Skip to main content
Drug Info

Fluoxetine interactions to avoid

Fluoxetine can interact with prescription medications used for pain, seizures, infections, and other behavioral disorders
Kristi Torres writer headshot
By | Jan. 18, 2024
Rx capsules: Fluoxetine interactions to avoid

Key takeaways

  • MAOI drugs are contraindicated and should not be combined with fluoxetine. These include selegiline, phenelzine, isocarboxazid, and tranylcypromine.

  • Taking fluoxetine with certain drugs can cause a person to bleed more easily. These include blood thinners like warfarin or NSAIDs such as aspirin and ibuprofen.

  • Taking fluoxetine with muscle relaxers, seizure medications, or pain medications can increase the chance of drowsiness and make it dangerous to drive.

  • Taking fluoxetine with other central nervous system drugs can increase the chance of serotonin syndrome or exacerbate the nervous system side effects. This includes other antidepressants, seizure drugs such as carbamazepine or phenytoin, as well as benzodiazepines such as alprazolam or diazepam.

  • If one suspects they are experiencing a drug reaction or any other adverse effects of fluoxetine, they should consult a prescriber immediately. If an allergic reaction (hives, swelling of the face, tongue, and mouth) occurs, one should stop fluoxetine use immediately and seek medical help.

In this article:

Fluoxetine, the generic for Prozac, is a selective serotonin reuptake inhibitor (SSRI) approved by the U.S. Food and Drug Administration (FDA) and used primarily in treating major depressive disorder. Fluoxetine may also be prescribed to help treat mental health conditions such as obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), or bulimia nervosa. Fluoxetine may also be found under the brand name Sarafem. Fluoxetine interacts with several medications; some interactions are more severe than others. Fluoxetine does not combine with monoamine oxidase inhibitors (MAOIs) such as selegiline and phenelzine. The psychoactive drugs pimozide and thioridazine should be avoided while taking fluoxetine. Patients should be completely off MAOIs for 14 days before starting fluoxetine therapy or stop fluoxetine therapy at least 5 days before starting an MAOI. Other drugs will affect fluoxetine as the body processes it and how it works, including common antibiotics, pain medications, and seizure medications. Before starting fluoxetine therapy, ensure that the prescriber and pharmacist know all drugs and supplements, including over-the-counter (OTC) choices. These medical professionals can help in avoiding drug interactions. 

Fluoxetine drug interactions

Fluoxetine interacts with a variety of different drug types. It can interact with prescription medications used for pain, seizures, infections, and other behavioral disorders. It can also interact with OTC pain relievers and supplements. Below are some of the most common classes of drugs that interact with fluoxetine. This list is not intended to be all-inclusive, and one should always seek medical advice from a healthcare professional with any questions about interactions.

Monoamine oxidase inhibitors (MAOIs)

MAO inhibition reduces the metabolism of serotonin. SSRIs like fluoxetine block the reuptake of serotonin in the brain. MAOIs like selegiline, when taken with fluoxetine, would result in the combined effect of slowing the metabolism of existing serotonin along with blockade, making more serotonin available, and this could result in serotonin syndrome, a type of serotonin toxicity. Serotonin syndrome is not common, but when it does occur, it results in agitation, confusion, nausea, insomnia, and diarrhea. Muscle rigidity and tremors can also occur. While studies have shown that this may not occur at low doses of each drug when combined, the threshold for every patient can be different. Therefore, the combination of MAOIs and fluoxetine is prohibited. Most prescribers will avoid MAOI prescribing due to their interactions with many drug classes, not just SSRIs. Most prescribers will continue SSRI therapy and look for an alternative to an MAOI, such as a tricyclic antidepressant (TCA) like Elavil (amitriptyline) or a selective norepinephrine reuptake inhibitor (SNRI) such as Cymbalta (duloxetine) and Effexor (venlafaxine).

Examples: Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), Parnate (tranylcypromine)

First generation antipsychotics

The use of certain antipsychotic medications is prohibited with fluoxetine and could be life-threatening. Fluoxetine inhibits the enzymes responsible for the metabolism of these antipsychotics. These antipsychotics, as well as SSRIs, carry the risk of QT prolongation. This is an abnormal rhythm of the heart, and this risk is compounded when these drugs are taken together. The combination can lead to QT prolongation, ventricular arrhythmias, and even death. For patients needing a combination treatment with an antipsychotic and antidepressant, prescribers can prescribe atypical antipsychotics, which were developed more recently and have fewer interactions and serious side effects. 

Examples: Orap (pimozide), Mellaril (thioridazine), Nardil (phenelzine), Haldol (haloperidol)

Antibiotics

Linezolid is an antibiotic that also happens to be an inhibitor of MAO. Therefore, the concurrent use of fluoxetine is contraindicated due to the risk of serotonin syndrome, as described above. If linezolid treatment is urgent and necessary, discontinue fluoxetine immediately. The patient should be monitored for signs of serotonin syndrome for up to 5 weeks. If the patient experiences a psychiatric crisis while on linezolid, an alternative medication to fluoxetine that is not actioned through serotonin should be used.

Examples: Zyvox (linezolid)

Antifungals

Certain antifungal medications are contraindicated with fluoxetine. There is an increased risk of QT prolongation and torsade de pointes (TdP) with these antifungal drugs, and that risk is worsened when taken with fluoxetine. These abnormalities of the heart’s rhythm can be fatal, and this combination should be avoided if at all possible. 

Examples: Nizoral (ketoconazole)

Other SSRIs

The use of two SSRIs combined carries the risk of serotonin syndrome due to two serotonergic drugs used concomitantly. Having two medications simultaneously block the reuptake of serotonin can lead to too much free serotonin. Medical professionals do not recommend the combined use of two SSRIs.

Examples: Celexa (citalopram), Lexapro (escitalopram), Zoloft (sertraline), Paxil (paroxetine)

Opiate pain relievers

Opiate pain relievers carry a risk for adverse events such as dizziness and drowsiness, and these can be compounded by these effects, which can occur with fluoxetine as well. The use of these drugs with fluoxetine also carried the risk of serotonin syndrome because opioid medications have serotonergic activity as well. The opiate response of some medications may be exaggerated. Patients should be monitored for signs of an exaggerated opiate response. These include sedation, dizziness, nausea, constipation, and respiratory depression.

Examples: Dilaudid (hydromorphone), Duragesic (fentanyl), Opana (oxymorphone), Ultram (tramadol), Codeine

Blood thinning medications

Fluoxetine inhibits enzymes that metabolize certain drugs that cause blood thinning. Warfarin, a prescription blood thinner, can cause more blood thinning than is desired when taken with fluoxetine, making one more vulnerable to bleeding. Doctors should perform blood tests regularly to monitor for this blood-thinning effect, and if necessary, warfarin dose adjustments may need to be made. This effect can also occur between nonsteroidal anti-inflammatory drugs (NSAIDs) and fluoxetine as well.

Examples: Coumadin (warfarin), Advil (ibuprofen), Aspirin

Fluoxetine food interactions

There are no known effects of food on the activity of fluoxetine. Therefore, one can take fluoxetine with any food.

There is some data to suggest that certain food choices are linked to higher rates of depression. Lower consumption of fruits and vegetables, as well as dairy, may be linked to higher rates of depression. Conversely, higher rates of meat consumption may also be associated with depression. There is also evidence that junk food and fast food consumption are associated with depression. These suggestions reemphasize the importance of lifestyle and behavioral changes in addition to medication to treat depression and improve quality of life. 

RELATED: The best diet to fight depression

Other fluoxetine interactions

Fluoxetine interactions are not limited to just medications. Alcohol consumption can affect the success of fluoxetine treatment as well as some dietary supplements.

Fluoxetine and alcohol 

Alcohol consumption can worsen fluoxetine’s adverse effects on the nervous system. Side effects such as dizziness, drowsiness, and difficulty concentrating may be worse when combining alcohol with fluoxetine. If these agents are combined, even occasionally, one should not drive. Alcohol consumption may also affect a person’s depressive disorder directly. The combination should be avoided if at all possible.

Fluoxetine and caffeine 

Caffeine does not interact with fluoxetine. There is some thought that caffeine has a positive effect on mood, and therefore, its relationship with fluoxetine could be beneficial.

Fluoxetine and disease/CBD/illicit drugs/vitamins/herbal supplements/etc.

St. John’s Wort is a supplement that may have some efficacy in treating depression. Its mechanism is serotonergic like the SSRIs, so the combination of this supplement with drugs like fluoxetine can leave the patient at risk for serotonin syndrome. Do not take St. John’s Work and any SSRI together.

How to minimize fluoxetine interactions

Speak to a doctor or pharmacist about the medications being taken before starting fluoxetine to avoid interactions with it. If one is currently on fluoxetine and starting any other new medication, ensure the prescriber knows. Be sure to pay close attention to other drugs prescribed for mood or behavior, as well as some pain medications and antibiotics.

When to talk to a healthcare provider about fluoxetine interactions

If experiencing symptoms that could be serotonin syndrome, contact a healthcare professional immediately. These may include confusion, changes in blood pressure, increased heart rate, sweating, shaking, nausea, and vomiting. If depression or other mood symptoms get worse while taking fluoxetine, one should also let a doctor know. Anytime a new drug is added to a medication regimen, notify all healthcare professionals on your care team.