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FLUTROX (Fluconazole USP)

FLUTROX (Fluconazole) is the first of a new class of synthetic broad spectrum bis-triazole antifungal agents. It is active against a broad spectrum of fungal pathogens and acts by inhibition of the ergosterol component of the fungal cell membrane.

Chemically Fluconazole is designated as 2,4-Difluoro-α,α-bis (1H-1,2,3,4-TRIAZOL-1-ylmethyl)benzyl alcohol.

Mode of action

FLUTROX (Fluconazole) is a highly selective inhibitor of fungal sterol synthesis without effect on mammalian or human steroid synthesis. It acts by inhibiting the synthesis of ergosterol, a major component of the cell membrane of yeast and fungi. Specifically, the nitrogen in the azole ring is thought to bind to lanosterol-14-α-demethylase, a fungal cytochrome P450 enzyme & thereby inhibits the conversion of lanosterol to ergosterol. Inhibition of ergosterol synthesis i s thought to lead to the accumulation of non-functional sterols and to the disruption of normal membrane functions including the co-ordination of chitin synthesis, the activity of membrane-bound sterols, and the preservation of normal permeability.

Spectrum of activity

FLUTROX (Fluconazole) is effective against many fungi including yeasts and dermatophytes. Fluconazole does not appear to have any antibacterial activity. In vivo, FLUTROX (Fluconazole) is effective against strains of Candida, Cryptococcus neoformans, Blastomyces dermatidis, Histoplasma capsulatum and Coccidiodes immitis.

Indications

Vaginal candidiasis
Mucosal candidiasis, e.g. oropharyngeal, oesophageal, mucocutaneous and chronic oral atropic candidiasis, etc.
Systemic candidiasis: candidaemia, disseminated candidiasis, infection of peritoneum, respiratory and urinary tract.
Cryptococcosis: cryptococcal meningitis, primary as well as maintenance therapy.
Prevention of fungal infection in patients with malignancy, AIDs, in intensive care units and in patients on immunosuppressive drugs.
Fungal infections of the skin and nails.

Dosage and administration

FLUTROX (Fluconazole) is used as once daily dose for the following indications

Vaginal candidiasis: 150mg single oral dose
Oropharyngeal candidiasis: 50mg once daily for 7 to 14 days.
Systemic candidiasis: 200mg daily for 28 days
Oesophageal candidiasis (acute): 50-100mg for 21 days
Cryptococcal meningitis (acute): 200mg daily for 10-12 weeks after CSF becomes culture negative
Tinea corporis: 150mg once a week up to 4 weeks
Tinea cruris: 150mg once a week up to 4 weeks
Tinea pedis: 150mg once a week up to 4 weeks
Cutaneous candidiasis: 150 once a week up to 4 weeks
Onychomycosis: 150 mg once a week 6-12 months
Atrophic oral candidiasis associated with dentures: 50mg once daily for 14 days.
For other candidal infections 50mg daily for 14 to 30 days.

Contraindications

Hypersensitivity to Fluconazole or related azole compounds

Warnings and precautions

Patients who develop abnormal liver function should be monitored.
Immunocompromised patients who develop rash during Fluconazole therapy should be monitored and the drug discontinued if lesion progresses.

Use in pregnancy, nursing mothers and children

There are no adequate and well controlled studies in pregnant women. FLUTROX should be used in pregnancy only if the benefits outweigh the risks. Since it is secreted in human milk, it should not be used in lactating women.

FLUTROX is not recommended for children below 16 years as limited data is available. A small number of patients from age 3 to 13 years have been treated safely with Fluconazole using doses of 3-6mg/kg daily.

Drug interactions

Fluconazole has shown to prolong prothrombin time of coumarin drugs hence requires careful monitoring.
Concomitant administration of Fluconazole and cyclosporine may result in an increase in cyclosporine levels.
Fluconazole significantly increase phenytoin levels and AUC resulting in phenytoin toxicity.
Concomitant administration of Fluconazole and oral hypoglycemic such as sulphonylurea in diabetic patients results in increased plasma concentration and reduced metabolism of anti-diabetic agents.
Concomitant administration of Fluconazole and rifampicin decreases AUC for Fluconazole by 20%

Side effects

Fluconazole is generally well tolerated. Commonly reported side effects are nausea, vomiting, abdominal pain, headache, skin rash and diarrhea. Mild transient, reversibleincrease in liver enzymes like ALT, AST, alkaline phosphatase and serum bilirubin, etc. may be seen. Serious hepatotoxicity is rarely seen. Clinical adverse reactions have been more frequently reported in HIV patients than in non-HIV infected patients, however, the patterns were similar. In rare cases anaphylaxis has been reported.

Overdosage

In the event of overdosage, supportive measures and symptomatic treatment with gastric lavage if necessary, may be adequate. As fluconazole is excreted largely in urine, forced dieresis would probably increase the elimination rate. A three hour session of haemodialysis decreases plasma levels by approximately 50%

FLUTROX (Fluconazole USP)

FLUTROX (Fluconazole USP)