What it's for (Indications)
- Ketoconazole is used for systemic mycoses (internal fungal infections) and prophylaxis of mycoses in patients with reduced immune responses.
- It should only be used when other effective antifungal therapy is not available or tolerated, and the potential benefits are considered to outweigh the potential risks, especially considering it is not indicated for treatment of onychomycosis, cutaneous dermatophyte infections, or Candida infections.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Clinical and laboratory documentation of infection is required before starting ketoconazole therapy. The usual duration of therapy for systemic infection is 6 months, continuing until the active fungal infection has subsided. For adults, the recommended starting dose is 200 mg once daily. If clinical responsiveness is insufficient within the expected time, the dose may be increased to 400 mg once daily. For children over 2 years of age, a single daily dose of 3.3 to 6.6 mg/kg has been used. Ketoconazole tablets have not been studied in children under 2 years of age. |
Safety & Warnings
Common Side Effects
- Common adverse reactions include stomach upset, headache, rashes, nausea, vomiting, diarrhea, constipation, abdominal pain (including upper abdominal pain), dyspepsia, flatulence, dry mouth, dysgeusia, and tongue discoloration.
- Other reported adverse reactions include anaphylactoid reaction, gynecomastia, alcohol intolerance, anorexia, hyperlipidemia, increased appetite, insomnia, nervousness, dizziness, paresthesia, somnolence, photophobia, orthostatic hypotension, and epistaxis.
- Serious adverse reactions include hepatitis and jaundice.
Serious Warnings
- Black Box Warning: Because ketoconazole tablets have been associated with serious adverse reactions, including serious hepatotoxicity (which can be fatal), ketoconazole tablets are not indicated for treatment of onychomycosis, cutaneous dermatophyte infections, or Candida infections. Ketoconazole tablets should be used only when other effective antifungal therapy is not available or tolerated, and the potential benefits are considered to outweigh the potential risks.
- Ketoconazole is associated with serious hepatotoxicity, including cases with a fatal outcome.
- It is not recommended in pre-existing liver disease or significant abnormalities on liver function tests.
- Patients should be monitored for signs of liver damage, with liver function tests suggested after the first 10 days of treatment and then twice per month.
- Pregnant women should avoid this medicine, and it is not recommended for women who are breastfeeding.
- Patients should avoid consuming alcohol when taking this medicine due to potential alcohol intolerance and increased risk of liver damage.
How it Works (Mechanism of Action)
Ketoconazole blocks the synthesis of ergosterol, a key component of the fungal cell membrane, by inhibiting cytochrome P-450 dependent enzyme lanosterol 14α-demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, leading to an accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane, thereby weakening its structure and function.