ACT FLUCONAZOLE

1 Dosing Considerations Fluconazole is well absorbed and excreted predominantly unchanged in urine following oral administration in humans. The oral bioavailability is essentially complete (greater than 90%) and is independent of dose.

Peak plasma concentrations after oral administration are attained rapidly, usually within 2 hours of dosing. Since oral absorption is rapid and almost complete, the daily dose of fluconazole is the same for oral tablets and suspension, and intravenous administration.

The terminal plasma elimination half-life is approximately 30 hours (range 20- 50 hours). The daily dose of ACT FLUCONAZOLE should be based on the infecting organism, the patient's condition and the response to therapy. Treatment should be continued until clinical parameters and laboratory tests indicate that an active fungal infection has been cured or has subsided.

An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse. 2 Recommended Dose and Dosage Adjustment RECOMMENDED DOSAGE IN ADULTS AND CHILDREN (also see 10 CLINICAL PHARMACOLOGY) TREATMENT Loading Dose ACT FLUCONAZOLE (Fluconazole Tablets) Page 6 of 58 Administration of a loading dose on the first day of treatment, consisting of twice the usual daily dose, results in plasma concentrations close to steady state by the second day.

Patients with acute infections should be given a loading dose equal to twice the daily dose, not to exceed a maximum single dose of 400 mg in adults or 12 mg/kg in children, on the first day of treatment. Dosage Equivalency Scheme Pediatric Patients Adults 3 mg/kg 100 mg 6 mg/kg 200 mg 12 mg/kg* 400 mg *Some older children may have clearances similar to that of adults.

Absolute doses exceeding 600 mg/day are not recommended. Recommended Treatment Guidelines Indication Adults Children Oropharyngeal Candidiasis 100 mg once daily for at least 2 weeks to decrease the likelihood of relapse. 3 mg/kg once daily for at least 2 weeks to decrease the likelihood of relapse.

Esophageal Candidiasis 100 mg to 200 mg once daily for a minimum of 3 weeks, and for at least 2 weeks following resolution of symptoms. 3 mg/kg to 6 mg/kg once daily for a minimum of 3 weeks, and for at least 2 weeks following resolution of symptoms.

). Driving and Operating Machinery When driving vehicles or operating machines it should be taken into account that occasionally dizziness or seizures may occur. , ketoconazole). Reversible cases of adrenal insufficiency were reported in patients while receiving fluconazole or when fluconazole was discontinued (see

Anaphylaxis In rare cases, anaphylaxis has been reported. 4 Drug-Drug Interactions – Amiodarone and Drugs prolonging the QTc interval). During post-marketing surveillance, there have been very rare cases of QT prolongation and torsade de pointes in patients taking fluconazole.

These reports included seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant medications that may have been contributory. Patients with hypokalemia and advanced cardiac failure are at an increased risk for the occurrence of life-threatening ventricular arrhythmias and torsades de pointes.

The potential for proarrhythmic events increases with co-administration of other drugs that prolong the QT interval such as some antiarrhythmics, antihistamines, psychotropic agents and antibacterials. 3 Pharmacokinetics - QT Prolongation).

Fluconazole should be administered with caution to patients with proarrhythmic conditions. 4 Drug-Drug Interactions - Drugs prolonging the QTc interval and

ACT FLUCONAZOLE is contraindicated in patients who have shown hypersensitivity to fluconazole, to any of its excipients or to related azole compounds. For a complete listing, see (6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).

Co-administration of drugs known to prolong the QT interval, and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide and quinidine are contraindicated in patients receiving fluconazole (see 9 DRUG INTERACTIONS).