Fluconazole

Fluconazole

[100mg IV $7.10; 200mg tablet 68 cents]

ADMINISTRATION ROUTES:

• IV, PO

ALTERNATIVE NAMES:

• Canesten Fluconazole, Diflucan, Flucazole

ICU INDICATIONS:

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

PRESENTATION AND ADMINISTRATION:

• IV:
  50mg in 100ml (formulated in normal saline)
  Administer undiluted solution at a constant rate not exceeding 200mg/hr (eg 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 chlorid,e 5%dextros,e 20%dextrose, 20mmol & 50mmol 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 150mg capsules (white), Diflucan 50mg capsule (light turquoise / white), Diflucan 200mg capsules (purple / white), Diflucan One 150mg capsules (light turquoise blue), Flucazole 150mg capsules (white), Fluconazole (pacific) 50mg capsules (dark blue / white), Fluconazole (pacific) 150mg capsules (white), Fluconazole (pacific) 200mg capsules (blue / white)
  Oral Suspension:
  Diflucan suspension 50mg/5ml

DOSAGE:

• PO & IV:
  Severe infections:
  400mg stat then 200-400mg daily
  Mild infections:
  200mg stat then 100-200mg daily
  Prophylaxis:
  200mg – 400mg daily (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 [GFR (ml/min)]
  <10: 50% of normal dose
  10-20: dose as in normal renal function
  >20-50: dose as in normal renal function
• Dose in renal replacement therapy:
  CAPD: 50% of normal dose
  HD: 50% of normal dose; give post dialysis
  CVVHDF: dose as in normal renal function

DOSAGE IN PAEDIATRICS:

• IV and PO:
  Severe infections:
  12mg/kg stat (max 800mg), then 6-12mg/kg daily
  Mild infections:
  6mg/kg stat, then 3mg/kg daily

  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 FOR THE 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 Hypoglycemics:
  Clinically significant hypoglycemia may be precipitated by the use of fluconazole with oral hypoglycemic agents: 1 fatality has been reported from hypoglycemia 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 hypoglycemic 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.
  Cyclosporine:
  Fluconazole may significantly increase cyclosporine levels in renal transplant patients with or without renal impairment. Careful monitoring of cyclosporine concentrations and serum creatinine is recommended in patients receiving fluconazole and cyclosporine.
  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:
  Leukopenia, thrombocytopenia
• Dermatological:
  Skin rash, exfoliative skin disorders including Stevens-Johnson Syndrome and toxic epidermal necrolvsis