Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy

Enzalutamide is an oral androgen receptor signaling inhibitor utilized in the treatment of men with prostate cancer. It is a moderate inducer of the cytochrome P450 (CYP) enzymes CYP2C9 and CYP2C19, and a strong inducer of CYP3A4. It was also shown to be a mild inhibitor of the efflux transporter P-glycoprotein in patients with prostate cancer. Enzalutamide is primarily metabolized by CYP3A4 and CYP2C8. The risk of enzalutamide drug interactions arises primarily when it is coadministered with other drugs that interact with these CYPs, including CYP3A4. In this review, we begin by providing an overview of enzalutamide including its dosing, use in special populations, pharmacokinetics, changes to its prescribing information, and potential for interaction with coadministered drugs. Enzalutamide interactions with drugs from a wide range of medication classes commonly prescribed to patients with prostate cancer are described, including oral androgen deprivation therapy, agents used to treat a range of cardiovascular diseases, antidiabetic drugs, antidepressants, anti-seizure medications, common urology medications, analgesics, proton pump inhibitors, immunosuppressants, and antigout drugs. Enzalutamide interactions with common vitamins and supplements are also briefly discussed. This review provides a resource for healthcare practitioners and patients that will help provide a basis for the understanding and management of enzalutamide drug–drug interactions to inform decision making, improve patient safety, and optimize drug efficacy. Enzalutamide is a drug that is used to treat various stages of advanced prostate cancer, a type of cancer that begins in the prostate and may spread beyond the prostate. Enzalutamide stops testosterone from stimulating prostate cancer growth. Like other drugs, enzalutamide enters the bloodstream, and then is processed and removed from the body. Sometimes, when a person takes multiple drugs, one drug can make it difficult for the body to process and remove one or more of the other drugs. This is referred to as a drug interaction. Enzalutamide drug interactions can cause the level of other drugs in the body to increase or decrease in an abnormal way. It is also possible for certain other drugs to alter the levels of enzalutamide. Drug interactions that cause the level of a drug to get too low can prevent that drug from working effectively, whereas drug interactions that cause the level of a drug to get too high can lead to side effects of that drug. People with prostate cancer are mostly aged 65 years or older and often take medications to treat a variety of diseases. Examples include medications to treat heart conditions, diabetes, high cholesterol, high blood pressure, and many other conditions. Here, we describe enzalutamide drug interactions with these types of medications. Our goal is to provide a resource to help healthcare providers and patients better understand enzalutamide drug interactions and how to manage them to improve patient safety and drug effectiveness.