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

Myfembree Drug Interactions You Need to Know About

If you're taking Myfembree (Relugolix/Estradiol/Norethindrone Acetate) for uterine fibroids or endometriosis, it's important to understand which medications, supplements, and foods can interact with it. Some interactions can make Myfembree less effective, while others can increase the risk of side effects.

This guide covers the most important Myfembree drug interactions based on FDA labeling and what you should tell your doctor before starting treatment.

How Drug Interactions Work With Myfembree

Myfembree contains three active ingredients: Relugolix, Estradiol, and Norethindrone Acetate. Drug interactions primarily affect Relugolix, the GnRH antagonist component.

Relugolix is processed in your body through two pathways:

• P-glycoprotein (P-gp) — a protein that acts like a gatekeeper, pumping drugs out of cells
• CYP3A enzymes — liver enzymes that break down many medications

Medications that affect these pathways can either increase the amount of Relugolix in your blood (raising the risk of side effects) or decrease it (making Myfembree less effective).

Major Drug Interactions: Medications to Avoid or Use With Caution

1. Oral P-glycoprotein (P-gp) Inhibitors

These medications block the P-gp pump, which means more Relugolix stays in your body than intended. This increases your exposure to the drug and may raise the risk of side effects.

Examples include:

• Cyclosporine (Sandimmune, Neoral, Gengraf) — immunosuppressant
• Erythromycin (E-Mycin, Eryc) — antibiotic
• Ketoconazole (Nizoral) — antifungal (oral form)
• Verapamil (Calan, Verelan) — blood pressure/heart medication

What to do: If you must take an oral P-gp inhibitor, take Myfembree first and wait at least 6 hours before taking the P-gp inhibitor. Your doctor may adjust your schedule or consider alternatives.

2. Combined P-gp and Strong CYP3A Inducers

These medications speed up how quickly your body eliminates Relugolix, which can make Myfembree less effective. Avoid using these with Myfembree.

Examples include:

• Rifampin (Rifadin, Rimactane) — antibiotic used for tuberculosis and other infections
• St. John's Wort — herbal supplement (discussed more below)

These are considered the most important interactions to avoid. If you need Rifampin or a similar medication, your doctor may need to consider a different treatment for your fibroids or endometriosis.

3. Hormonal Contraceptives

Myfembree should not be used together with hormonal birth control, including:

• Combined oral contraceptives ("the pill")
• Hormonal patches
• Hormonal IUDs (like Mirena or Kyleena)
• Birth control implants (like Nexplanon)
• Birth control injections (like Depo-Provera)

Why: Myfembree already contains estrogen and progestin. Adding more hormones can interfere with how Myfembree works and increase the risk of side effects. Instead, use non-hormonal contraception like condoms or a copper IUD while taking Myfembree.

Remember: Myfembree is not a contraceptive. You can still get pregnant while taking it.

4. Other Hormonal Therapies

Avoid using Myfembree with other hormonal therapies, such as:

• Hormone replacement therapy (HRT)
• Other GnRH agonists or antagonists (like Lupron Depot, Orilissa, or Oriahnn)

Using multiple hormonal medications can interfere with Myfembree's effectiveness and increase the risk of hormone-related side effects.

Supplements and Over-the-Counter Products to Watch

St. John's Wort

This is the most important supplement interaction to be aware of. St. John's Wort (Hypericum perforatum) is a popular herbal supplement used for mood support, but it is a potent P-gp and CYP3A inducer. Taking it with Myfembree can significantly reduce Relugolix levels in your blood, making your treatment less effective.

Avoid St. John's Wort completely while taking Myfembree.

Other Supplements

While there are no other major supplement interactions listed in the FDA labeling, always tell your doctor about any supplements you take, including:

• Herbal supplements (especially those that affect hormones, like black cohosh, dong quai, or red clover)
• Vitamin and mineral supplements
• Protein or fitness supplements

Some herbal supplements have weak hormonal effects that could theoretically interact with Myfembree's hormonal components.

Food and Drink Interactions

The good news: Myfembree can be taken with or without food, and there are no significant food interactions listed in the FDA labeling.

However, keep in mind:

• Grapefruit and grapefruit juice: While not specifically called out in Myfembree's labeling, grapefruit is a known CYP3A inhibitor that can affect many medications. If you regularly consume grapefruit, mention it to your doctor.
• Alcohol: There's no direct interaction listed, but alcohol can worsen side effects like dizziness, nausea, and mood changes. Moderate your intake and pay attention to how you feel.

What to Tell Your Doctor Before Starting Myfembree

Before your doctor prescribes Myfembree, make sure they know about:

All Medications You Take

This includes:

• Prescription medications (especially antibiotics, antifungals, immunosuppressants, heart medications, and seizure medications)
• Over-the-counter medications (including pain relievers, antacids, and allergy medications)
• Hormonal products of any kind

All Supplements and Herbal Products

Especially St. John's Wort, but also any other herbal or dietary supplements. Many patients don't think to mention supplements, but they can have real interactions with prescription medications.

Your Complete Medical History

Especially:

• History of blood clots, stroke, or heart attack
• Liver disease
• Osteoporosis or low bone density
• History of depression or mood disorders
• Diabetes or high cholesterol

Any Planned Surgeries or Procedures

If you're planning surgery, your doctor may want to temporarily stop Myfembree, as the estrogen component can increase the risk of blood clots during and after surgery.

Final Thoughts

Myfembree has a manageable interaction profile, but the key interactions — P-gp inhibitors, CYP3A inducers like Rifampin, St. John's Wort, and hormonal contraceptives — are important to know about. The simplest way to stay safe is to give your doctor a complete list of everything you take before starting treatment.

For more information about Myfembree, see our guides on what Myfembree is, side effects to watch for, and how to save money on your prescription. When you're ready to fill it, use Medfinder to find a pharmacy with Myfembree in stock near you.