Nurses Compass
Drug Guide
Ketoconazole
Classification
Therapeutic: Antifungal
Pharmacological: Imidazole antifungal
FDA Approved Indications
- Fungal infections of the skin and nails
- Seborrheic dermatitis (dandruff)
- Candidiasis, systemic (limited use due to toxicity)
Mechanism of Action
Ketoconazole inhibits fungal cytochrome P450 enzymes, impairing ergosterol synthesis which compromises fungal cell membrane integrity.
Dosage and Administration
Adult: Typically, 2% topical cream or shampoo applied as directed; oral formulations vary, but systemic use is limited due to toxicity.
Pediatric: Dosing varies by condition and age; consult specific guidelines.
Geriatric: Adjust doses if necessary; monitor for hepatic function.
Renal Impairment: No specific dose adjustment for topical use; systemic use requires caution.
Hepatic Impairment: Use with caution; systemic administration contraindicated in severe hepatic impairment.
Pharmacokinetics
Absorption: Poorly absorbed from topical preparations; systemic absorption can occur with oral and topical formulations depending on site and integrity of the skin.
Distribution: Extensively distributed in tissues, especially skin and nails.
Metabolism: Hepatic via CYP3A4 enzyme.
Excretion: Feces and urine in small amounts.
Half Life: 2 hours (topical), 20-36 hours (systemic)
Contraindications
- Hypersensitivity to ketoconazole or azole antifungals.
Precautions
- Hepatic impairment, use with caution.
- Potential for drug interactions via CYP3A4.
- Pregnancy category C; use only if clearly needed.
Adverse Reactions - Common
- Skin irritation, itching, or redness (Common)
Adverse Reactions - Serious
- Hepatotoxicity (elevated liver enzymes, hepatitis, liver failure) (Rare)
- Drug interactions leading to QT prolongation and arrhythmias (Rare)
Drug-Drug Interactions
- CYP3A4 inhibitors and inducers (e.g., rifampin, ketoconazole, clarithromycin)
- QT prolonging agents (e.g., certain antiarrhythmics)
Drug-Food Interactions
- Avoid concomitant use with substances affecting hepatic metabolism.
Drug-Herb Interactions
N/ANursing Implications
Assessment: Monitor hepatic function and for signs of hepatic toxicity; assess for skin reactions during topical therapy.
Diagnoses:
- Risk for hepatotoxicity
- Impaired skin integrity
Implementation: Administer topicals as prescribed; educate regarding proper application.
Evaluation: Monitor liver enzymes; assess for resolution or improvement of fungal infection.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report signs of liver problems (e.g., jaundice, dark urine).
- Use topical formulations as directed; avoid contact with eyes.
- Be aware of potential drug interactions.
Special Considerations
Black Box Warnings:
- Hepatotoxicity, including rare cases of liver failure.
Genetic Factors: N/A
Lab Test Interference: None significant.
Overdose Management
Signs/Symptoms: Gastrointestinal distress, dizziness, potential hepatotoxicity.
Treatment: Supportive care, monitor liver function, and symptomatic treatment.
Storage and Handling
Storage: Store at room temperature, away from moisture and light.
Stability: Stable for 2-3 years when stored properly.