Fluconazole

Indications

Oral
Superficial mucosal candidiasis
Adult: (Except genital candidiasis) Usual dose: 50 mg daily, may increase to 100 mg daily if needed. Recommended treatment duration: 7-14 days (oropharyngeal candidiasis, except in severely immunocompromised patients), 14 days (atrophic oral candidiasis associated with dentures), 14-30 days (other mucosal candidiasis including oesophagitis).
Child: >4 wk: Loading dose: 6 mg/kg followed by 3 mg/kg daily.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Oral
Vaginal candidiasis
Adult: 150 mg as a single dose.
Oral
Candidal balanitis
Adult: 150 mg as a single dose.
Oral
Dermatophytosis
Adult: 50 mg daily for up to 6 wk.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Oral
Pityriasis versicolor
Adult: 50 mg daily for up to 6 wk.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Oral
Cutaneous candidiasis
Adult: 50 mg daily for up to 6 wk.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Oral
Systemic candidiasis
Adult: Initially, 400 mg followed by 200-400 mg daily. Max: 800 mg daily in severe infections. Treatment duration is based on clinical and mycological response but is usually at least 6-8 wk in cryptococcal meningitis. May also be given via IV infusion. To prevent relapse after a primary course of treatment for acute cryptococcal meningitis in AIDS patients: 100-200 mg daily, may also be given via IV admin.
Child: >4 wk: 6-12 mg/kg daily; same doses may given every 72 hr in neonates up to 2 wk and every 48 hr in neonates 2-4 wk. Max: 400 mg daily.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Oral
Cryptococcal infections
Adult: Initially, 400 mg followed by 200-400 mg daily. Max: 800 mg daily in severe infections. Treatment duration is based on clinical and mycological response but is usually at least 6-8 wk in cryptococcal meningitis. May also be given via IV infusion. To prevent relapse after a primary course of treatment for acute cryptococcal meningitis in AIDS patients: 100-200 mg daily, may also be given via IV admin.
Child: >4 wk: 6-12 mg/kg daily; same doses may given every 72 hr in neonates up to 2 wk and every 48 hr in neonates 2-4 wk. Max: 400 mg daily.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Oral
Prophylaxis of fungal infections in immunocompromised patients
Adult: 50-400 mg daily. May also be given via IV infusion.
Child: 3-12 mg/kg daily; may also be given via IV infusion. For infants <2 wk, doses should be given every 72 hr; 2-4 wk, doses should be given every 48 hr. Max: 400 mg daily, or 12 mg/kg at recommended intervals in infants.
Renal impairment: Normal initial doses; adjust subsequent doses based on CrCl. Patients on dialysis: Single recommended dose after each session.

CrCl (ml/min)	Dosage Recommendation
<50 and not receiving dialysis	Maintenance dose: 50% of the recommended doses.

Special Populations: Renal impairment: Initially, administer normal loading or initial doses followed by maintenance doses based on creatinine clearance. CrCl: >50 mL/min: ½ of the standard dose. Patients on regular haemodialysis should be given a standard dose of fluconazole every dialysis session.

Contraindications

Hypersensitivity.

Warnings / Precautions

Renal or hepatic impairment. May prolong QT interval. Pregnancy, lactation.

Adverse Reactions

Nausea, abdominal pain, vomiting, diarrhoea, flatulence; elevated liver function values; headache; rash, exfoliative dermatitis. Rarely, angioedema, anaphylactic reactions and thrombocytopenia.
Potentially Fatal: Hepatotoxicity; rarely anaphylaxis; Stevens-Johnson syndrome.

Overdose Reactions

Treatment is symptomatic and supportive, gastric lavage may be used if needed.

Drug Interactions

Rifampicin reduces fluconazole levels. Reduces theophylline clearance. Affects efficacy of oral contraceptives. May increase serum levels of alprazolam, triazolam, midazolam, diazepam. May raise serum concentrations and efficacy of oral sulphonylureas, phenytoin, ciclosporin, calcium channel blockers, tacrolimus, HMG-CoA reductase inhibitors (except pravastain and fluvastatin), warfarin and other anticoagulants. May reduce metabolism of caffeine. Avoid concurrent use with clopidogrel.
Potentially Fatal: Increased risk of cardiac arrhythmias with astemizole, cisapiride or terfenadine.
See Below for More fluconazole Drug Interactions

Mechanism of Actions

Fluconazole decreases ergosterol synthesis by interfering with cytochrome P450 activity, thus inhibiting cell membrane formation of susceptible fungi including B dermatitidis, Candida spp, C immitis, C neoformans, Epidermophyton spp, H capsulatum, Mycosporum spp, Trichophyton spp, thus leading to cell death.
Absorption: Well absorbed after oral admin; peak plasma concentrations after 1-2 hr (oral), may be increased with multiple dosing.
Distribution: Widely distributed. Protein-binding: 12%.
Excretion: Via urine (80% as unchanged, 11% as metabolites); 30 hr (elimination half-life); increased in renal impairment. Removed by dialysis.

Administration

May be taken with or without food.

Storage Conditions

Oral: Store below 30°C.

ATC Classification

D01AC15 - fluconazole ; Belongs to the class of imidazole and triazole derivatives. Used in the topical treatment of fungal infection.
J02AC01 - fluconazole ; Belongs to the class of triazole derivatives. Used in the systemic treatment of mycotic infections.