Fluconazole

ADMINISTRATION ROUTES:

IV, PO

ALTERNATIVE NAMES:

Canesten Fluconazole, Diflucan, Flucazole

ICU INDICATIONS:

1. Candidiasis
2. Cryptococcal meningitis
3. Prophylaxis against Candida infections in patients after bone marrow transplantation

PRESENTATION AND ADMINISTRATION:

IV:

100 mg in 50 mL (formulated in Normal saline)

Administer undiluted solution at a constant rate not exceeding 200 mg/hr (e.g one vial over 30 minutes, or two vials over 60 minutes). Dilution is not recommended.

Fluconazole may be administered through an existing line with the following IV fluids: Hartmanns, Sodium bicarbonate, Sodium chloride, 5% Dextrose, 20% Dextrose, 20 mmol & 50 mmol KCl in 5% Dextrose

Discard any solution not used within 24 hours or opening

Do not use if solution is cloudy

Store at room temperature

PO:

Capsules:

Canesten Fluconazole 150 mg capsules (white), Diflucan 50 mg capsule (light turquoise / white), Diflucan 200 mg capsules (purple / white), Diflucan One 150 mg capsules (light turquoise blue), Flucazole 150 mg capsules (white), Fluconazole (pacific) 50 mg capsules (dark blue / white), Fluconazole (pacific) 150 mg capsules (white), Fluconazole (pacific) 200 mg capsules (blue / white)

Oral Suspension:

Diflucan suspension 50 mg/5 mL

DOSAGE:

PO & IV:

Severe infections:

400 mg stat then 200-400 mg OD

Mild infections:

200 mg stat then 100-200 mg OD

Prophylaxis:

200 - 400 mg OD (usually oral)

Note: the IV and oral dosages are the same. Fluconazole is rapidly and nearly completely absorbed when administered orally under normal circumstances

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose in renal impairment

Dose in renal replacement therapy

DOSAGE IN PAEDIATRICS:

PO & IV:

Severe infections:

12 mg/kg stat (max 800 mg) then 6-12 mg/kg OD

Mild infections:

6 mg/kg stat, then 3 mg/kg OD

Note: the IV and oral dosages are the same. Fluconazole is rapidly and nearly completely absorbed when administered orally under normal circumstances

CLINICAL PHARMACOLOGY:

Fluconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 alpha- demethylation. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. The subsequent loss of normal sterols correlates with the accumulation of 14 alpha-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole. The bioavailability of orally administered fluconazole is over 90% compared with intravenous administration.

CONTRAINDICATIONS:

1. Hypersensitivity to fluconazole

WARNINGS:

Hepatic Injury:

Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of fluconazole associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of the patient has been observed. Fluconazole hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored for the development of more severe hepatic injury. Fluconazole should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole.

Anaphylaxis:

In rare cases, anaphylaxis has been reported.

PRECAUTIONS:

General:

Patients have rarely developed exfoliative skin disorders during treatment with fluconazole. Patients who develop rashes during treatment with fluconazole should be monitored closely and the drug discontinued if lesions progress.

Laboratory Tests:

No tests in addition to routine ICU tests are required.

Drug/Laboratory Test Interactions:

None noted.

IMPORTANT DRUG INTERACTIONS IN ICU:

Clinically or potentially significant drug interactions between fluconazole and the following agents/classes have been observed. These are described in greater detail below:

Oral Hypoglycaemics:

Clinically significant hypoglycaemia may be precipitated by the use of fluconazole with oral hypoglycaemic agents: 1 fatality has been reported from hypoglycaemia in association with combined fluconazole and glyburide use. Fluconazole reduces the metabolism of tolbutamide, glyburide, and glipizide and increases the plasma concentration of these agents. When fluconazole is used concomitantly with these or other sulfonylurea oral hypoglycaemic agents, blood glucose concentrations should be carefully monitored and the dose of the sulfonylurea should be adjusted as necessary.

Warfarin:

Prothrombin time may be increased in patients receiving concomitant fluconazole and coumarin-type anticoagulants. Careful monitoring of prothrombin time in patients receiving fluconazole and coumarin-type anticoagulants is recommended.

Phenytoin:

Fluconazole increases the plasma concentrations of phenytoin. Careful monitoring of phenytoin concentrations in patients receiving fluconazole and phenytoin is recommended.

Cyclosporin:

Fluconazole may significantly increase cyclosporin levels in renal transplant patients with or without renal impairment. Careful monitoring of cyclosporin concentrations and serum creatinine is recommended in patients receiving fluconazole and cyclosporin.

Rifampin:

Rifampin enhances the metabolism of concurrently administered fluconazole. Depending on clinical circumstances, consideration should be given to increasing the dose of fluconazole when it is administered with rifampin.

Theophylline:

Fluconazole increases the serum concentrations of theophylline. Careful monitoring of serum theophylline concentrations in patients receiving fluconazole and theophylline is recommended.

ADVERSE REACTIONS:

Body as a whole:

Anaphylaxis

Gastrointestinal:

Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, hepatitis, cholestasis, fulminant hepatic failure

Neurological:

Seizures, headache

Haematological:

Leukopaenia, thrombocytopaenia

Dermatological:

Skin rash, exfoliative skin disorders including Stevens-Johnson Syndrome and toxic epidermal necrolysis