What You Need to Know About Crinone Drug Interactions

Before you start using Crinone (Progesterone vaginal gel), it's important to understand how it might interact with other medications, supplements, and even over-the-counter products you're already using.

The good news is that Crinone has relatively few known drug interactions compared to many other medications. The not-so-good news is that no formal drug interaction studies have been conducted with Crinone specifically, so much of what we know is based on the pharmacology of progesterone and theoretical considerations.

Here's what you and your doctor should be aware of.

How Drug Interactions Work

A drug interaction happens when one substance changes how another substance works in your body. This can happen in several ways:

• One drug changes how another is absorbed — For vaginal medications like Crinone, other products applied vaginally can interfere with absorption
• One drug changes how another is metabolized — Some medications speed up or slow down the liver enzymes that break down progesterone
• Two drugs have overlapping effects — Taking two progestins together can amplify side effects

Because Crinone is applied vaginally rather than taken orally, it bypasses first-pass liver metabolism. This means it has fewer systemic drug interactions than oral progesterone. However, some interactions are still possible.

Medications That May Interact with Crinone

CYP3A4 Inhibitors (May Increase Progesterone Levels)

Progesterone is partially metabolized by a liver enzyme called CYP3A4. Medications that inhibit (slow down) this enzyme could theoretically increase progesterone levels in your body, potentially intensifying side effects. These medications include:

• Ketoconazole (Nizoral) — An antifungal medication
• Itraconazole (Sporanox) — Another antifungal
• Erythromycin (E-Mycin, Eryc) — An antibiotic
• Clarithromycin (Biaxin) — An antibiotic
• Ritonavir (Norvir) — An HIV medication
• Grapefruit juice — A natural CYP3A4 inhibitor (discussed in the food section below)

Because Crinone is absorbed vaginally and largely bypasses the liver, this interaction is less clinically significant than it would be for oral progesterone. However, it's still worth mentioning to your doctor.

CYP3A4 Inducers (May Decrease Progesterone Levels)

Medications that induce (speed up) CYP3A4 could theoretically decrease progesterone levels, potentially making Crinone less effective. These include:

• Rifampin (Rifadin) — An antibiotic used for tuberculosis
• Carbamazepine (Tegretol) — An anti-seizure medication
• Phenytoin (Dilantin) — An anti-seizure medication
• Phenobarbital — A barbiturate used for seizures
• St. John's Wort — An herbal supplement (discussed below)

If you are taking any of these medications, your doctor needs to know — especially if you're using Crinone for IVF or early pregnancy support, where adequate progesterone levels are critical.

Other Vaginal Products

This is perhaps the most practically important interaction to know about. The Crinone prescribing information states:

Do not use other vaginal products within 6 hours before or after applying Crinone.

Other vaginal products can interfere with how the gel adheres to the vaginal walls and how progesterone is absorbed. Products to avoid around the time of Crinone application include:

• Vaginal yeast infection treatments (Miconazole, Clotrimazole creams/suppositories)
• Vaginal moisturizers or lubricants
• Spermicides
• Vaginal douches (which should generally be avoided anyway)

If you need to use a vaginal yeast treatment while on Crinone, talk to your doctor about timing and whether an oral antifungal (like Fluconazole) would be more appropriate.

Other Progestins

Using Crinone alongside other progesterone or progestin-containing medications should be avoided unless specifically directed by your doctor. Doubling up on progestins can increase the risk of side effects like:

• Excessive drowsiness
• Bloating and breast tenderness
• Mood changes
• Blood clot risk

Other progestin products include Medroxyprogesterone (Provera), Norethindrone, and hormonal birth control.

Supplements and OTC Products to Watch

St. John's Wort

St. John's Wort is a popular herbal supplement used for depression and anxiety. It's also a potent CYP3A4 inducer, meaning it could reduce progesterone levels in your body. Avoid St. John's Wort while using Crinone, especially during fertility treatment.

Vitex (Chasteberry)

Vitex is often marketed as a natural hormone-balancing supplement. Because it may affect progesterone levels, using it alongside Crinone could complicate your treatment. Discuss this with your doctor before combining them.

Other Herbal Supplements

Many herbal supplements have not been studied for interactions with progesterone. As a general rule, tell your doctor about all supplements you're taking, including:

• Black Cohosh
• Dong Quai
• Evening Primrose Oil
• Red Clover

These are sometimes used by women for hormonal support, but their effects alongside prescription progesterone are not well understood.

Over-the-Counter Pain Relievers

Standard OTC pain relievers like Acetaminophen (Tylenol) and Ibuprofen (Advil, Motrin) are not known to interact with Crinone. However, if you're undergoing IVF or are in early pregnancy, your doctor may have specific recommendations about which pain relievers are safe. Many fertility doctors advise avoiding NSAIDs (Ibuprofen, Naproxen) around the time of embryo transfer.

Food and Drink Interactions

Because Crinone is applied vaginally and bypasses the digestive system, there are no known food interactions in the traditional sense. You don't need to take it with food, and no foods are known to interfere with its absorption.

That said, two items are worth noting:

Grapefruit and Grapefruit Juice

Grapefruit is a CYP3A4 inhibitor and could theoretically affect progesterone metabolism. The clinical significance for vaginal progesterone is likely minimal, but if you're consuming large amounts of grapefruit, mention it to your doctor.

Alcohol

There's no direct drug interaction between Crinone and alcohol. However, both progesterone and alcohol can cause drowsiness, so combining them may increase fatigue and impair alertness. If you're undergoing fertility treatment, most doctors recommend limiting or avoiding alcohol anyway.

What to Tell Your Doctor

Before starting Crinone, give your doctor a complete picture of everything you're taking:

• All prescription medications — especially seizure medications, antibiotics, antifungals, and HIV medications
• All over-the-counter medications — including pain relievers, allergy medications, and antacids
• All supplements and herbal products — especially St. John's Wort, Vitex, and any hormone-related supplements
• All vaginal products — including moisturizers, lubricants, and yeast treatments
• Your complete medical history — including liver disease, blood clot history, and current pregnancy status

Your pharmacist is also a great resource. When you fill your Crinone prescription, ask the pharmacist to check for interactions with your other medications.

Final Thoughts

Crinone has a relatively favorable drug interaction profile, largely because it's absorbed vaginally and bypasses first-pass liver metabolism. The most important practical interaction to remember is: avoid other vaginal products within 6 hours of using Crinone.

For CYP3A4 inhibitors and inducers, the clinical significance for vaginal progesterone is likely lower than for oral formulations, but it's still worth discussing with your doctor — especially if you're relying on Crinone for critical luteal phase support during IVF.

For more about this medication, check out our guides on Crinone side effects and what Crinone is and how to use it. Ready to fill your prescription? Medfinder can help you find it in stock.