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# Ketoconazole (Systemic and Topical)
## Overview
Ketoconazole is an imidazole antifungal agent. Systemic use is severely restricted due to risk of hepatotoxicity and adrenal insufficiency. Topical formulations remain common for dermatological fungal infections.
## Primary Indications
* **Systemic:** Reserved for serious, refractory fungal infections (e.g., blastomycosis, coccidioidomycosis, histoplasmosis) where other antifungals are unavailable or contraindicated.
* **Topical:** Seborrheic dermatitis, tinea corporis, tinea cruris, tinea pedis, and pityriasis versicolor.
## Adult Dosing
* **Systemic:** 200–400 mg orally once daily. Maximum daily dose is 400 mg.
* **Topical (Cream/Gel 2%):** Apply to affected area(s) once or twice daily for 2–4 weeks.
* **Topical (Shampoo 2%):** Apply to scalp, leave for 3–5 minutes, then rinse. Use twice weekly for up to 4 weeks (at least 3 days between applications).
## Pediatric Dosing
* **Systemic:** Generally avoided. If necessary under expert guidance, 3.3–6.6 mg/kg/day orally in a single dose.
* **Topical:** Safety and efficacy in children <12 years are not established for many formulations; use per institutional protocol or specialist consultation.
## Dose Adjustments
* **Renal/Hepatic Impairment:** No specific adjustment for topical. Systemic use is strictly contraindicated in patients with acute or chronic liver disease.
## Contraindications
* **Systemic:** Known liver disease, hypersensitivity. Concurrent use with drugs that prolong QT interval (e.g., dofetilide, quinidine, pimozide, cisapride) or strong CYP3A4 inhibitors/inducers.
* **Topical:** Known hypersensitivity to ketoconazole or any component of the formulation.
## Adverse Effects
* **Systemic:** Hepatotoxicity (can be fatal), nausea, vomiting, abdominal pain, gynecomastia, impotence, decreased libido, adrenal insufficiency.
* **Topical:** Skin burning, stinging, erythema, pruritus, contact dermatitis.
## Key Drug Interactions
* **Systemic:** Strong CYP3A4 inhibitor. Inhibits metabolism of many drugs (e.g., warfarin, cyclosporine, benzodiazepines, statins), increasing risk of toxicity. Gastric acid inhibitors (PPIs, H2 blockers, antacids) significantly reduce systemic absorption; avoid concurrent use.
* **Topical:** Minimal systemic absorption, but avoid using simultaneously with potent topical corticosteroids on the same skin area to prevent interference.
## Monitoring
* **Systemic:** Baseline and periodic liver function tests (ALT, AST, bilirubin). Monitor for signs of adrenal insufficiency and drug-drug interactions.
* **Topical:** Monitor for local irritation or lack of therapeutic response.
## Clinical Pearls
* **Black Box Warning:** Oral ketoconazole is associated with hepatotoxicity, sometimes resulting in liver transplant or death. It should only be used when other effective antifungal therapy is not available or tolerated.
* **Acidity:** Oral absorption requires an acidic environment; advise patients to avoid antacids, H2 blockers, and PPIs. If acid suppression is mandatory, taking the tablet with an acidic beverage (e.g., cola) may improve absorption.
* **Topical Elegance:** Topical formulations are generally well-tolerated and lack the significant systemic side-effect profile of the oral formulation.
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*Disclaimer: This information is for educational purposes only. Clinical practice guidelines and drug information change frequently. Always verify current prescribing information, institutional protocols, and patient-specific factors before administering or prescribing any medication.*
