolism of fluconazole in liver and reduce serum levels. In addition fluconazole can cause a rise in serum levels of phenytoin and diabetic drugs, such as chlorpropamide, glibenclamide, glipizide and tolbutamide and warfarin. It also increases cyclosporin levels slightly. | |
| Side effects | Fluconazole is generally well tolerated, and is probably the least toxic of all the antifungal drugs. Its common side effects are nausea and abdominal discomfort; raised liver function tests occasionally occur. Skin rashes occur in up to 1 in 20 patients and these may be severe in rare cases. There are no endocrine effects of fluconazole. | |
| Other information |