Ketoconazole

Brand

Nizoral

Availability

  • Tablets: 200 mg

Pharmacology

An antifungal agent, this drug blocks the synthesis of cortisone in the adrenal gland, and interferes with the structure of the fungal cell wall. At lower doses it acts as a fungistatic, but in higher concentrations where the organism is very susceptible it may act as a fungicidal.

It is believed to be well absorbed after oral administration. Its absorption is best in an acidic environment and should not be given with H2 blockers or antacids.

Ketoconazole distributes into bile, saliva, urine, synovial fluid, and cerebral spinal fluid. Its highest levels are found in the liver, adrenals, and pituitary gland. Lesser levels are found in kidneys, lungs, bladder, bone marrow, and the mycocardium. It binds to plasma proteins and can cross the placental barrier in rats as well as in breast milk. Not recommended to be given in pregnant or nursing rats due to being teratogenic and an embryotoxin.

The drug is metabolized by the liver and excreted into the feces via bile.

Indications

Used to treat fungal infections (such as ringworm), also used to treat hyperadrenocorticism.

Drug Interactions or Contraindications

  • Antacids, anticholinergics, H2 blockers may inhibit absorption of ketoconazole.
  • Mitotane not recommended to be used with ketoconazole in treating hyperadrenocorticism.
  • Ketoconazole and phenytoin may interfere with each others absorption.
  • Ketoconazole changes the disposition, and lengthens the duration of activity by methylprednisolone.
  • Ketoconazole increases the concentration of cisapride which can lead to ventricular arrhythmias. Do not use these drugs together.
  • Serum theophylline levels are decreased when used with ketoconazole.
  • Rifampin decreases ketoconazole levels; adjust dosage if using together.

Adverse Reactions

Blood: thrombocytopenia

GI: anorexia(poor or no appetite), diarrhea, anal pruritus(itching)

Other: increased liver enzymes, hepatotoxicity

Dosage Recommendations

10 mg/kg to 40 mg/kg, PO, per day, for 14 days  27

or

10 mg/kg to 40 mg/kg, PO, q24hr for 14 days for systemic mycoses; candidiasis  34, 41

or

10 mg/kg to 40 mg/kg, PO, q24hr  35

Considerations

  • *Note: In dogs having high dose antifungal therapy, have at times during periods of acute stress, required additional glucocorticoid support*
  • Store at room temperature in tightly closed container.

Cross-references

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