DIFLUCAN

What it is

DIFLUCAN is a medicine containing fluconazole. It is available as gelatin capsules containing 50 mg, 100 mg, 150 mg or 200 mg fluconazole. It is also available as a solution for injection—an intravenous infusion containing fluconazole 2 mg/mL in 0.9% saline solution. A powder for oral suspension containing fluconazole 50 mg/5 mL is also available.

Approved indications

DIFLUCAN given orally is indicated for treatment of cryptococcal meningitis in patients who are unable to tolerate amphotericin B. It is indicated for maintenance therapy to prevent relapse of cryptococcal meningitis in patients with AIDS. DIFLUCAN is indicated for treatment of oropharyngeal and oesophageal candidiasis in AIDS and other immunosuppressed patients. It is indicated for secondary prophylaxis of oropharyngeal candidiasis in patients with HIV infection. DIFLUCAN is indicated for serious and life-threatening Candida infections in patients who are unable to tolerate amphotericin B. It is indicated for vaginal candidiasis when topical therapy has failed. DIFLUCAN is indicated for 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. DIFLUCAN IV is indicated for the same conditions in adults and children but should be used only when DIFLUCAN cannot be administered orally.

Dosing overview

For cryptococcal meningitis in patients unable to take or tolerate amphotericin B, the usual adult dose is 400 mg on the first day followed by 200 mg once daily, or 400 mg once daily based on medical judgement of the patient's response. For prevention of relapse of cryptococcal meningitis in AIDS patients, DIFLUCAN may be administered at a once daily dose of 100–200 mg. For oropharyngeal candidiasis, the recommended dose is 100 mg on the first day followed by 50 mg once daily. For oesophageal candidiasis, the recommended dose is 200 mg on the first day, followed by 100 mg once daily. For secondary prophylaxis against oropharyngeal candidiasis in patients with HIV infections, the recommended dose is 150 mg as a single dose once weekly. For vaginal candidiasis when topical therapy has failed, DIFLUCAN 150 mg should be administered as a single oral dose. For extensive tinea infections in immunocompetent patients in whom topical therapy is not practical, the recommended dosage is 150 mg once weekly for 4 weeks.

Key safety warnings

Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, during treatment with DIFLUCAN. Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported. 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. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsade de pointes in patients taking fluconazole. Patients with hypokalaemia and advanced cardiac failure are at an increased risk for the occurrence of life-threatening ventricular arrhythmias and torsades de pointes. Fluconazole 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 DIFLUCAN therapy should be monitored for the development of more severe hepatic injury, and DIFLUCAN should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole. Studies have shown an increasing prevalence of infections with Candida species other than C. albicans, which are often resistant (e.g., C. krusei and C. auris) or show reduced susceptibility to fluconazole (C. glabrata), and such infections may require alternative antifungal therapy secondary to treatment failure.

Contraindications

DIFLUCAN should not be used in patients with known sensitivity to fluconazole, to related azole compounds, or to any of its excipients. Coadministration of terfenadine is contraindicated in patients receiving fluconazole at multiple doses of 400 mg/day or higher. 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.

PBS listing

DIFLUCAN capsule 50 mg is listed on the PBS with streamlined restriction at an ex-manufacturer price of A$12.04. The capsule 100 mg is listed with streamlined restriction at an ex-manufacturer price of A$19.56. The capsule 200 mg is listed with streamlined restriction at an ex-manufacturer price of A$33.65. The powder for oral suspension 50 mg in 5 mL (35 mL bottle) is listed with streamlined restriction at an ex-manufacturer price of A$49.80.

Regulatory history

DIFLUCAN fluconazole 150 mg capsule was first registered on the ARTG on 14 August 1991. DIFLUCAN fluconazole 100 mg/50 mL and 200 mg/100 mL injection vials were first registered on 16 December 1993. DIFLUCAN fluconazole 50 mg, 100 mg and 200 mg capsules were first registered on 21 April 1994. DIFLUCAN fluconazole 50 mg/5 mL powder for oral suspension was first registered on 18 December 1997.