Learn about Orilissa drug interactions — which medications to avoid, OTC and supplement concerns, and what to tell your doctor before starting treatment.
If you're taking Orilissa (Elagolix) for endometriosis, it's important to understand how it interacts with other medications. Some interactions are serious enough that certain drugs are completely off-limits while you're on Orilissa. Others just need monitoring.
This guide covers major and moderate drug interactions, supplements and OTC medications to watch for, and exactly what to tell your doctor before starting treatment.
Orilissa is processed by your liver using specific enzyme pathways — primarily CYP3A4 — and it's also transported by proteins called OATP1B1 and P-glycoprotein (P-gp). Medications that affect these same pathways can change how much Orilissa ends up in your bloodstream, either making it dangerously high or reducing its effectiveness.
Orilissa can also affect other medications by altering those same pathways. So interactions go both ways — other drugs can change Orilissa levels, and Orilissa can change levels of other drugs.
These medications should not be taken with Orilissa:
If you are currently taking either of these medications, Orilissa cannot be prescribed. Your doctor will need to consider alternative treatments for your endometriosis.
St. John's Wort is a strong CYP3A4 inducer. While its specific interaction with Orilissa hasn't been extensively studied, it could potentially affect Elagolix levels similarly to Rifampin. Tell your doctor if you're taking it.
These aren't drug interactions — they're actually recommended. Because Orilissa can cause bone mineral density loss, your doctor may recommend calcium and vitamin D supplementation to support bone health during treatment.
There is no known direct interaction between Orilissa and over-the-counter pain relievers like Ibuprofen (Advil, Motrin) or Naproxen (Aleve). Many women use NSAIDs alongside Orilissa for breakthrough pain. However, always confirm with your doctor or pharmacist.
No known interaction with Orilissa. However, since Orilissa can affect liver enzymes, and Acetaminophen is also processed by the liver, your doctor may want to monitor liver function if you use Acetaminophen regularly.
Many herbal supplements can affect liver enzymes. If you take supplements regularly — especially those marketed for "hormone balance," "liver support," or "women's health" — mention them to your doctor. Some may contain phytoestrogens (plant-based estrogens) that could theoretically work against Orilissa's mechanism.
Orilissa can be taken with or without food. There are no specific food interactions listed in the prescribing information.
Grapefruit is a well-known CYP3A4 inhibitor that affects many medications. While the Orilissa prescribing information does not specifically list a grapefruit interaction, it's reasonable to be cautious with large amounts of grapefruit or grapefruit juice. Ask your pharmacist if you have concerns.
There is no specific alcohol interaction listed for Orilissa. However, since Orilissa can affect liver enzymes and alcohol is processed by the liver, moderate alcohol consumption is generally advisable. If you have any liver concerns, discuss alcohol use with your doctor.
Before your doctor prescribes Orilissa, make sure they know about:
Bring a complete list — prescription and non-prescription. Don't forget:
Your pharmacist is also an excellent resource. When you fill your Orilissa prescription, the pharmacist will check for interactions with your other medications — but they can only catch what they know about. Make sure your pharmacy has your complete medication list on file.
Orilissa has a manageable interaction profile, but a few interactions are serious. The most important ones to remember: Cyclosporine and Gemfibrozil are completely off-limits, Rifampin requires dose restrictions, and estrogen-containing birth control can reduce Orilissa's effectiveness.
When in doubt, ask your doctor or pharmacist before starting any new medication, supplement, or herbal product while on Orilissa. For more about managing your Orilissa treatment, see our guides on side effects and dosage information.
Need to find Orilissa at a pharmacy near you? Search Medfinder to check availability.
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