7 Fluoxetine Interactions to Watch Out for

Fluoxetine (Prozac) is an antidepressant that treats mental health conditions like depression and anxiety. It’s a selective serotonin reuptake inhibitor (SSRI) that has been around for a long time. In fact, it was the first SSRI approved in the U.S. But it continues to be a popular treatment option. As of 2020, it was in the top 25 medications prescribed in the country.

Taking fluoxetine has its risks, including side effects and interactions. While some of these interactions are mild, others can be severe. Interactions may worsen the side effects of fluoxetine or other medications or cause other symptoms.

Below, we’ll review seven fluoxetine interactions you should know about. But keep in mind that this isn’t a comprehensive list. Review your current medication list with your healthcare provider and pharmacist. They can help you avoid potentially dangerous combinations.

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1. Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) treat conditions like Parkinson’s disease and depression. They aren’t prescribed very often because they have many side effects and interactions. They also require you to follow a strict diet to avoid complications. Examples of MAOIs include phenelzine (Nardil) and selegiline (Zelapar, Emsam).

Fluoxetine and MAOIs both raise levels of serotonin in the brain. Taking them together can lead to dangerously high levels. In rare cases, too much serotonin can cause serotonin syndrome.

Serotonin syndrome is a potentially life-threatening condition that causes symptoms ranging from mild to severe. Mild symptoms are more common and may include tremors, a fast heartbeat, and sweating. Severe symptoms include high fever, agitation, andrigid muscles. Even if you have mild symptoms, you should contact your healthcare provider to discuss next steps.

Fluoxetine and MAOIs shouldn’t be taken together. If you’re switching from an MAOI to fluoxetine, you should wait at least 14 days (2 weeks) after you stop taking the MAOI to start taking fluoxetine. If you’ve been taking fluoxetine, you’ll need to not be taking it for at least 5 weeks before you start taking an MAOI.

2. Other medications that raise serotonin levels

There are many medications other than MAOIs that raise serotonin levels. These are called serotonergic medications. Taking fluoxetine with any of these medications raises your risk for serotonin syndrome. But the risk is typically lower than it is when combining fluoxetine with MAOIs.

Examples of serotonergic medications are:

• Tricyclic antidepressants (TCAs) like amitriptyline

• Triptan migraine medications like sumatriptan (Imitrex)

• Lithium (Lithobid)

• Certain opioids like tramadol (Ultram, ConZip)

• Other SSRIs like escitalopram (Lexapro)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs) like duloxetine (Cymbalta)

If you’re taking one of these types of medications, check with your healthcare provider before you start taking fluoxetine. They may suggest watching for symptoms of serotonin syndrome if you need to take both. Or they may recommend an alternative medication.

3. St. John’s wort

You may have heard of St. John’s wort being used as a natural remedy for depression. While this herbal supplement is derived from a natural source, it still has side effects and interactions. Raising serotonin levels is part of how St. John’s wort works. So taking it with fluoxetine raises your risk for serotonin syndrome.

Let your healthcare provider know if you’re taking St. John’s wort. (Since you can buy it over the counter, they may not know that you’re taking it.) Typically, you shouldn’t combine St. John’s wort and fluoxetine. Your healthcare provider may recommend changing one of these medications to avoid an interaction.

4. Medications that raise the risk of bleeding

Certain medications can raise your risk of bleeding. One common example is blood thinners, which include antiplatelets ans anticoagulants. These medications prevent unwanted blood clots. But they also come with a higher risk of bleeding because of their blood-thinning effects. SSRIs like fluoxetine also slightly raise your risk of bleeding. So taking blood thinners with fluoxetine increases bleeding risks even more.

Examples of blood thinners include:

• Warfarin (Coumadin, Jantoven)

• Apixaban (Eliquis)

• Rivaroxaban (Xarelto)

• Clopidogrel (Plavix)

• Prasugrel (Effient)

Combining fluoxetine with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can also increase your risk of bleeding. Most NSAIDs aren’t considered blood thinners. But they can make bleeding more likely, primarily in the gut.

Some people may not be able to avoid combining fluoxetine with these medications. If this is the case for you, your healthcare provider may ask you to watch for signs of bleeding. Mild symptoms include bruising easily, bleeding gums, and nosebleeds. More serious symptoms include red stool or black stool, unexplained stomach pain, and blood in vomit. Be sure to report any signs of bleeding to your healthcare provider — even if they seem mild.

5. Pimozide and thioridazine

Pimozide and thioridazine are in a class of medication called typical antipsychotics. Both are typically taken only when other treatments haven’t worked. This is because these medications have many side effects.

Fluoxetine blocks the effects of the liver enzyme (protein) that helps break down pimozide and thioridazine. When combined with fluoxetine, these antipsychotics can reach dangerously high levels in the body. And this raises the risk of serious side effects.

Also, pimozide, thioridazine, and fluoxetine can all prolong (lengthen) the QT interval. The QT interval is the resting time that occurs between heart beats. If the QT interval is longer than usual, it can cause potentially life-threatening arrhythmias (abnormal heart rhythms). Symptoms of abnormal heart rhythms include fainting, dizziness, and palpitations.

The risk of developing serious arrhythmias rises greatly when fluoxetine is taken with pimozide or thioridazine. For this reason, you should avoid the combination.

6. Medications metabolized by certain liver enzymes

There are medications other than pimozide and thioridazine that are broken down by the enzyme that fluoxetine blocks. And fluoxetine can also lead to elevated levels of these medications. The possible effects typically aren’t as severe as when combining the SSRI with pimozide or thioridazine. But you may need dosage changes to help limit side effects.

Examples of these medications include:

• Flecainide

• Propafenone (Rythmol)

• TCAs like imipramine (Tofranil)

• Benzodiazepines like alprazolam (Xanax)

• Antipsychotics like risperidone (Risperdal)

• Seizure control medications, such as phenytoin (Dilantin, Phenytek) and carbamazepine (Tegretol)

If you’re taking medications that could interact with fluoxetine in this way, your healthcare provider may suggest a lower dose of these other medications. Be sure to let them know if you notice any new or worsening side effects, especially after a fluoxetine dose change.

7. Medications that affect heart rhythm

As mentioned earlier, fluoxetine can prolong the QT interval. In addition to pimozide and thioridazine, other medications can also have this effect. Combining fluoxetine with these medications can raise the risk of abnormal heart rhythms.

Other medications that prolong the QT interval include:

• Antiarrhythmic medications, such as amiodarone (Pacerone) and sotalol (Betapace)

• Certain antibiotics, such as ciprofloxacin (Cipro) ans azithromycin (Zithromax)

• Certain antifungal medications like fluconazole (Diflucan)

• Antipsychotics, such as haloperidol (Haldol) and ziprasidone (Geodon)

• Opioids like methadone (Methadose)

Ideally, it’s best to avoid taking these medications with fluoxetine. Your healthcare provider may recommend an alternative to fluoxetine to avoid this interaction. But there may be times when the benefits of combining medications outweigh the risks. In this case, your provider will likely monitor your heart rhythm at checkups.

When should I contact my healthcare provider about a fluoxetine interaction?

The best way to avoid interactions is by talking with your healthcare provider before you start taking fluoxetine. Make sure to show them your current medication list. This can help them screen for interactions and determine whether it’s safe for you to take fluoxetine with your other medications.

If you suspect a possible interaction after you’ve started taking fluoxetine, let your healthcare provider and pharmacist know. They’re likely already aware and may have made adjustments to account for it. But it doesn’t hurt to double-check.

Unusual symptoms, like red or black stools, heart palpitations, or severe agitation, could be signs of an interaction. Let your healthcare provider know right away if you have any of these.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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