FLUZOLE

What it is

FLUZOLE is a hard gelatin capsule containing fluconazole as the active ingredient, available in strengths of 50 mg, 100 mg and 200 mg. Fluconazole is a white to off-white crystalline powder which is sparingly soluble in water and saline. The capsules contain lactose monohydrate, sulfites and phenylalanine as excipients with known effect.

Approved indications

— Treatment of cryptococcal meningitis in patients who are unable to tolerate amphotericin B. — Maintenance therapy to prevent relapse of cryptococcal meningitis in patients with acquired immune deficiency syndrome (AIDS). — Treatment of oropharyngeal and oesophageal candidiasis in AIDS and other immunosuppressed patients. — Secondary prophylaxis of oropharyngeal candidiasis in patients with human immunodeficiency virus (HIV) infection. — Serious and life-threatening Candida infections in patients who are unable to tolerate amphotericin B. — Vaginal candidiasis, when topical therapy has failed. — Treatment of extensive tinea corporis, extensive tinea cruris and extensive tinea pedis infections in immunocompetent patients in whom topical therapy is not a practical treatment option.

Dosing overview

The daily dose should be based on the infecting organism and the patient's response to therapy, and treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided.

Key safety warnings

Anaphylaxis has been reported in rare instances. Patients have rarely developed exfoliative cutaneous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis during treatment with fluconazole, and drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported. AIDS patients are more prone to the development of serious cutaneous reactions to many drugs, and if a rash attributable to fluconazole develops in a patient treated for a superficial fungal infection, fluconazole should be discontinued. Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram, with fluconazole causing QT prolongation via the inhibition of rectifier potassium channel current (Ikr). During post-marketing surveillance, there have been very rare cases of QT prolongation and torsade de pointes in patients taking fluconazole, including seriously ill patients with multiple confounding risk factors such as structural heart disease, electrolyte abnormalities and concomitant medications. Patients with hypokalaemia and advanced cardiac failure are at an increased risk for the occurrence of life-threatening ventricular arrhythmias and torsades de pointes, and fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions. Fluconazole should be administered with caution to patients with liver dysfunction, and has been associated with rare cases of serious hepatic toxicity, including fatalities, primarily in patients with serious underlying medical conditions. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored for the development of more severe hepatic injury, and fluconazole should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole. An increasing prevalence of infections with Candida species other than C. albicans has been noted, and these are often resistant or show reduced susceptibility to fluconazole, which may require alternative antifungal therapy.

Contraindications

FLUZOLE is contraindicated in patients with known sensitivity to fluconazole, related azole compounds or any of its excipients. Coadministration of terfenadine is contraindicated in patients receiving fluconazole at multiple doses of 400 mg per day or higher, and coadministration of other drugs known to prolong the QT interval and which are metabolised via the enzyme CYP3A4 such as cisapride, astemizole, erythromycin, pimozide and quinidine is contraindicated in patients receiving fluconazole. Fluconazole capsules should not be given to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Regulatory history

FLUZOLE was first registered on the Australian Register of Therapeutic Goods on 4 August 2006 as FLUZOLE ONE (150 mg capsule), with additional registrations for the 50 mg, 150 mg and 200 mg capsule strengths following on 17 August 2006.