6 Premarin Interactions to Know About: St. John’s Wort, Grapefruit Juice, and More

It’s typical to experience annoying or frustrating symptoms during menopause. Common ones include hot flashes, night sweats, and vaginal dryness. Many women take menopausal hormone therapy (also called hormone replacement therapy) to manage these symptoms. Premarin (conjugated estrogens) is a common example that comes as an oral tablet and vaginal cream.

If you’re just starting Premarin, you likely want to know more about it. Understanding how to take it and what side effects to expect are top questions. But it’s good to be aware of potential drug interactions, too. Grapefruit juice, seizure medications, and antibiotics can all change how your body breaks down and clears Premarin. So what do you need to know about Premarin interactions?

Good to know: This article is based on drug interaction studies conducted for Premarin oral tablets. No studies have been done for Premarin Vaginal Cream. Discuss possible interactions with your healthcare team if you're using Premarin Vaginal Cream.

Premarin interactions at a glance

The following medications and foods may interact with Premarin:

• Anti-epileptics, such as carbamazepine (Tegretol) and phenobarbital

• Diltiazem (Cardizem)

• Grapefruit juice

• Macrolide antibiotics, such as erythromycin (Ery-Tab) and clarithromycin (Biaxin XL)

• Oral azole antifungals, such as ketoconazole and fluconazole (Diflucan)

• Rifampin (Rifadin)

• Ritonavir (Norvir)

• St. John’s wort

• Verapamil (Verelan)

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This isn’t a complete list. Be sure to share your medication list with your prescriber and pharmacist before starting Premarin.

Most information about Premarin interactions is based on what we know about estradiol interactions. Estradiol is a different form of estrogen from Premarin. But the body breaks down different forms of estrogen similarly. So experts assume that these interactions also pertain to Premarin.

Below, we’ll dig deeper into what you should know about six common Premarin interactions.

1. St. John’s wort

Estrogen-based medications, such as Premarin, interact with St. John’s wort, an over-the-counter supplement. St. John’s wort causes your body to clear estrogen medications faster than usual. This can make them less effective. So if you start St. John’s wort after you’ve been taking Premarin, you may notice worsened or returning menopause symptoms.

Don’t take St. John’s wort if you also take Premarin without a healthcare professional’s OK. If needed, your prescriber can help you find an alternative that doesn’t interact with Premarin.

2. Some anti-epileptic medications, such as carbamazepine

Anti-epileptics, such as carbamazepine and phenobarbital, also interact with estrogen medications, such as Premarin. These anti-epileptics may lower Premarin levels in the body. And this means Premarin might not work as well as expected.

EXPERT PICKS: WHAT TO READ NEXT

• Typical dosages: Some Premarin (conjugated estrogens) interactions are managed by changing your dose. Learn about typical and maximum Premarin dosages here.

• What to expect: Pharmacists review notable Premarin tablet side effects — from headaches to vaginal discharge — and how to manage them.

• Compare your options. Premarin is one of several available menopause treatments. Learn about the different options and how to save on them.

It’s unlikely that your prescriber would tell you to stop your anti-epileptic in order to take Premarin. In some cases, you may need to take a higher Premarin dosage. Other times, they may recommend trying a hormone-free menopause treatment instead.

3. Ritonavir

Premarin may also interact with the antiviral ritonavir. Ritonavir may lower the amount of Premarin in your body. If this happens, Premarin might not work as well for your menopause symptoms.

Keep in mind that this specific interaction hasn’t been well studied. So experts aren’t sure how greatly it could affect people who take both medications.

Your prescriber may suggest that you continue taking Premarin and ritonavir. They may ask you to let them know if your menopause symptoms don’t improve or get worse. If needed, they would likely suggest an alternative to Premarin, since ritonavir is usually taken long term to manage chronic conditions such as HIV.

Good to know: Paxlovid (nirmatrelvir / ritonavir) is a COVID-19 treatment that contains ritonavir. It shouldn’t cause significant problems if you take it with Premarin. This is because you typically only take Paxlovid for 5 days. This short treatment length is unlikely to affect how Premarin works.

4. Grapefruit juice

Grapefruit juice interacts with a lot of medications, including Premarin. But unlike the interactions listed above, this citrus fruit can raise Premarin levels in the body. This could increase your risk of Premarin side effects. Common ones include headache, breast tenderness, and stomach pain.

If you love grapefruit, discuss this Premarin interaction with your prescriber. They can let you know if there’s a safe amount of grapefruit products you can consume. If not, there are many other fruit juices, such as orange and apple juice, that don’t interact with Premarin.

5. Some macrolide antibiotics, such as erythromycin

Some macrolide antibiotics may also interact with Premarin. Examples of these antibiotics include erythromycin and clarithromycin. These medications may raise Premarin levels in the body. And this could lead to more side effects.

Most people only take antibiotics for a few days. So your prescriber may not make any adjustments to manage this Premarin interaction. Short courses of macrolide antibiotics are unlikely to cause significant problems. But your healthcare professional may also prefer to prescribe azithromycin (Zithromax, Z-Pak). This macrolide doesn’t interact with Premarin.

6. Oral azole antifungals, such as ketoconazole

Oral azole antifungals also interact with Premarin. Examples of these antifungals include ketoconazole and fluconazole. As in the examples cited above, they can raise the amount of Premarin in your body. This could mean more Premarin side effects.

In some cases, you may only take azoles for a few days. In fact, it’s common to take just a single dose of fluconazole to treat certain infections. In these cases, you may not need to do anything to manage this Premarin interaction. It’s unlikely that you’d have issues.

If you’re taking an azole for longer periods of time, your prescriber may ask you to watch for new or worsening Premarin side effects. If needed, they can lower your Premarin dosage or help you select an alternative.

Keep in mind that an interaction between topical azoles and Premarin is unlikely. Your body absorbs very little medication when you apply it to your skin. So your risk of experiencing issues is very low.

How to save on Premarin

There are ways to save on Premarin, which is available as a brand-name medication. GoodRx can help you navigate between patient assistance programs and copay savings cards to save money on your prescription:

• Save with GoodRx: Anyone with a valid prescription, regardless of insurance status, can use GoodRx to purchase Premarin at an exclusive cash price of $99 per month.

• Save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $25 per month for Premarin tablets using a savings card from the manufacturer.

• Save with a patient assistance program. If you’re uninsured or underinsured, you may be eligible for Premarin’s patient assistance program, which offers the medication free of cost.

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Written by:

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP, has over a decade of experience as a pharmacist, professor, and researcher. She was a full-time clinical professor in the pharmacy practice department at D’Youville School of Pharmacy before subsequently joining the faculty of the pharmacy practice department at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

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