Synthetic broad-spectrum bistriazole antifungal agent.
Pharmacology: Fluconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14α-demethylation. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. The subsequent loss of normal sterols correlates with the accumulation of 14α-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole.
Microbiology: Fluconazole is active against Blastomyces dermatitidis, Candida sp, Coccidioides immitis, Cryptococcus neoformans, Epidermophyton sp, Histoplasma capsulatum, Microsporum and Trichophyton spp. Resistance has developed in some Candida sp. Ketoconazole-resistant strains of C. albicans have been found to be cross-resistant to fluconazole.
Pharmacokinetics: Fluconazole is almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are 4-8 mcg/mL after repetitive doses of 100 mg. Renal excretion accounts for >90% of elimination and the elimination half-life is 25 hrs. Fluconazole diffuses readily into body fluids, including sputum and saliva; concentrations in CSF are 50-90% of the simultaneous values in plasma.
Oropharyngeal and esophageal candidiasis; vaginal and mucosal candidiasis; cryptococcal and fungal meningitis; fungal infections in patients with malignancy.
Oropharyngeal or Oesophageal Candidiasis: 200 mg on the 1st day then 100 mg once daily. Maximum Dose: 400 mg/day.
Deep-Seated Candidiasis: 400 mg on 1st day then 200 mg once daily for 4 weeks and for at least 2 weeks after resolution of symptoms.
Cryptococcal Meningitis: 400 mg on 1st day then 200 mg once daily. Maximum Dose: 400 mg/day for 10-12 weeks, thereafter, 200 mg once daily.
Vaginal Candidiasis: 150 mg oral dose once daily.
Neutropenic Cancer: 50-100 mg daily.
There has been a reported case of overdosage with fluconazole. In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted. Fluconazole is largely excreted in urine. A 3-hr hemodialysis session decreases plasma levels by approximately 50%.
Hypersensitivity to fluconazole.
Use in pregnancy & lactation: Fluconazole is not recommended in pregnancy and breastfeeding women.
Fluconazole should be used with caution in patients with impaired renal or hepatic function.
Fluconazole is not recommended in pregnancy and breastfeeding women.
Nausea, abdominal discomfort, diarrhoea, flatulence and occasional abnormalities of liver enzymes; rarely, rash (discontinue treatment or monitor closely if infection is invasive or systemic); angioedema, anaphylaxis, bullous lesions and Stevens-Johnson syndrome have been reported; severe cutaneous reactions in AIDS patients have also been reported.
Concomitant administration of the enzyme-inducing agent rifampicin with fluconazole result in reduced serum concentrations of fluconazole. Administration of hydrochlorothiazide and fluconazole has resulted in clinically insignificant increases in serum-fluconazole concentrations.
Fluconazole may interfere with the metabolism of some drugs if given concomitantly. This may account for the reported increases in plasma concentrations of phenytoin, sulfonylurea, hypoglycaemic agents, cyclosporin, nortriptyline and zidovudine. Increases in terfenadine concentrations following high doses of fluconazole have been associated with ECG abnormalities. Fluconazole may also increase the effect of some oral anticoagulants and reduce the clearance of theophylline.
J02AC01 - fluconazole ; Belongs to the class of triazole derivatives. Used in the systemic treatment of mycotic infections.