Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the TOKU-Es product data sheet. According to the United States Centers for Disease Control, fluconazole resistance among Candida strains in the U.S. is about 7%. Contraindications
Fluconazole is contraindicated in patients who:
Drink alcohol
have known hypersensitivity to other azole medicines such as ketoconazole;
are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;
concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages;
take SSRIs such as fluoxetine or sertraline. Side effects
Adverse drug reactions associated with fluconazole therapy include:
Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes
Infrequent (0.1–1% of patients): anorexia, fatigue, constipation
Rare (<0.1% of patients): oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions
Very rare: prolonged QT interval, torsades de pointes
FDA is now saying treatment with chronic, high doses of fluconazole during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants.If taken during pregnancy it may result in harm.
This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α-methyl sterols. Fluconazole is primarily fungistatic; however, it may be fungicidal against certain organisms in a dose-dependent manner, specifically Cryptococcus. Pharmacokinetics
Following oral dosing, fluconazole is almost completely absorbed within two hours. Bioavailability is not significantly affected by the absence of stomach acid. Concentrations measured in the urine, tears, and skin are approximately 10 times the plasma concentration, whereas saliva, sputum, and vaginal fluid concentrations are approximately equal to the plasma concentration, following a standard dose range of between 100 mg and 400 mg per day. The elimination half-life of fluconazole follows zero order, and only 10% of elimination is due to metabolism, the remainder being excreted in urine and sweat. Patients with impaired renal function will be at risk of overdose.In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. History
Fluconazole was patented by Pfizer in 1981 in the United Kingdom and came into commercial use in 1988. Patent expirations occurred in 2004 and 2005. References
External links
"Fluconazole". Drug Information Portal. U.S. National Library of Medicine. Doi : Evolution of Fluconazole-Resistant Candida albicans Strains by Drug-Induced Mating Competence and Parasexual Recombination