Sonidegib Drug Interactions: What to Avoid and What to Tell Your Doctor

Sonidegib (Odomzo) has a significant number of drug interactions that every patient and caregiver should know about. This is not a casual concern—certain medications can dramatically increase the amount of Sonidegib in your body, raising the risk of serious side effects like rhabdomyolysis, while others can reduce its effectiveness against your cancer. Here's a complete guide to Sonidegib drug interactions in 2026.

Why Sonidegib Has So Many Drug Interactions

Sonidegib is broken down (metabolized) in the body primarily by an enzyme called CYP3A (also known as CYP3A4). Many common medications either inhibit (block) or induce (speed up) this enzyme. When CYP3A is blocked, Sonidegib levels in the blood rise—sometimes dramatically. When CYP3A is sped up, Sonidegib is cleared more quickly, potentially making it less effective.

Additionally, Sonidegib affects the CYP2B6, CYP2C9 enzymes and the BCRP transporter, so it can also alter blood levels of drugs you take for other conditions.

Drugs to Avoid: Strong CYP3A Inhibitors

Strong CYP3A inhibitors can increase Sonidegib's blood levels by approximately 2.2-fold, significantly increasing the risk of toxic side effects. The FDA label states to avoid coadministration with strong CYP3A inhibitors. Examples include:

Azole antifungals: Ketoconazole, itraconazole, voriconazole, posaconazole (commonly prescribed for fungal infections)

HIV antivirals: Ritonavir, nelfinavir, lopinavir/ritonavir (commonly used in HIV treatment regimens)

Amiodarone: A heart rhythm medication — avoid concurrent use with Sonidegib due to significantly increased exposure and toxicity risk

Adagrasib: A newer targeted cancer therapy — avoid coadministration

Nefazodone: An antidepressant (rarely used now but still prescribed)

Clarithromycin and telithromycin: Macrolide antibiotics

If you need treatment for a fungal infection while on Sonidegib, ask your doctor about antifungal alternatives that don't inhibit CYP3A (such as fluconazole for some indications — but note even fluconazole is a moderate CYP3A inhibitor, so discuss with your prescriber).

Drugs to Avoid: Strong CYP3A Inducers

Strong CYP3A inducers speed up the metabolism of Sonidegib, potentially reducing its blood levels to a point where it may not be effective against your cancer. The FDA label advises against coadministration. Examples include:

Anticonvulsants: Carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital

Rifamycin antibiotics: Rifampin, rifabutin (used for tuberculosis and other infections)

St. John's Wort: This herbal supplement is a potent CYP3A inducer and should be avoided entirely during Sonidegib treatment.

Efavirenz and modafinil: An HIV antiviral and a wakefulness agent respectively — both have CYP3A inducing properties

Drugs That Increase Muscle Toxicity Risk

Due to overlapping toxicities, several drugs significantly increase the risk of muscle-related side effects (elevated CK and rhabdomyolysis) when combined with Sonidegib:

Statins (HMG-CoA reductase inhibitors): Atorvastatin (Lipitor), simvastatin, rosuvastatin (Crestor), pravastatin — very commonly prescribed for cholesterol; must be used with caution and close monitoring when combined with Sonidegib

Antimalarials: Chloroquine, hydroxychloroquine (the latter is also used for rheumatoid arthritis and lupus)

Fibric acid derivatives: Gemfibrozil, fenofibrate (used for triglycerides)

Penicillamine and zidovudine: Both are associated with muscle toxicity and should be used cautiously with Sonidegib

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Food and Supplement Interactions

Grapefruit and grapefruit juice are natural CYP3A inhibitors. While the label does not specifically list grapefruit (unlike some other drugs), the same mechanism applies—consuming large amounts of grapefruit while on Sonidegib could increase its blood levels. It's safest to avoid grapefruit juice during treatment or discuss it with your doctor.

Proton pump inhibitors (omeprazole, lansoprazole, etc.) have been studied for an interaction with Sonidegib absorption. Some research suggests they may affect how Sonidegib is absorbed. Discuss with your oncologist if you take a PPI regularly.

What to Tell Your Doctor Before Starting Sonidegib

Before starting Sonidegib, give your doctor and pharmacist a complete list of:

All prescription medications (including any other cancer drugs)

All over-the-counter medications

All vitamins and mineral supplements

All herbal supplements (especially St. John's Wort)

Your statin dose if you are on cholesterol medication

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Getting Your Medication Right

Managing drug interactions is part of using Sonidegib safely. Make sure you're also getting your prescription reliably filled by using medfinder to identify pharmacies that can fill it. And don't miss our guide on Sonidegib side effects so you know what to watch for.