fluconazole
DiFlucan

Available forms
Available by prescription only
Injection: 200 mg/100 ml, 400 mg/200 ml
Suspension: 10 mg/ ml, 40 mg/ml
Tablets: 50 mg, 100 mg, 150 mg, 200 mg

Indications and dosages
 Oropharyngeal and esophageal candidiasis. Adults: 200 mg P.O. or I.V. on day 1 followed by 100 mg P.O. or I.V. once daily. As much as 400 mg daily has been used for esophageal disease. Continue for at least 2 weeks after symptoms resolve.
Children: 6 mg/kg on day 1, followed by 3 mg/kg for at least 2 weeks.
 Systemic candidiasis. Adults: Up to 400 mg P.O. or I.V. once daily. Continue for at least 2 weeks after symptoms resolve.
Children: 6 to 12 mg/kg/day I.V. or P.O.
 Cryptococcal meningitis. Adults: 400 mg I.V. or P.O. on day 1, followed by 200 mg once daily. Continue treatment for 10 to 12 weeks after CSF culture becomes negative. For suppression of relapse in patients with AIDS, give 200 mg once daily.
Children: 12 mg/kg I.V. or P.O. on the first day, followed by 6 mg/kg once daily for 10 to 12 weeks.
 Vaginal candidiasis. Adults: 150 mg P.O. as a single dose.
 Urinary tract infection or peritonitis. Adults: 50 to 200 mg P.O. or I.V. daily.
 Prophylaxis in patients undergoing bone marrow transplantation. Adults: 400 mg P.O. or I.V. daily for several days before transplantation and for 7 days after neutrophil count increases to above 1,000 cells/mm³.
 Candidal infection, long-term suppression in patients with HIV infection. Adults: 100 to 200 mg P.O. or I.V. daily.
 Prophylaxis against mucocutaneous candidiasis, cryptococcosis, coccidioidomycosis, or histoplasmosis in patients with HIV infection. ◇ Adults: 200 to 400 mg P.O. or I.V. daily.
Children and infants: 2 to 8 mg/kg P.O. daily.
≡ Dosage adjustment. For patients with renal impairment, adjust dosages as below.

Creatinine clearance (ml/min) Percentage of usual adult dose 21-49 50 11-20 25

Patients receiving hemodialysis should receive one full dose after each session.

Pharmacodynamics
Antifungal action: Fluconazole exerts its fungistatic effects by inhibiting fungal cytochrome P-450. The spectrum of activity includes Cryptococcus neoformans, Candida (including systemic C. albicans) species, Aspergillus flavus, Aspergillus fumigatus, Coccidioides immitis, and Histoplasma capsulatum.

Pharmacokinetics
Absorption: After oral administration, absorption is rapid and complete.
Distribution: Well distributed to various sites, including CNS, saliva, sputum, blister fluid, urine, normal skin, nails, and blister skin. CNS levels of drug approach 50% to 90% of that of serum. Fluconazole is 12% protein-bound.
Metabolism: Fluconazole is primarily metabolized hepatically.
Excretion: Primarily excreted via the kidneys. More than 80% of an administered dose is excreted unchanged in the urine. Excretion rate diminishes as renal function decreases.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and other drugs in same class.

Interactions
Drug-drug. Amitriptyline, carbamazepine, I.V. midazolam: Increases serum levels of these drugs. Monitor patient for increased adverse reactions or toxicity.
Cimetidine: Decreases fluconazole levels. Monitor patient carefully.
Cyclosporine: Increases cyclosporine levels. Monitor cyclosporine levels.
Glipizide, glyburide, sulfonylureas, tolbutamide: Increases hypoglycemic effects. Use together cautiously and monitor blood glucose.
Hydrochlorothiazide: Decreases fluconazole clearance, elevating serum levels. Use together cautiously.
Isoniazid, phenytoin, rifampin, sulfonylureas, valproic acid: Increases hepatic transaminase levels. Monitor patient carefully.
Phenytoin: May significantly increase phenytoin levels. Monitor phenytoin levels.
Rifampin: May decrease fluconazole levels. Monitor patient for drug effects.
Tacrolimus: Increases tacrolimus levels. Monitor patient carefully.
Theophylline: Increases theophylline levels. Monitor theophylline levels.
Warfarin: Enhances hypoprothrombinemic effects. Monitor PT and INR closely.
Zidovudine: Increases zidovine activity. Monitor patient carefully.
Drug-food. Caffeine: May increase caffeine levels. Discourage caffeine use.

Adverse reactions
CNS: headache.
GI: nausea, vomiting, abdominal pain, diarrhea.
Hepatic: hepatotoxicity.
Skin: rash, Stevens-Johnson syndrome, alopecia.
Other: anaphylaxis.

Effects on lab test results
• May increase alkaline phosphatase, ALT, AST, bilirubin, and GGT levels.
• May decrease WBC and platelet counts.

Overdose and treatment
Signs and symptoms of overdose may include hallucinations, paranoid behaviors, decreased motility and respiration, ptosis, urinary incontinence, and cyanosis.
 Treatment is largely supportive and includes gastric lavage, if indicated.

Special considerations
• Fluconazole isn’t compatible with other I.V. drugs.
• Bioavailability of oral drug is comparable to I.V. dosing.
• Adverse reactions (including transaminase elevations) are more frequent and more severe in patients with severe underlying illness (including AIDS and malignancies).
Pregnant patients
• Don’t give fluconazole to pregnant HIV-infected women and discontinue if pregnancy occurs. Use in pregnancy only if potential benefits outweigh risk to fetus.
Breast-feeding patients
• Drug appears in breast milk at levels similar to those of plasma. Therefore, use in breast-feeding women isn’t recommended.
Pediatric patients
• Safety and efficacy in children younger than age 6 months aren’t established.

Patient education
• Warn patient of potential adverse reactions and urge patient to promptly report them if they occur.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use