Home
BackKetoconazole Data - Uses, Dosage, Drug class, Brand name, Warnings, etc
| Pharmacology | Ketoconazole, an imidazole antifungal, inhibits fungal cytochrome P450, blocking ergosterol synthesis and disrupting fungal cell membranes. It is used for mucocutaneous fungal infections (e.g., candidiasis, tinea versicolor) and systemic infections (blastomycosis, histoplasmosis, paracoccidioidomycosis) in immunocompetent patients. It suppresses but does not eliminate coccidioidomycosis. Poor CSF penetration makes it unsuitable for CNS fungal infections. It also inhibits steroid synthesis, used off-label for prostatic cancer and Cushing syndrome. |
|---|---|
| Administration and Adult Dosage |
- PO: 200–400 mg daily or twice daily, based on infection site/severity - Topical (cream): Apply once or twice daily for dermatophytoses, superficial mycoses, or seborrheic dermatitis - Topical (shampoo): Apply twice weekly for 4 weeks for dandruff |
| Special Populations - Pediatric Dosage |
- PO: • <2 yr: Not established • ≥2 yr: 3.3–6.6 mg/kg/day in 1–2 divided doses; tablets may be crushed and mixed with applesauce/juice - Topical (cream): Apply once daily |
| Special Populations - Geriatric Dosage | Same as adult dosage. |
| Other Conditions |
- Hepatic impairment: Limited data suggest no adjustment needed; definitive studies lacking - Renal dysfunction: No dosage adjustment required |
| Dosage Forms |
- Tablet: 200 mg - Cream: 2% - Shampoo: 1%, 2% |
| Patient Instructions |
- Take oral dose with meals if stomach upset occurs; avoid antacids, H2-blockers, or proton-pump inhibitors - Report fatigue, loss of appetite, nausea, vomiting, yellowing of skin, dark urine, or pale stools - Take with an acidic beverage (e.g., cola) to enhance absorption - For 0.1 N HCl administration, sip through a straw to protect teeth - Apply topical cream/shampoo sparingly to affected areas |
| Missed Doses | - Take missed dose as soon as remembered; if near next dose, take only that dose, leaving ≥12 hr between doses; do not double dose |
| Pharmacokinetics - Fate |
- Bioavailability: ~75%, dose-dependent; reduced 20–40% with food, further decreased with elevated gastric pH - Peak Levels: 3.4 ± 0.3 mg/L (6.4 ± 0.6 µmol/L) post 200 mg with meal - Protein Binding: 93–96% - Distribution: Vd = 0.36 ± 0.1 L/kg (single dose), 2.4 ± 1.6 L/kg (long-term) - Clearance: Cl = 0.5 ± 0.25 L/hr/kg (long-term) - Metabolism: Extensive hepatic metabolism to inactive metabolites - Excretion: 2–4% unchanged in urine |
| Pharmacokinetics - t¹⁄₂ | - 8.7 ± 0.2 hr (single dose); 3.3 ± 1 hr (long-term therapy) |
| Adverse Reactions & Side Effects |
Frequent: - Nausea, vomiting, pruritus, abdominal discomfort, mild transaminase elevations Occasional: - Hepatotoxicity (including rare massive hepatic necrosis) - Gynecomastia (due to testosterone synthesis suppression) Rare: - Hypoadrenalism (from cortisol synthesis inhibition) Topical: - Irritation, pruritus, stinging |
| Contraindications | - Coadministration with astemizole or cisapride |
| Precautions & Warnings |
- Use cautiously in pregnancy, lactation - Monitor for hepatotoxicity, especially in hepatic impairment - Avoid in patients with achlorhydria unless coadministered with acidic solutions |
| Drug Interactions |
- Inhibits CYP3A4, increasing levels of cyclosporine, methylprednisolone, warfarin, and contraindicated drugs (astemizole, cisapride) - Warfarin: May require dose reduction - H2-blockers, antacids, proton-pump inhibitors (e.g., omeprazole, lansoprazole) reduce oral absorption |
| Parameters to Monitor |
- Liver function tests before and frequently during therapy - Prothrombin time with concurrent warfarin - Cyclosporine levels if coadministered - Signs of hepatotoxicity or adrenal insufficiency |
| Class and Drug Brand Name |
- Class: Imidazole Antifungals - Brand Name: Nizoral |
| Notes |
- Achlorhydric patients: Administer with glutamic acid hydrochloride, 0.1 N HCl (via straw), or acidic drink (e.g., cola) to increase absorption by ~65% - Primarily for mucocutaneous infections; less effective for CNS infections due to poor CSF penetration - Off-label use in prostatic cancer and Cushing syndrome due to steroid synthesis inhibition |
References
Hand of Clinical Drug Data