Ketoconazole with Alitretinoin Interaction Details

Brand Names Associated with Ketoconazole

Brand Names Associated with Alitretinoin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 02, 2023

Interaction Effect

Increased alitretinoin plasma concentrations

Interaction Summary

The concomitant administration of alitretinoin (a CYP3A4 substrate) with a CYP3A4 inhibitor (such as ketoconazole) may result in increased alitretinoin plasma concentrations. An analysis of 16 patients in a drug interaction study demonstrated that concomitant administration of alitretinoin and ketoconazole increased the AUC and Cmax of alitretinoin by up to 40% and up to 60%, respectively. Reduction in the dose of alitretinoin may be required with concomitant use of ketoconazole or other CYP3A4 inhibitors.

Severity

Moderate

Onset

Rapid

Evidence

Established

How To Manage Interaction

Concomitant use of alitretinoin, a CYP3A4 substrate, and ketoconazole, a CYP3A4 inhibitor, may cause increased alitretinoin plasma concentrations. Reduction in the dose of alitretinoin may be required with concomitant use of ketoconazole or other CYP3A4 inhibitors.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of alitretinoin by ketoconazole

Literature Reports

A) In a randomized, crossover, drug interaction equivalence study comparing the pharmacokinetics (PK) of alitretinoin in the presence of simvastatin, ketoconazole, and cyclosporine (n=54; age range, 18 to 45 years), an analysis of 16 patients revealed alitretinoin AUC and Cmax fell outside the margin of equivalence and were significantly increased by up to 40% and up to 60%, respectively, in the presence of ketoconazole compared with administration of alitretinoin alone. The study also examined the effects of alitretinoin administration on ketoconazole pharmacokinetics. Subjects received single and multiple doses of alitretinoin 30 mg or ketoconazole 200 mg alone and in combination. To deem the PK parameters equivalent (showing no interaction), the 90% confidence interval (CI) around the geometric mean ratio (GMR) comparing alitretinoin and ketoconazole AUC and Cmax alone and with coadministration had to fall within 0.8 to 1.25. Following multiple doses, ketoconazole AUC (GMR, 1.054; 90% CI, 0.933 to 1.193) and Cmax (GMR, 1.031; 90% CI, 0.921 to 1.157) were equivalent when administered with alitretinoin and without; however, the alitretinoin AUC and Cmax fell outside the equivalence margins when given with ketoconazole compared with administration alone, showing a significant increase in AUC (GMR, 0.718; 90% CI, 0.628 to 0.823) and Cmax (GMR, 0.654; 90% CI, 0.521 to 0.822). Alitretinoin may require a dose reduction when given in combination with ketoconazole or other CYP3A4 inhibitors .

Ketoconazole Overview

• 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.

Alitretinoin Overview

• Alitretinoin is used to treat skin lesions associated with Kaposi's sarcoma. It helps stop the growth of Kaposi's sarcoma cells.

• This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.