FLUCONAZOLE IN SODIUM CHLORIDE

1 Dosing Considerations The terminal plasma elimination half-life is approximately 30 hours (range 20-50 hours). The daily dose of FLUCONAZOLE IN SODIUM CHLORIDE INJECTION USP and the route of administration should be based on the infecting organism, the patient's condition and the response to therapy.

Treatment should be continued untilclinical 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. Patientswith AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.

2 Recommended Dose and Dosage Adjustment RECOMMENDED DOSAGES IN ADULTS AND CHILDREN (also see 10 CLINICAL PHARMACOLOGY) TREATMENT Loading Dose 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.

FLUCONAZOLE IN SODIUM CHLORIDE INJECTION USP – Product Monograph Page 6 of 47 Recommended Treatment Guidelines Indication Adults Children Systemic Candidiasis (Candidemia and Disseminated Candidal Infections) 200 mg to 400 mg once daily for a minimum of 4 weeks, and for at least 2 weeks following resolution of symptoms.

6 mg/kg to 12 mg/kg per day have been used in an open, non-comparative study of a small number of patients. Cryptococcal Meningitis 200 mg to 400 mg once daily. The duration of therapy for cryptococcal meningitis is unknown, it is recommended that the initial therapy should last a minimum of 10 weeks.

6 mg/kg to 12 mg/kg once daily. The recommended duration for initial therapy is 10-12 weeks after the cerebrospinal fluid becomes culture-negative. Prevention of Recurrence of Cryptococcal Meningitis in Patients with AIDS 200 mg once daily.

6 mg/kg once daily. PREMATURE NEONATES Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns (see 10 CLINICAL PHARMACOLOGY). Based upon the prolonged half-life seen in premature newborns (gestation age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours.

After the first 2 weeks, these children should be dosed once daily. NEONATES No information regarding fluconazole pharmacokinetics in full-term newborns is available. PROPHYLAXIS IN ADULT PATIENTS The recommended FLUCONAZOLE IN SODIUM CHLORIDE INJECTION USP daily dosage for the prevention of candidiasis in adult patients undergoing bone marrow transplantation is 400 mg once daily.

Patients who are anticipated tohave severe granulocytopenia (less than 500 neutrophils/mm3) should start FLUCONAZOLE IN SODIUM CHLORIDE INJECTION USP prophylaxis several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 1000 cells/mm3.

3 Reconstitution). DOSAGE IN PATIENTS WITH IMPAIRED RENAL FUNCTION Adults Fluconazole is cleared primarily by renal excretion as unchanged drug. In patients with impaired renal function, an initial loading dose of 50 mg to 400 mg should be given (for children, see below).

34 (no dialysis) 25 Hemodialysis Hemodialysis 100 after each hemodialysis Patients on hemodialysis should receive 100% of the recommended dose after each hemodialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.

When serum creatinine is the only measure of renal function available, the following formula (based onsex, weight, and age of the patient) should be used to estimate the creatinine clearance. 85 x above value Children Although the pharmacokinetics of fluconazole have not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults.

3 Reconstitution Parenteral Products: Inspect visually for particulate matter or discoloration prior to administration. Do not use if cloudiness or precipitation is evident (see 11 […]

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

General 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 - QTProlongation).

4 Drug-Drug Interactions - Drugs prolonging the QTc interval and

FLUCONAZOLE IN SODIUM CHLORIDE INJECTION USP 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).

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