Ketoconazole with Colchicine Interaction Details
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Brand Names Associated with Colchicine
- Colchicine
- Colcrys®
- Gloperba®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased colchicine exposure and an increased risk of colchicine toxicity
Interaction Summary
Colchicine is a substrate of both CYP3A4 and P-gp. Concomitant use of colchicine with dual strong CYP3A4 and P-gp inhibitors is contraindicated because life-threatening and fatal colchicine toxicity has been reported in these patients with colchicine taken in therapeutic doses. Also, use of colchicine with a dual CYP3A4 and P-gp inhibitor, such as ketoconazole, is contraindicated in patients with renal or hepatic impairment . A colchicine dose adjustment is required in patients with normal renal and hepatic function who are receiving concurrently or have received ketoconazole within the last 14 days. For the treatment of gout flare, reduce the colchicine dose to one 0.6.mg tablet for one dose followed by 0.3 mg (half tablet) 1 hour later, with the repeat dose to be given no earlier than 3 days. For the prophylaxis of gout flare, reduce the colchicine dose from an original dose of 0.6 mg twice daily to 0.3 mg once daily or from an original dose of 0.6 mg once daily to 0.3 mg once every other day. For the treatment of familial Mediterranean fever, the maximum daily colchicine dose should be no more than 0.6 mg (may be given as 0.3 mg twice daily) .
Severity
Contraindicated
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of colchicine with dual strong CYP3A4 and P-glycoprotein (P-gp) inhibitors is contraindicated because life-threatening and fatal colchicine toxicity has been reported in these patients with colchicine taken in therapeutic doses. Also, use of colchicine with a dual CYP3A4 and P-gp inhibitor, such as ketoconazole, is contraindicated in patients with renal or hepatic impairment . A colchicine dose adjustment is required in patients with normal renal and hepatic function who are receiving concurrently or have received ketoconazole within the last 14 days. For the treatment of gout flare, reduce the colchicine dose to one 0.6 mg tablet for one dose followed by 0.3 mg (half tablet) 1 hour later, with the repeat dose to be given no earlier than 3 days. For the prophylaxis of gout flare, reduce the colchicine dose from an original dose of 0.6 mg twice daily to 0.3 mg once daily or from an original dose of 0.6 mg once daily to 0.3 mg once every other day. For the treatment of familial Mediterranean fever, the maximum daily colchicine dose should be no more than 0.6 mg (may be given as 0.3 mg twice daily) .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism of colchicine; and P-gp-mediated efflux transport of colchicine
Literature Reports
A) Concomitant use of a 0.6 mg dose of colchicine and ketoconazole 200 mg twice daily for 5 days resulted in 101.7% and 212.2% increases in colchicine Cmax and AUC, respectively, from baseline in a study of 24 patients .
B) Concomitant use of a 0.6 mg dose of colchicine and clarithromycin 250 mg twice daily for 7 days resulted in 227.2% and 281.5% increases in colchicine Cmax and AUC, respectively, from baseline in a study of 23 patients .
Ketoconazole Overview
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Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Colchicine Overview
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Colchicine is used to prevent gout attacks (sudden, severe pain in one or more joints caused by abnormally high levels of a substance called uric acid in the blood) in adults. Colchicine (Colcrys) is also used to relieve the pain of gout attacks when they occur. Colchicine (Colcrys) is also used to treat familial Mediterranean fever (FMF; an inborn condition that causes episodes of fever, pain, and swelling of the stomach area, lungs, and joints) in adults and children 4 years of age and older. Colchicine is not a pain reliever and cannot be used to treat pain that is not caused by gout or FMF. Colchicine is in a class of medications called anti-gout agents. It works by stopping the natural processes that cause swelling and other symptoms of gout and FMF.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.