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As is the case with any other medication, Prozac interactions can occur when combined with other drugs and food. In fact, people with certain diseases or other medical conditions may not be able to take this medication, either. In such instances, patients will need to find a viable alternative for Prozac (fluoxetine hydrochloride) or have a medical provider adjust their dose accordingly.

Drug Interactions

The U.S. National Library of Medicine states that the following drugs may interact with Prozac.

  • Monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil) and tranylcypromine (Parnate)
  • Linezolid (Zyvox)
  • Intravenous (IV) methylene blue (ProvayBlue)
  • Pimozide (Orap)
  • Thioridazine
  • CNS-acting drugs, or drugs that affect the central nervous system
  • Serotonergic drugs, or drugs that affect levels of serotonin
  • Drugs that interfere with hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin (Jantoven), and aspirin
  • “Drugs tightly bound to plasma proteins”
  • Drugs metabolized by the enzyme (specialized protein) CYP2D6 or CYP2C19
  • Tricyclic antidepressants (TCAs), such as amitriptyline (Elavil) and doxepin (Silenor, Zonalon, Prudoxin)
  • Benzodiazepines (“benzos”), such as diazepam (Valium) and alprazolam (Xanax)
  • Antipsychotics (neuroleptics) like aripiprazole (Abilify)
  • Anticonvulsants (anti-seizure or anti-epileptic medications), such as gabapentin (Neuraptine)
  • Lithium
  • “Drugs that prolong the QT interval”

These drugs may either be completely contraindicated (recommended against) in combination use with Prozac or they may require dosage adjustments. Please note that this list may not be complete; other interactions not listed here may occur. 

Zoloft (Sertraline)

Zoloft (sertraline) belongs to the same class of antidepressants as Prozac; that is, they are both selective serotonin reuptake inhibitors (SSRIs). Combined use of these antidepressants elevates risk of the potentially lethal condition serotonin syndrome (SS).

Signs of SS include:

Anyone who suspects they have serotonin syndrome should seek emergency medical attention right away.

For information on what the difference between these two drugs is, please visit our Prozac vs Zoloft page.


Adderall is effectively a mix of amphetamines that can treat conditions like ADHD (attention deficit hyperactivity disorder). Mixing Adderall and Prozac increases risk of SS.

Cold Medicine

Many over-the-counter (OTC) medications contain ingredients that can negatively interact with fluoxetine. NyQuil, for instance, contains dextromethorphan (DMX). Experts have reported that, in rare cases, use of NyQuil simultaneously with an SSRI (the drug class to which Prozac belongs) increases the risk of serotonin syndrome (SS). Other research suggests that this risk is only present when taking an excessive amount of DMX-containing medicine.

Given such risk, patients should consult with their medical provider before taking NyQuil or other cold medicine with Prozac.

Olanzapine (Zyprexa)

Zyprexa (olanzapine) is an atypical antipsychotic drug. The FDA states that it is approved to treat/can be used in the treatment of schizophrenia, bipolar I disorder, and treatment-resistant depression. The enzyme (specialized protein) CYP2D6 plays a small role in metabolizing olanzapine. The U.S. National Library of Medicine advises caution when combining Prozac with drugs metabolized by CYP2D6. Typically, dose adjustment is necessary with combination therapy.

Ibuprofen (Advil)

Ibuprofen is a non-steroidal anti-inflammatory drug, or NSAID. Among other uses, NSAIDs can prevent blood clotting. Taken together with Prozac, they can increase the risk of bleeding, especially upper GI bleeding.

Wellbutrin (Bupropion)

Wellbutrin (bupropion) is a popular antidepressant that, when used with fluoxetine, increases SS risk. However, medical providers may sometimes recommend patients use these two medications together if they believe the benefits outweigh the potential risks.

Vyvanse (Lisdexamfetamine)

Vyvanse (lisdexamfetamine) is an amphetamine derivative, meaning that it functions as a stimulant. Patients use it to help treat ADHD and other conditions. According to the FDA, combination therapy with Vyvanse and Prozac can result in interactions. In fact, experts have stated that Prozac can have “clinically important interactions with amphetamines” resulting in SS.

Food Interactions

Fortunately, most food and drink do not affect Prozac’s bioavailability, which means patients can usually take this medication with or without food.

Prozac and Alcohol

For more information, please visit our page on Prozac and alcohol interactions.

Herbs & Herbal Supplements        

Patients should not use Prozac with St. John’s wort (Hypericum perforatum), as negative interactions can occur.


Patients should always clear any vitamins—even over-the-counter ones—with their medical provider before using them in combination with Prozac.

Disease & Conditions Interactions

Everybody is different, which means sometimes certain groups of people will either have to avoid taking this medication or adjust its typical usage in order to avoid adverse reactions. According to the U.S. National Library of Medicine, those groups include the following:

  • Pregnant individuals
  • Lactating individuals
  • Patients with hepatic (liver) impairment

Please note that this list may not be complete, and there may be other diseases and medical conditions where patients should not take this medication.

Prozac and Pregnancy

For more information, please visit our page on Prozac and pregnancy risks.

Prozac and Breastfeeding

For more information, please visit our page on Prozac and pregnancy risks.

Other Interactions

Other potential interactions may occur with the following.

Electroconvulsive Therapy (ECT)

The U.S. National Library of Medicine reports that, rarely, medical providers have noted prolonged seizures in people who received treatment that included both Prozac and ECT.

Disclaimer: this article does not constitute or replace medical advice. If you have an emergency or a serious medical question, please contact a medical professional or call 911 immediately. To see our full medical disclaimer, visit our Terms of Use page.

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