Funzole®
Fluconazole

COMPOSITION:
Funzole® 50mg Capsule: Each capsule contains Fluconazole USP 50mg.
Funzole® Oral suspension: Each 5ml contains Fluconazole USP 50mg.

PHARMACOLOGICAL INFORMATION:
Pharmacological Action
Fluconazole (USP) is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. Fluconazole is active against the following microorganisms: Blastomyces dermatitidis, Candida spp. (except C. krusei and C. glabrata) Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp., Histoplasma capsulatum, Microsporum spp. Trichophyton spp. Following oral dosing, fluconazole is almost completely absorbed within two hours. Bioavailability is not significantly affected by concomitant intake of meals or the use of H2-antagonists (eg. ranitidine). The elimination half-life of fluconazole follows zero order kinetics and only 10% of elemination is due to metabolisim, the remainder is excreted in urine and sweat.

Mechanism of Action
Like other imidazole and triazole-class antifungals, fluconazole inhibits the fungal cytochrome P450 enzyme 14a-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cell wall, and subsequent accumulation of 14a-methyl sterols. Fluconazole is primarily fungistatic, however may be fungicidal against certain organisms in a dose-dependent manner.

CLINICAL INFORMATION:
Therapeutic Indications
Funzole® is indicated for the treatment and prophylaxis of fungal infections where other antifungals have failed or are not tolerated (eg. due to adverse effects), including: Candidiasis caused by susceptible strains of Candida, Tinea corporis, tinea cruris or tinea pedis, Onychomycosis, Cryptococcal meningitis.

Fluconazole can be used first-line for the following indications: Coccidioidomycosis, Cryptococcosis, Histoplasmosis, Prophylaxis of candidiasis in immunocompromised people.

Dosage and Administration
Acute or recurrent vaginal candidiasis - a single dose of 150mg . Mucosal candidiasis (except vagina) : 50mg daily (100mg daily in unusually difficult infection) given for 7-14 days in other mucosal infections (e.g Oesophagitis, candiduria ). Systemic candidiasis and cryptococcal infections(including meningitis )- 400mg initially then 200mg daily . Increased if necessary to 400mg daily , treatment continued according to response.

Child over 1 year - superficial candidal infections , 1-2 mg/kg body weight daily , systemic candidiasis and cryptococcal infections , 3-6 mg/kg body weight daily (in serious life threatening infections upto 2 mg/kg body weight daily has been given to children aged 4-13 years-max. 400 mg daily).

Contraindication
Fluconazole is contraindicated in patients with known hypersensitivity to fluconazole or other azole antifungals, concomitant use of cisapride, due to risk of serious cardiac arrhythmias.

Precautions
Fluconazole therapy has been associated with QT interval prolongation, which may lead to serious cardiac arrhythmias. Thus it is used with caution in patients with risk factors for prolonged QT interval such as electrolyte imbalance or use of other drugs which may prolong the QT interval (particularly cisapride).

Fluconazole has also rarely been associated with severe or lethal hepatotoxicity and liver function tests are usually performed regularly during fluconazole therapy. Additionally, it is used with caution in patients with pre-existing liver disease.

High concentrations of fluconazole have been detected in human breast milk from patients receiving fluconazole therapy, thus its use is not recommended in breastfeeding mothers.

Adverse effects
Adverse drug reactions associated with fluconazole therapy include: Common (>1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhoea, and/or elevated liver enzymes, Infrequent (0.1-1% of patients): anorexia, fatigue, constipation. Rare (<0.1% of patients): oliguria, hypokalaemia, dizziness, paraesthesia, seizures, alopecia, Stevens-Johnson syndrome, thrombocytopaenia, other blood dyscrasias, serious hepatotoxicity including hepatic failure, anaphylactic/anaphylactoid reactions.

Drug interactions
Fluconazole is an inhibitor of the human cytochrome P450 system, particularly the isozymes CYP2C9 and CYP3A4. Fluconazole may decreases the metabolism and increases the concentration of any drug metabolised by these enzymes. Additionally, its potential effect on QT interval increases the risk of cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval.

PHARMACEUTICAL INFORMATION:
Storage Conditions
Store in a cool (below 30ºC) and dry place, away from light. Keep out of reach of children

Presentation & Packaging
Funzole® 50mg Capsule: Each commercial box contains 3x10's capsules in Alu-PVC blister pack.
Funzole® Oral suspension: Each box contains dry poweder for preparation of 35ml suspension with a mesaring cup.