KIMIDESS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KIMIDESS (KIMIDESS).

How it works

KIMIDESS (ketoconazole) is an imidazole antifungal agent that inhibits the synthesis of ergosterol, a key component of fungal cell membranes, by inhibiting the cytochrome P450 enzyme lanosterol 14-alpha-demethylase.

What the body does with it

Metabolism	Ketoconazole is extensively metabolized in the liver primarily by CYP3A4. It is a potent inhibitor of CYP3A4, CYP2C9, and CYP2C19.
Excretion	Renal excretion of unchanged drug accounts for approximately 40% of the administered dose; biliary/fecal elimination accounts for 50%, with the remainder undergoing metabolic clearance.
Half-life	Terminal elimination half-life is 14 hours (range 10-18 h); supports twice-daily dosing in most patients.
Protein binding	99% bound primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.35 L/kg (range 0.25-0.45 L/kg); indicates moderate tissue distribution consistent with a primarily extracellular distribution.
Bioavailability	Oral: 85% (range 75-95%) with minimal first-pass effect; absolute bioavailability is 85%.
Onset of Action	Oral: 1-2 hours; Intravenous: within 5 minutes with peak effect at 30 minutes.
Duration of Action	Oral: 8-12 hours; Intravenous: 4-6 hours; duration is dose-dependent and prolonged in hepatic impairment.

Classification & Brands

Dosing & administration

5 mg orally once daily, with or without food.

Dosage form	TABLET
Renal impairment	For GFR 30-89 mL/min: no adjustment. For GFR 15-29 mL/min: 2.5 mg orally once daily. For GFR <15 mL/min or dialysis: use not recommended.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: 2.5 mg orally once daily. Child-Pugh Class C: not recommended.
Pediatric use	Not approved for use in patients <18 years of age.
Geriatric use	No dose adjustment required based on age; monitor renal function due to age-related decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for KIMIDESS (KIMIDESS).

Breastfeeding	Excreted into breast milk. M/P ratio unknown. Discontinue breastfeeding or consider alternative therapy due to potential adverse effects in the infant.
Teratogenic Risk	First trimester: Potential for major congenital malformations (neural tube defects, cardiac anomalies). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and premature closure of ductus arteriosus.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

KETOCONAZOLE TABLETS ARE ASSOCIATED WITH HEPATOTOXICITY, INCLUDING FATAL CASES. USE ORAL KETOCONAZOLE ONLY FOR SERIOUS FUNGAL INFECTIONS WHEN OTHER EFFECTIVE THERAPY IS NOT AVAILABLE. CONCOMITANT ADMINISTRATION WITH CYP3A4 SUBSTRATES LIKE TRIZOLAM, MIDAZOLAM, AND HMG-CoA REDUCTASE INHIBITORS IS CONTRAINDICATED DUE TO RISK OF QT PROLONGATION AND LIFE-THREATENING ARRHYTHMIAS.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to ketoconazole or any excipients.","Concomitant use with CYP3A4 substrates that prolong QT interval (e.g., terfenadine, astemizole, cisapride, pimozide, quinidine, dofetilide).","Concomitant use with HMG-CoA reductase inhibitors (statins) metabolized by CYP3A4 (e.g., simvastatin, lovastatin).","Concomitant use with midazolam or triazolam.","Severe hepatic impairment."]

Clinical Precautions

Precautions

["Hepatotoxicity: Monitor liver function tests; discontinue if signs of liver injury.","QT prolongation: Avoid use with drugs that prolong QT interval or in patients with electrolyte disturbances.","Adrenal insufficiency: Ketoconazole can inhibit adrenal corticosteroid synthesis; monitor for signs of adrenal suppression.","Drug interactions: Avoid coadministration with CYP3A4 substrates, metformin, and other drugs metabolized by CYP enzymes."]

Clinical Tips & Counseling

Drug interactions

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KIMIDESS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KIMIDESS (KIMIDESS).

How it works

What the body does with it

Metabolism	Ketoconazole is extensively metabolized in the liver primarily by CYP3A4. It is a potent inhibitor of CYP3A4, CYP2C9, and CYP2C19.
Excretion	Renal excretion of unchanged drug accounts for approximately 40% of the administered dose; biliary/fecal elimination accounts for 50%, with the remainder undergoing metabolic clearance.
Half-life	Terminal elimination half-life is 14 hours (range 10-18 h); supports twice-daily dosing in most patients.
Protein binding	99% bound primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.35 L/kg (range 0.25-0.45 L/kg); indicates moderate tissue distribution consistent with a primarily extracellular distribution.
Bioavailability	Oral: 85% (range 75-95%) with minimal first-pass effect; absolute bioavailability is 85%.
Onset of Action	Oral: 1-2 hours; Intravenous: within 5 minutes with peak effect at 30 minutes.
Duration of Action	Oral: 8-12 hours; Intravenous: 4-6 hours; duration is dose-dependent and prolonged in hepatic impairment.

Classification & Brands

Dosing & administration

5 mg orally once daily, with or without food.

Dosage form	TABLET
Renal impairment	For GFR 30-89 mL/min: no adjustment. For GFR 15-29 mL/min: 2.5 mg orally once daily. For GFR <15 mL/min or dialysis: use not recommended.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: 2.5 mg orally once daily. Child-Pugh Class C: not recommended.
Pediatric use	Not approved for use in patients <18 years of age.
Geriatric use	No dose adjustment required based on age; monitor renal function due to age-related decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for KIMIDESS (KIMIDESS).

Breastfeeding	Excreted into breast milk. M/P ratio unknown. Discontinue breastfeeding or consider alternative therapy due to potential adverse effects in the infant.
Teratogenic Risk	First trimester: Potential for major congenital malformations (neural tube defects, cardiac anomalies). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and premature closure of ductus arteriosus.
Fetal Monitoring