Addyi Drug Interactions Are Serious — Here's Your Complete Guide

If there's one thing you need to understand before starting Addyi (Flibanserin), it's this: drug interactions with this medication aren't just theoretical warnings on a label. They can cause dangerous drops in blood pressure and fainting.

Addyi carries an FDA boxed warning specifically about interactions with alcohol and certain medications. Knowing what to avoid — and making sure your doctor knows everything you take — is essential for using Addyi safely.

How Drug Interactions Work with Addyi

Your liver breaks down Addyi using an enzyme system called CYP3A4 (and to a lesser extent, CYP2C19). When other substances block or slow down these enzymes, Flibanserin builds up in your bloodstream to higher-than-intended levels. Higher levels mean stronger side effects — particularly the dangerous ones like severely low blood pressure and fainting.

This is why the interaction list is so specific. It's not about vague concerns — it's about measurable, documented increases in Flibanserin blood levels that directly increase risk.

Medications That Interact with Addyi

Contraindicated — Do Not Take Together

These are absolute no-go combinations. Addyi should not be used with any of the following moderate or strong CYP3A4 inhibitors:

• Antifungals: Ketoconazole, Itraconazole, Fluconazole (Diflucan) — commonly prescribed for yeast infections
• Antibiotics: Clarithromycin, Erythromycin, Ciprofloxacin
• HIV medications: Protease inhibitors (Ritonavir, Nelfinavir, and others)
• Heart/blood pressure medications: Diltiazem, Verapamil
• Antidepressants: Nefazodone
• Other: Conivaptan

If you currently take any of these medications, you cannot take Addyi. Your doctor will need to either find an alternative to the interacting medication or consider a different treatment for HSDD.

A particularly important note: Fluconazole (Diflucan) is one of the most commonly prescribed medications for vaginal yeast infections. If you're taking Addyi and develop a yeast infection, tell your doctor — they'll need to prescribe a non-oral antifungal or a different antifungal that doesn't inhibit CYP3A4.

Use with Caution — Monitor Closely

These medications may increase Flibanserin levels, but the interaction is less severe. Your doctor should weigh the risks:

• Weak CYP3A4 inhibitors: Cimetidine (Tagamet), Ginkgo biloba, Resveratrol supplements
• CYP2C19 inhibitors: Certain benzodiazepines, proton pump inhibitors (PPIs like Omeprazole), and some SSRIs
• P-glycoprotein substrates with narrow therapeutic index: Digoxin (Addyi may increase Digoxin levels, requiring dose monitoring)

CNS Depressants — Increased Sedation Risk

Medications that cause drowsiness can amplify Addyi's sedating effects, increasing the risk of severe sleepiness, low blood pressure, and fainting:

• Benzodiazepines: Alprazolam (Xanax), Lorazepam (Ativan), Diazepam (Valium)
• Opioid pain medications: Hydrocodone, Oxycodone, Tramadol
• Antihistamines: Diphenhydramine (Benadryl), Doxylamine (found in NyQuil and sleep aids)
• Sleep medications: Zolpidem (Ambien), Eszopiclone (Lunesta)

If you take any of these regularly, your doctor needs to know before prescribing Addyi.

Supplements and Over-the-Counter Products

Don't assume that "natural" means safe with Addyi. Several common supplements interact:

• Ginkgo biloba: A weak CYP3A4 inhibitor that can increase Flibanserin levels
• Resveratrol: Found in red wine supplements, also a CYP3A4 inhibitor
• St. John's Wort: A CYP3A4 inducer — may reduce Addyi's effectiveness rather than increase toxicity, but still disrupts the medication's intended effect
• Diphenhydramine (Benadryl): Available over the counter, this antihistamine is a CNS depressant that can amplify Addyi's sedating effects
• Melatonin and other sleep aids: May compound drowsiness when taken alongside Addyi at bedtime

Always bring a complete list of supplements to your doctor's appointment — not just prescriptions.

Food and Drink Interactions

Alcohol — The Most Dangerous Interaction

Alcohol is the most important interaction to understand. Addyi's boxed warning centers on this risk.

When you combine Addyi with alcohol, blood pressure can drop to dangerously low levels, causing severe dizziness, fainting, and potential injury from falls. This isn't a rare side effect — it's a well-documented, dose-dependent risk.

The rules:

• After 1–2 alcoholic drinks: Wait at least 2 hours before taking Addyi
• After 3 or more drinks: Skip your Addyi dose entirely that night
• Many doctors recommend avoiding alcohol altogether while on Addyi

For more on how to manage this and other side effects, see our guide on Addyi side effects.

Grapefruit and Grapefruit Juice

Grapefruit is a well-known CYP3A4 inhibitor. Drinking grapefruit juice or eating grapefruit while taking Addyi can increase Flibanserin levels in your blood, raising the risk of side effects. Avoid grapefruit products while on Addyi.

What to Tell Your Doctor Before Starting Addyi

Before your first dose of Addyi, make sure your prescriber knows:

1. Every prescription medication you take — even ones prescribed by other doctors
2. All over-the-counter medications — especially antihistamines, sleep aids, and pain relievers
3. All supplements and herbal products — including Ginkgo, Resveratrol, St. John's Wort, and melatonin
4. Your alcohol habits — be honest about how often and how much you drink. Your doctor needs this information to keep you safe
5. Any liver problems — Addyi is contraindicated in hepatic impairment because the liver is responsible for metabolizing Flibanserin
6. If you're pregnant, planning to become pregnant, or breastfeeding — Addyi has not been studied in these populations

If anything changes after you start Addyi — a new prescription, a new supplement, even a short course of antibiotics — tell your doctor or pharmacist before taking it alongside Addyi.

Final Thoughts

Addyi's drug interactions are manageable, but only if you know about them. The most important takeaways: avoid alcohol or follow the strict timing rules, never combine with moderate or strong CYP3A4 inhibitors, and give your doctor a complete picture of everything you take.

For a full overview of the medication, read What Is Addyi?. When you're ready to fill your prescription, use Medfinder to find a pharmacy with Addyi in stock.