Diltiazem with Sonidegib Interaction Details

Brand Names Associated with Diltiazem

Brand Names Associated with Sonidegib

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Increased sonidegib exposure

Interaction Summary

The concomitant use of sonidegib, a CYP3A substrate, with a moderate CYP3A inhibitor may result in increased sonidegib exposure and increase the risk of adverse effects. Based on projections from coadministration of sonidegib with ketoconazole, a strong CYP3A inhibitor, the AUC of sonidegib would increase 1.79-fold if sonidegib 200 mg once daily is coadministered with a moderate CYP3A inhibitor for 14 days and a 2.79-fold increase if coadministered for 4 months . Therefore, it is recommended that coadministration of sonidegib with a moderate CYP3A inhibitor be avoided. If coadministration cannot be avoided, concurrent use should be limited to less than 14 days and patients should be monitored closely for adverse reactions particularly musculoskeletal toxicity .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

The concurrent use of sonidegib, a CYP3A substrate, with a moderate CYP3A inhibitor may result in increased sonidegib exposure and increase the risk of adverse effects. Avoid concomitant use of sonidegib with moderate CYP3A inhibitors. If coadministration cannot be avoided, limit concurrent use to less than 14 days and monitor closely for adverse reactions particularly musculoskeletal toxicity.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of sonidegib

Literature Reports

A) In a pharmacokinetic study of 31 healthy volunteers, the mean AUC(0 to 10 days) increased 2.25-fold and the Cmax increased 1.49-fold with sonidegib 800 mg single-dose administered 5 days after initiating oral ketoconazole (a strong CYP3A inhibitor) 200 mg twice daily, compared with a single dose of sonidegib alone. Based on pharmacokinetic modeling projections, the mean AUC(0 to 24 hours) and Cmax of sonidegib would increase 1.79-fold and 1.64-fold, respectively, if sonidegib 200 mg once daily is coadministered to cancer patients with erythromycin (a moderate CYP3A inhibitor) for 14 days, and 2.79-fold and 2.43-fold, respectively, if coadministered for 4 months .

Diltiazem Overview

• Diltiazem is used to treat high blood pressure and to control angina (chest pain). Diltiazem is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart.

• High blood pressure is a common condition, and when not treated it can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Sonidegib Overview

• Sonidegib is used to treat basal cell carcinoma (BCC; a type of skin cancer) in adults with cancer that has come back after surgery or radiation, or in adults that cannot be treated with surgery or radiation. Sonidegib is in a class of medications called hedgehog pathway inhibitors. It works by blocking the action of a protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells and may help shrink tumors.

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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.