Superficial mucosal candidiasis, Oropharyngeal candidiasis, Esophageal candidiasis, Cryptococcal meningitis
Fluconazole is a triazole antifungal agent. It is a potent inhibitor of fungal cytochrome P-450 dependent enzymes. Cytochrome P-450 enzyme system is essential component of fungal cell membrane which is responsible for the synthesis of ergosterol.
Adult : PO Superficial mucosal candidiasis 50 mg/day, up to 100 mg/day. Treatment duration: 7-30 days depending on condition. Candidal balanitis; Vag candidiasis 150 mg as a single dose. Cutaneous candidiasis; Dermatophytosis; Pityriasis versicolor 50 mg once daily for up to 6 wk. Cryptococcal infections; Systemic candidiasis Initial: 400 mg, then 200-400 mg once daily. Prevention of relapse after a primary course of treatment for acute cryptococcal meningitis in AIDS patients 100-200 mg/day. Prophylaxis of fungal infections in immunocompromised patients 50-400 mg/day. IV Cryptococcal infections; Systemic candidiasis Initial: 400 mg, then 200-400 mg once daily. Prevention of relapse after a primary course of treatment for acute cryptococcal meningitis in AIDS patients 100-200 mg/day. Prophylaxis of fungal infections in immunocompromised patients 50-400 mg/day. May be taken with or without food.
In an interaction study, fuconazole increased the prothombin time after warfarin administration in healthy males. Though the magnitude of change was small (12%) careful monitoring of prothombin time in patients receiving coumarin type anticoagulants is recommended.
Fluconazole has been shown to prolong the serum half-life of concomitantly administed oral sulphonyl ureas (chlorpropamide, gilbenclamide, glipizide and tolbutamide) in healthy volunteers. Fluconazole and oral sulphonylureas may be co-administered to diabetic patients, but the possibility of a hypoglycemic episode should be borne in mind.
In a kinetic interaction study, co-administration of multiple-dose hydrochlorothiazide to healthy volunteers receiving fuconazole increased plasma concentrations of fuconazole by 40%. An efect of this magnitude should not necessitate a change in the fuconazole dose regimen in subjects recieving concomitant diureties, although the prescribers should bear it in mind.
Concomitant administration of fuconazole and phenytoin may increase the level of phenytoin to a clinically signifcant degree. Administration of fuconazole and rifampicin has resulted in a 25% decrease in the AUC and 20% shorter half-life of fuconazole. Patients recieving concomitant rifampicin, an increase in the fuconazole dose should be considered.
Two kinetic studies with combined oral contraceptive have been performed using muitiple dose of fuconazole. There were no relevant efects on either hormone level in the 50 mg fuconazole study, while at 200 mg daily the AUCs of ethinyl estradiol and levonorgestrel were increased 40% and 4% respectively. Thus multipule dose use of fuconazole at these dose is unlikely to have an efect on the efcacy of the combined oral contraceptives. Fluconazole 50 mg daily does not afect endogenous steroid levels in females. 200-400 mg daily has no clinically singnifcant efect on endogenous steroid levels or on ACTH stimulated response in healthy male volunteers.
A kinetic study in renal transplant patients found fuconazole 200 mg daily to slowly increase cyclosporin concentrations. However, in another multiple dose study with 100 mg daily, fuconazole did not afect cyclosporin levels in patients with bone marrow transplants. Cyclosporin plasma concentration monitoring in patients receiving fuconazole is recommended.
Interaction studies have shown that when oral fuconazole is co-administered with food. cemetidine, antacids or following total body irradiation for bone marrow transplantation, no clinically signifcant impairment of fuconazole absorption occurs.
In placebo-controlled interaction study, the administration of fuconazole 200mg for 14 days resulted in an 18% decrease, in the mean plasma clearance of theophyline, Patients who are receiving dose of theophyline or who are otherwise at increased risk for theophyline toxicity should be observed for sign of toxicity while receiving fuconazole, and the therapy modifed appropriately if sign of toxicity while receiving fuconazole, and the therapy modifed appropriately if sign of toxicity develop.
Physicians should be aware that drug-drug interaction studies with other medications have not been conducted, but that such interactions may occur.
Hypersensitivity. Co-admin w/ terfenadine, cisapride, astemizole, pimozide, quinidine, halofantrine and erythromycin. Patient w/ potentially proarrhythmic conditions. Renal and hepatic impairment. Pregnancy and lactation.
Abdominal pain, diarrhoea, flatulence, nausea, vomiting, taste disturbance, headache, dizziness, leucopenia, thrombocytopenia, hyperlipidaemia, increased liver enzyme values, alopecia, hypokalaemia, Rarely, angioedema, toxic epidermal necrolysis. Potentially Fatal: Hepatotoxicity. Rarely, Stevens-Johnson syndrome, anaphylaxis.
PO: C (For a single dose of 150 mg for vaginal candidiasis), D (for use in indications other than vag candidiasis); Parenteral: D
In the event of overdosage, supportive measures and symptomatic treatment with gastric lavage if necessary may be adequate. As fuconazole is excreted largely in the urine, forced volume diuresis would probably increase the elimination rate. A three hour session of haemodialysis decreases plasma levels by approximately 50%.
Keep in a dry place away from light and heat. Keep out of the reach of children.
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