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

Orgovyx (relugolix) has several clinically significant drug interactions that patients and their healthcare providers need to manage carefully. Understanding these interactions helps prevent reduced effectiveness, dangerous side effects, or other complications. This guide covers the most important interactions, why they occur, and what to do about them.

Important: Always share a complete list of your medications — including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements — with every healthcare provider who manages your care.

How Orgovyx Is Processed in the Body

Orgovyx (relugolix) is metabolized by the CYP3A enzyme system in the liver and is transported by P-glycoprotein (P-gp). Understanding these pathways explains why certain drug categories interact with it:

P-gp substrate: P-glycoprotein transports relugolix out of intestinal cells into the gut (reducing absorption) and out of liver cells. Drugs that inhibit P-gp increase relugolix absorption and blood levels.

CYP3A substrate: Drugs that strongly induce CYP3A enzymes increase the metabolism (breakdown) of relugolix, lowering blood levels and potentially reducing its effectiveness.

Interaction Category 1: P-gp Inhibitors (AVOID or Use With Caution)

P-glycoprotein (P-gp) inhibitors increase the blood levels of Orgovyx (relugolix), which can increase the risk of adverse effects. The prescribing information recommends avoiding co-administration of Orgovyx with oral P-gp inhibitors.

If co-administration is unavoidable:

Take Orgovyx first, then wait at least 6 hours before taking the P-gp inhibitor

Monitor closely for increased adverse reactions

If a short course (up to 2 weeks) of a P-gp inhibitor is needed, Orgovyx may be temporarily interrupted; restart with a 360 mg loading dose if treatment is paused >7 days

Common P-gp inhibitors to be aware of include:

Amiodarone (heart rhythm medication)

Azithromycin (Z-Pack antibiotic)

Clarithromycin (antibiotic)

Cyclosporine (immunosuppressant)

Ketoconazole (antifungal)

Dronedarone (heart medication)

Itraconazole (antifungal)

Interaction Category 2: Combined P-gp and Strong CYP3A Inducers (AVOID)

Drugs that are both P-gp substrates and strong CYP3A inducers reduce relugolix blood levels significantly, potentially making Orgovyx less effective at suppressing testosterone. Avoid these combinations. If co-administration is unavoidable, the Orgovyx dose should be increased to 240 mg once daily; return to 120 mg once the inducer is discontinued.

Key drugs in this category:

Rifampin (antibiotic used for tuberculosis)

Carbamazepine (antiseizure medication)

Phenytoin (antiseizure medication)

St. John's Wort (herbal supplement — commonly overlooked)

Interaction Category 3: QT-Prolonging Medications (Monitor Carefully)

Orgovyx itself can prolong the QT/QTc interval on an ECG, which can increase the risk of dangerous heart arrhythmias like torsades de pointes. When combined with other QT-prolonging medications, this risk is additive. If you take any of the following, your doctor should monitor your ECG and electrolytes:

Antiarrhythmics: amiodarone, dronedarone, sotalol, procainamide, quinidine

Antipsychotics: haloperidol, risperidone, chlorpromazine

Antibiotics: moxifloxacin, azithromycin (also a P-gp inhibitor), clarithromycin

Antidepressants: certain tricyclics, citalopram, escitalopram at higher doses

Antiemetics: ondansetron (Zofran), metoclopramide

Other ADT-Related Metabolic Interactions

Because Orgovyx suppresses testosterone and can raise blood glucose and triglycerides, patients on:

Antidiabetes medications (metformin, insulin, GLP-1 agonists) may need dose adjustments as blood glucose increases with ADT.

Statins or cholesterol medications — lipid levels should be monitored, as ADT can affect the lipid profile.

Herbal Supplements and Orgovyx

Many patients don't realize that herbal supplements can interact with prescription medications. Specifically for Orgovyx, be aware of:

St. John's Wort: A significant P-gp and CYP3A inducer that can substantially reduce Orgovyx blood levels. Avoid completely.

Ginseng and other supplements marketed to boost testosterone: Counterproductive when the goal of Orgovyx is to suppress testosterone.

What to Tell Your Doctor and Pharmacist

Before starting Orgovyx, tell your prescriber and pharmacist about all medications you take — including any new prescriptions added by other providers (cardiologists, primary care physicians, etc.). Any new QT-prolonging, P-gp inhibitor, or CYP3A inducer added during your Orgovyx treatment should trigger a check with your oncologist or pharmacist. For more on Orgovyx side effects, see our guide to Orgovyx side effects. If you need help filling your Orgovyx prescription, visit medfinder.com.