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Ketoconazole (Systemic)

Prescription

Imidazole Antifungal

Last reviewed 21 Apr 2026 · PetCare.AI Editorial Team

Species

Dog, Cat

Brands

1 available

Interactions

11 documented

Formulations

Mechanism of action

Inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking ergosterol synthesis. Also inhibits mammalian CYP450 enzymes including adrenal steroidogenesis — used therapeutically to reduce cortisol in Cushing's disease and to boost cyclosporine levels.

At a glance

Class

Imidazole Antifungal

Schedule

Prescription

Storage

Store at room temperature below 25°C

Dosing

🐕

Dog

Three uses: (1) systemic antifungal (Malassezia, dermatophytes — largely replace

Dose

5–10 mg/kg

Route

Frequency

q12–24h

🐈

Cat

Cats tolerate ketoconazole poorly — hepatotoxicity and anorexia common

Dose

5–10 mg/kg

Route

Frequency

q12–24h

Formulations

💊

Other — 1

Strength

—

Storage

Store at room temperature below 25°C

Safety

Monitoring parameters

Hepatic enzymes q2 weeks initially then monthlyACTH stimulation test (Cushing's use)GI toleranceDrug interaction review

Interactions

Contraindicated — 1

Cisapride

contraindicated

Ketoconazole inhibits CYP3A4 metabolism of cisapride, causing dangerous cisapride accumulation and fatal QT prolongation/ventricular arrhythmias.

Management: NEVER combine. Use alternative prokinetic (metoclopramide) or alternative antifungal (fluconazole has less CYP3A4 inhibition).

Major — 6

Rifampicin

major

Rifampicin induces CYP3A4 metabolism of ketoconazole, dramatically reducing ketoconazole levels. Ketoconazole inhibits rifampicin absorption. Bidirectional antagonism.

Management: Avoid combination — both drugs lose efficacy. Use alternative antifungal or alternative antimycobacterial.

Alprazolam

major

Ketoconazole potently inhibits CYP3A4, increasing alprazolam levels 2-3 fold causing excessive prolonged sedation.

Management: Avoid or reduce alprazolam by 50-75%. Use lorazepam instead (glucuronidation pathway — not CYP-dependent).

Budesonide

major

Budesonide relies on CYP3A4-mediated first-pass metabolism for low systemic bioavailability. Ketoconazole inhibits CYP3A4, dramatically increasing systemic budesonide exposure (up to 6-fold), causing iatrogenic Cushing's syndrome.

Management: Avoid combination. If concurrent antifungal needed with budesonide, use fluconazole (less CYP3A4 inhibition) or terbinafine.

Alfentanil

major

Alfentanil is entirely CYP3A4 metabolized. Ketoconazole inhibits CYP3A4, dramatically increasing alfentanil levels and duration, causing prolonged respiratory depression.

Management: Reduce alfentanil dose by 50-75% if ketoconazole on board. Have ventilatory support ready. Monitor respiratory function closely.

Colchicine

major

Colchicine is a CYP3A4 and P-glycoprotein substrate. Ketoconazole inhibits both, causing colchicine accumulation and severe toxicity (myelosuppression, multi-organ failure).

Management: Avoid combination. If concurrent use unavoidable, reduce colchicine dose by 50-75% and monitor CBC closely.

Domperidone

major

Ketoconazole inhibits CYP3A4 metabolism of domperidone, increasing levels. Domperidone causes dose-dependent QT prolongation — elevated levels increase cardiac arrhythmia risk.

Management: Avoid combination. If prokinetic needed with ketoconazole, use metoclopramide (not CYP3A4 substrate).

Moderate — 4

Cyclosporine (Systemic)

moderate

Ketoconazole potently inhibits CYP3A4 and P-glycoprotein, increasing cyclosporine levels 2-3 fold. Used therapeutically to reduce cyclosporine cost.

Management: When intentional: reduce cyclosporine dose by 50-75% and monitor trough levels. When unintentional: monitor for cyclosporine toxicity (vomiting, nephrotoxicity).

Trilostane

moderate

Both ketoconazole and trilostane inhibit adrenal steroidogenesis. Combined use may cause profound hypocortisolism.

Management: Avoid concurrent use. If transitioning between agents, monitor ACTH stimulation test closely.

Isoniazid (INH)

moderate

Isoniazid may reduce ketoconazole absorption. Ketoconazole requires acidic gastric pH for dissolution — isoniazid may alter this.

Management: Separate by 2 hours. Monitor antifungal response.

Vinblastine

moderate

Ketoconazole inhibits CYP3A4 and P-glycoprotein, potentially increasing vinblastine levels and myelosuppression.

Management: Monitor CBC more closely. Consider dose reduction of vinblastine.

Brands

Other markets

Nizoral

FAQs

Frequently asked questions

›What is Ketoconazole (Systemic)?

Ketoconazole (Systemic) is a imidazole antifungal used in pets. Inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking ergosterol synthesis. Also inhibits mammalian CYP450 enzymes including adrenal steroidogenesis — used therapeutically to reduce cortisol in Cushing's disease and to boost cyclosporine levels.

›What is Ketoconazole (Systemic) used for in pets?

Ketoconazole (Systemic) is used in veterinary medicine for: Three uses: (1) systemic antifungal (Malassezia, dermatophytes — largely replace; Cats tolerate ketoconazole poorly — hepatotoxicity and anorexia common.

›What is the Ketoconazole (Systemic) dose for dogs?

For dogs, Ketoconazole (Systemic) is typically dosed as follows — Three uses: (1) systemic antifungal (Malassezia, dermatophytes — largely replace: 5–10 mg/kg PO q12–24h. Always consult your veterinarian for a dose tailored to your pet's weight, age, and condition.

›What is the Ketoconazole (Systemic) dose for cats?

For cats, Ketoconazole (Systemic) is typically dosed as follows — Cats tolerate ketoconazole poorly — hepatotoxicity and anorexia common: 5–10 mg/kg PO q12–24h. Always consult your veterinarian for a dose tailored to your pet's weight, age, and condition.

›Does Ketoconazole (Systemic) need a prescription?

Yes. Ketoconazole (Systemic) is a prescription medication and should only be administered under veterinary supervision.

References

CDSCO approvals (India) — 1

Ketoconazole IP 1.0 %w/w + Chlorhexidine Gluconate Solution IP Eq. to Chlorhexid

M/s. Gopaldas & Vishramdas · Approved 30.04.2015

For management of problems related with bacterial and fungal dermatitis of dogs and cats.

Source: CDSCO Veterinary Drug Approval Registry (1969–2026)

References

Textbooks & handbooks

Plumb, D.C. Plumb's Veterinary Drug Handbook. 10th ed., Wiley-Blackwell, 2023.
Vail, D.M., Thamm, D.H., & Liptak, J.M. (eds.). Withrow & MacEwen's Small Animal Clinical Oncology. 6th ed., Saunders/Elsevier, 2020.
Riviere, J.E., & Papich, M.G. (eds.). Veterinary Pharmacology and Therapeutics. 10th ed., Wiley-Blackwell, 2018.
National Research Council. Nutrient Requirements of Dogs and Cats. National Academies Press, Washington DC, 2006.
The Merck Veterinary Manual. Merck & Co., Online edition. https://www.merckvetmanual.com/

Clinical guidelines & consensus

Fletcher, D.J., Boller, M., Brainard, B.M., et al. "RECOVER Evidence and Knowledge Gap Analysis on Veterinary CPR." Journal of Veterinary Emergency and Critical Care, 2012;22(S1):S102–S131.
American Animal Hospital Association. 2018 AAHA Diabetes Management Guidelines for Dogs and Cats. AAHA Press.

Journals & peer-reviewed studies

Hogan, D.F., Fox, P.R., Jacob, K., et al. "Secondary prevention of cardiogenic arterial thromboembolism in the cat: The FAT CAT study." Journal of Veterinary Cardiology, 2015;17(Suppl 1):S306–S317.
Boswood, A., Häggström, J., Gordon, S.G., et al. "Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study — A Randomized Clinical Trial." Journal of Veterinary Internal Medicine, 2016;30(6):1765–1779.
ASPCA Animal Poison Control Center. Toxicology and Poison Management Guidelines. American Society for the Prevention of Cruelty to Animals. https://www.aspca.org/pet-care/animal-poison-control

Regulatory & approvals

Central Drugs Standard Control Organisation (CDSCO), Government of India. Veterinary Drug Approval Registry, 1969–2026. Directorate General of Health Services. https://cdsco.gov.in/

Databases

Washington State University, College of Veterinary Medicine. Veterinary Clinical Pharmacology Laboratory (VCPL) — MDR1 Multidrug Sensitivity Database. https://vcpl.vetmed.wsu.edu/

Educational reference only

This information is provided for educational purposes and is not a substitute for professional veterinary advice, diagnosis, or treatment. Always consult a qualified veterinarian before administering any medication to your pet. Find a vet near you →

Related medicines

Other medicines in the same class (Imidazole Antifungal).

Clotrimazole

Inhibits ergosterol synthesis by blocking lanosterol 14-alpha demethylase (CYP51), disrupting fungal cell membrane integrity

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Ketoconazole

Inhibits fungal CYP450 lanosterol 14-alpha-demethylase; also inhibits mammalian steroidogenesis (cortisol, testosterone), used off-label for Cushing's disease

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Miconazole

Inhibits ergosterol synthesis by blocking 14-alpha-demethylase, disrupting fungal cell membrane integrity

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