Generic Name

Ketoconazole

Mechanism

Ketoconazole is a triazole antifungal that inhibits ergosterol synthesis by competitively blocking the fungal cytochrome P‑450‑dependent enzyme 14‑α‑demethylase (CYP51). Loss of ergosterol compromises cell membrane integrity, increasing permeability and ultimately causing fungal cell death. Because it targets a pathway absent in humans, systemic toxicity is low, but topical absorption can still produce rare systemic effects.

Pharmacokinetics

• Absorption: Limited systemic uptake; peak plasma concentrations usually < 10 µg/L after repeated daily applications.
• Distribution: Widely distributed within the epidermis and stratum corneum.
• Metabolism: Primarily hepatic via CYP3A4 and CYP2C19; minimal first‑pass effect with topical route.
• Excretion: Renal (≈ 30 %) and biliary.
• Half‑life: 7–9 hrs after systemic exposure; topical half‑life at the site ≥ 48 hrs.
• Drug interactions: Oral interactions (e.g., with CYP3A4 inhibitors) are irrelevant for topical therapy; concurrent use of systemic ketoconazole poses an additive hepatotoxic risk.

Indications

• Tinea corporis, cruris, versicolor, capitis (2 % cream or lotion)
• Seborrheic dermatitis (2 – 3 % cream, 2–3 % shampoo)
• Pityriasis versicolor (3 % cream/lotion)
• Cutaneous fungal infections secondary to dermatophytes or yeast in immunocompetent patients

Contraindications

• Allergy to ketoconazole or any excipient.
• Severe hepatic impairment or ongoing hepatotoxic medication may increase risk of systemic absorption.
• Pregnancy Category C: Limited data; use only if benefits outweigh risks.
• Use in infants  3 weeks) on intact skin; extended use may lead to systemic absorption and hepatotoxicity.
• Avoid application over large areas (> 10 % body surface area) or broken skin unless under supervision.

Dosing

• Wash hands after application.
• Avoid occlusion unless directed; occlusion increases absorption.
• Do not use over large body surfaces (> 10 % BSA) without medical supervision.

Adverse Effects

• Common
• Local skin irritation, pruritus, erythema, burning sensation
• Contact dermatitis (rare)
• Serious
• Hepatotoxicity (≥ 2 % in prolonged users) – manifest as jaundice, transaminitis
• Systemic absorption can produce nausea, vomiting, headache (rare)
• Rare photosensitivity

Monitoring

• Liver function tests (ALT, AST, bilirubin) if therapy > 3 weeks or in at-risk patients.
• Serious adverse reaction surveillance: check for signs of systemic toxicity (jaundice, dark urine).
• Pregnancy testing for women of child‑bearing potential.
• Clinical response: assess clearance of lesions after 2–4 weeks; adjust duration accordingly.

Clinical Pearls

• Use “2–3 %” formulations sparingly: 2 % is often adequate for most tinea and seborrheic dermatitis; 3 % is reserved for recalcitrant pityriasis versicolor or dandruff.
• Avoid simultaneous use of corticosteroids: Steroids can mask infection progression and may increase systemic absorption of ketoconazole.
• If skin irritation persists, discontinue for 48 h, then resume a reduced frequency to gauge tolerance.
• Storage: Keep in a cool, dry place; avoid humidity to prevent cream thickening.
• Patient education: Explain that topical ketoconazole does not have the safety profile of systemic ketoconazole; insist on limited surface and duration.
• Pregnancy advice: Counsel women on potential teratogenic risk and encourage use of barrier methods if exposure may occur.

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