Fluconazole

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts.

Triazole antifungal agent.

Inhibits fungal cytochrome P450 synthesis of ergosterol, resulting in decreased cell wall integrity and leakage of essential cellular components.

Susceptible organisms in vivo: Cryptococcus neoformans. Candida krusei is resistant; Torulopsis glabrata is less susceptible.

Routes of Administration: Oral, IV (Same dose for both routes).

Condition: Vaginal candidiasis

Dose: Adults: 150 mg as single oral dose.

Condition: Orpharyngeal or esophageal candidiasis

Dose: Adults: 200 mg, then 100 mg/d for minimum of 14 days.

Children: 6 mg/kg first day, then 3 mg/kg once daily for min¬imum of 14 days.

Condition: Candidal UTI and peritonitis

Dose: Adults: 50-200 mg/d.

Condition: Systemic candidiasis

Dose: Adults Optimal dosage and duration have not been determined although doses up to 400 mg/d have been used.

Children: 6-12 mg/kg/d.

Condition: Cryptococcal meningitis

Dose: Adults 400 mg first day, then 200-100 mg/d for 10-12 weeks after CSF culture is negative.

Children: 12 mg/kg first day, then 6 mg/kg once daily for 10-12 weeks after CSF culture is negative.

Condition: Prevention of relapse of cryptococcal meningitis in AIDS patients

Dose: Adults: 200 mg once daily.

Children: 6 mg/kg once daily.

Condition: Prevention of candidiasis in bone marrow transplant patients

Dose: Adults: 400 mg once daily in patients expected to have severe granulocytopenia <500 neutrophils/mm3. Start fluconazole several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises about 1000 cells/ mm3.

Kidney disease: Creatinine clearance 10-50 mL/min: administer 50% of usual dose.

Liver disease: None.

Elderly: None

Pediatric: See above.

Food: No restrictions.

Pregnancy: Category C.

Lactation: Appears in breast milk. Use with caution.

Contraindications: Hypersensitivity to fluconazole.

> Use with caution in patients with hypersensitivity to other azoles, kidney disease.

> Review drugs that patient is currently taking to avoid possible dangerous drug interactions.

> There have been several reports of fatal exfoliative skin reactions, particularly in patients with serious diseases.

> Fluconazole increases effects/toxicity of following drugs: cyclosporine, glipizide, glyburide, phenytoin, theophylline, tolbutamide, warfarin, zidovudine, cisapride.

> The following drugs decrease effects/toxicity of fluconazole: cimetidine, rifampin.

> Common: nausea, vomiting, diarrhea, abdominal pain, rash.

> Serious: hepatotoxicity (rare), exfoliative skin disorders (rare)

> Signs and symptoms of liver toxicity.

> For AIDS patients: Signs and symptoms of rash which might indicate serious exfoliative skin disorder. Discontinue if lesions do not subside.

> Report symptoms of possible liver dysfunction: jaundice, anorexia, dark urine, pale stools, nausea, vomiting.

> Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known.

> Avoid alcohol.

> To minimize possible photosensitivity reaction, apply adequate sunscreen and use proper covering when exposed to strong sunlight.

> Fluconazole is very well absorbed after oral dosing, even in neutropenic patients, patients with AIDS, and patients on antacids.

> High drug levels achieved in CSF.

> Fluconazole is used in cryptococcal meningitis (usually after initial treatment with amphotericin B± flucytosine x 2 weeks) and coccidiomycosis meningitis.

> Also useful in infections such as esophagitis, mucocutaneous candidiasis, and Candida vaginitis.