KETOZOLE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KETOZOLE (KETOZOLE).

How it works

Ketoconazole is an imidazole antifungal agent that inhibits fungal cytochrome P450 14α-demethylase, thereby blocking the conversion of lanosterol to ergosterol, a key component of the fungal cell membrane. This leads to increased membrane permeability and cell death.

What the body does with it

Metabolism	Primarily hepatic via oxidative metabolism involving CYP3A4 and to a lesser extent CYP1A2, CYP2C9, and CYP2C19. It is a potent inhibitor of CYP3A4 and CYP2C9.
Excretion	Primarily hepatic metabolism; renal excretion of unchanged drug <1%. Biliary/fecal excretion accounts for ~20-35% of metabolites.
Half-life	Terminal elimination half-life is approximately 2 hours (range 1.5–3.5 hours). Clinically, duration of antifungal effect extends beyond plasma half-life due to persistent tissue levels.
Protein binding	99% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd is approximately 3.5 L/kg (range 2–4 L/kg); indicates extensive tissue distribution with high concentrations in skin, liver, and bone.
Bioavailability	Oral bioavailability is approximately 75% (range 70–80%) after administration with a meal. Topical bioavailability: <5% systemically.
Onset of Action	Oral: Onset of antifungal effect occurs within 1–4 hours after first dose. Topical: Onset within 72 hours for dermatophyte infections.
Duration of Action	Oral: Clinical duration ~12–24 hours; requires daily dosing. Topical: Duration of action up to 72 hours after application.

Classification & Brands

Action Class	Fungal ergosterol synthesis inhibitor
Brand Substitutes	Ketofly 200mg Tablet, Ketoscalp Tablet, Ketozig 200mg Tablet, Candizone 200mg Tablet, Ketocop 200mg Tablet

Dosing & administration

200 mg orally once daily with food.

Dosage form	CREAM
Renal impairment	No adjustment required for GFR >30 mL/min. For GFR <30 mL/min, consider dose reduction to 200 mg every 48 hours.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: reduce dose to 200 mg every 48 hours.
Pediatric use	Children >2 years: 3-5 mg/kg orally once daily; maximum 200 mg.
Geriatric use	Initiate at 200 mg once daily; monitor renal and hepatic function; consider dose reduction if impaired.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KETOZOLE (KETOZOLE).

Breastfeeding	Excreted into breast milk in small amounts; M/P ratio unknown. Clinical significance uncertain; manufacturer advises caution due to potential for infant exposure and adverse effects (e.g., hepatic toxicity, endocrine disruption). Consider interruption of breastfeeding during therapy.
Teratogenic Risk	First trimester: Crosses placenta; animal studies show teratogenicity at high doses; limited human data preclude risk quantification but suggest possible increased risk of congenital anomalies, particularly skeletal and craniofacial defects. Second/third trimester: Potential for fetal adrenal suppression with prolonged use; reports of preterm birth, low birth weight; avoid unless essential.

Warnings & precautions

■ FDA Black Box Warning

Hepatotoxicity: Ketoconazole has been associated with severe hepatotoxicity, including fatal cases. Use only when other antifungal therapies are not available or tolerated. Monitor liver function tests frequently. Contraindicated in patients with acute or chronic liver disease.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Acute or chronic liver disease","Concomitant administration with drugs that are highly dependent on CYP3A4 metabolism and have narrow therapeutic indices (e.g., ergot derivatives, triazolam, midazolam, HMG-CoA reductase inhibitors metabolized by CYP3A4)","Concomitant administration with drugs that prolong QT interval","Known hypersensitivity to ketoconazole or any excipients"]

Clinical Precautions

Precautions

["Hepatotoxicity (see black box warning)","QT interval prolongation: May prolong QT interval; avoid use with other QT-prolonging drugs or in patients with electrolyte disturbances or bradycardia","Adrenal insufficiency: Inhibits adrenal steroidogenesis; may cause adrenal suppression with prolonged use","Drug interactions: Potent CYP3A4 inhibitor; contraindicated with certain drugs (e.g., ergot alkaloids, midazolam, certain statins)","Gastrointestinal disturbances: Nausea, vomiting, abdominal pain"]

Clinical Tips & Counseling

Drug interactions

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KETOZOLE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KETOZOLE (KETOZOLE).

How it works

What the body does with it

Metabolism	Primarily hepatic via oxidative metabolism involving CYP3A4 and to a lesser extent CYP1A2, CYP2C9, and CYP2C19. It is a potent inhibitor of CYP3A4 and CYP2C9.
Excretion	Primarily hepatic metabolism; renal excretion of unchanged drug <1%. Biliary/fecal excretion accounts for ~20-35% of metabolites.
Half-life	Terminal elimination half-life is approximately 2 hours (range 1.5–3.5 hours). Clinically, duration of antifungal effect extends beyond plasma half-life due to persistent tissue levels.
Protein binding	99% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd is approximately 3.5 L/kg (range 2–4 L/kg); indicates extensive tissue distribution with high concentrations in skin, liver, and bone.
Bioavailability	Oral bioavailability is approximately 75% (range 70–80%) after administration with a meal. Topical bioavailability: <5% systemically.
Onset of Action	Oral: Onset of antifungal effect occurs within 1–4 hours after first dose. Topical: Onset within 72 hours for dermatophyte infections.
Duration of Action	Oral: Clinical duration ~12–24 hours; requires daily dosing. Topical: Duration of action up to 72 hours after application.

Classification & Brands

Action Class	Fungal ergosterol synthesis inhibitor
Brand Substitutes	Ketofly 200mg Tablet, Ketoscalp Tablet, Ketozig 200mg Tablet, Candizone 200mg Tablet, Ketocop 200mg Tablet

Dosing & administration

200 mg orally once daily with food.

Dosage form	CREAM
Renal impairment	No adjustment required for GFR >30 mL/min. For GFR <30 mL/min, consider dose reduction to 200 mg every 48 hours.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: reduce dose to 200 mg every 48 hours.
Pediatric use	Children >2 years: 3-5 mg/kg orally once daily; maximum 200 mg.
Geriatric use	Initiate at 200 mg once daily; monitor renal and hepatic function; consider dose reduction if impaired.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KETOZOLE (KETOZOLE).

Breastfeeding	Excreted into breast milk in small amounts; M/P ratio unknown. Clinical significance uncertain; manufacturer advises caution due to potential for infant exposure and adverse effects (e.g., hepatic toxicity, endocrine disruption). Consider interruption of breastfeeding during therapy.
Teratogenic Risk	First trimester: Crosses placenta; animal studies show teratogenicity at high doses; limited human data preclude risk quantification but suggest possible increased risk of congenital anomalies, particularly skeletal and craniofacial defects. Second/third trimester: Potential for fetal adrenal suppression with prolonged use; reports of preterm birth, low birth weight; avoid unless essential.