What Can Interact With Endometrin — and Why It Matters

When you're going through fertility treatment, the medications you take need to work exactly as intended. Endometrin (Progesterone vaginal insert) is a key part of many IVF protocols, and certain other medications, supplements, and even vaginal products can interfere with how it's absorbed or how well it works.

This guide covers the known Endometrin drug interactions, what to watch out for, and what to tell your doctor before you start treatment.

How Drug Interactions Work With Endometrin

Endometrin contains micronized Progesterone, which is absorbed through the vaginal tissue directly into the uterus. Because it bypasses the digestive system, Endometrin has fewer drug interactions than oral Progesterone. However, interactions can still happen in two main ways:

1. Metabolic interactions: Progesterone is metabolized in the body by an enzyme called CYP3A4. Medications that speed up or slow down this enzyme can change how much Progesterone stays active in your system.
2. Local absorption interference: Other vaginal products can physically interfere with how Endometrin dissolves and is absorbed in the vagina.

Medications That May Interact With Endometrin

Major Interactions: CYP3A4 Inducers (May Decrease Progesterone Levels)

These medications can speed up the breakdown of Progesterone, potentially lowering its levels in your body:

• Rifampin (Rifadin) — An antibiotic used for tuberculosis and other infections. This is one of the strongest CYP3A4 inducers.
• Carbamazepine (Tegretol) — An anticonvulsant used for epilepsy and nerve pain.
• Phenytoin (Dilantin) — Another anticonvulsant that can significantly reduce Progesterone levels.

If you take any of these medications, your fertility doctor needs to know. They may need to adjust your Endometrin dose or monitor your Progesterone levels more closely.

Moderate Interactions: CYP3A4 Inhibitors (May Increase Progesterone Levels)

These medications can slow down Progesterone metabolism, potentially raising levels higher than intended:

• Ketoconazole (Nizoral) — An antifungal medication. Note: do not use vaginal antifungal products while using Endometrin (more on this below).
• Other strong CYP3A4 inhibitors — Including Itraconazole (Sporanox), Clarithromycin (Biaxin), and certain HIV medications like Ritonavir (Norvir).

While higher Progesterone levels may not always be harmful, your doctor should be aware so they can monitor appropriately.

Other Progestins

Using Endometrin alongside other Progesterone or progestin-containing medications could lead to excessive Progesterone exposure. Make sure your doctor knows if you're taking any other form of Progesterone, including:

• Prometrium (oral Progesterone)
• Progesterone in oil injections
• Crinone (Progesterone vaginal gel)
• Progestin-containing birth control (if recently discontinued)

Vaginal Products to Avoid

This is one of the most important — and most overlooked — interactions with Endometrin. Do not use other vaginal products at the same time as Endometrin. These can physically interfere with how the insert dissolves and how Progesterone is absorbed.

Products to avoid include:

• Vaginal antifungal creams or suppositories (such as Miconazole or Clotrimazole)
• Spermicides
• Vaginal moisturizers or lubricants (unless your doctor specifically approves a particular product)
• Vaginal douches

If you develop a vaginal yeast infection during treatment, tell your fertility clinic before using any antifungal product. They may recommend an oral antifungal instead, or time the vaginal product to minimize interference with Endometrin.

Supplements and OTC Products to Watch

Most common supplements don't interact significantly with Endometrin, but there are a few worth mentioning:

• St. John's Wort — This herbal supplement is a known CYP3A4 inducer and could lower Progesterone levels. Avoid it during fertility treatment.
• Herbal supplements with estrogenic or hormonal activity — Products like black cohosh, red clover, and dong quai may have hormonal effects. Discuss any herbal supplements with your doctor before combining them with Endometrin.
• High-dose Vitamin E — In very high doses, Vitamin E may have mild effects on hormonal metabolism. Standard prenatal vitamin doses are fine.

As a general rule, tell your fertility doctor about every supplement you take — even if it seems harmless.

Food and Drink Interactions

Good news here: because Endometrin is delivered vaginally rather than orally, there are no significant food or drink interactions. You don't need to worry about timing it around meals, and foods like grapefruit (which can affect oral medications metabolized by CYP3A4) are not a concern with vaginal Endometrin.

That said, general fertility treatment recommendations still apply — moderate caffeine intake, limit alcohol, and eat a balanced diet.

What to Tell Your Doctor Before Starting Endometrin

Before you begin Endometrin, give your fertility doctor a complete list of:

• All prescription medications you currently take
• Over-the-counter medications including pain relievers, antihistamines, and antacids
• Vitamins and supplements including prenatal vitamins, herbal products, and any fertility supplements
• Vaginal products you use or have recently used
• Any recent medication changes — even stopping a medication can affect your treatment

Your doctor can check for interactions and adjust your treatment plan if needed. Don't assume something is too minor to mention — when it comes to fertility treatment, every detail matters.

Final Thoughts

Endometrin has relatively few drug interactions compared to oral medications, thanks to its vaginal delivery route. The most important things to remember are: avoid vaginal products that could interfere with absorption, tell your doctor about any CYP3A4 inducers or inhibitors you take, and skip St. John's Wort during treatment.

For more on how Endometrin works and what to expect, see our guides on how Endometrin works and Endometrin side effects. And if you need help finding Endometrin at a pharmacy, Medfinder can show you where it's in stock near you.