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Fluoxetine interactions can occur with other medications and even food. In some cases, patients with certain medical conditions will also have to avoid taking fluoxetine (Prozac) in order to avoid negative interactions.

Drug Interactions

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

  • 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
  • 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 fluoxetine or they may require dosage adjustments. Please note that this list may not be complete; other interactions not listed here may occur. 


Adderall is a medication that can treat conditions like ADHD. Mixing Adderall and fluoxetine can increase the risk of the potentially life-threatening condition known as serotonin syndrome (SS). Signs of SS include:

  • Agitation
  • Confusion
  • Nausea, Vomiting, Diarrhea
  • Excessive sweating
  • Hypertension (high blood pressure)
  • Muscle incoordination
  • Pupil dilation
  • Rigid muscles
  • Tachycardia (fast heart beat)

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


Aspirin has many uses, including reducing pain and fever as well as preventing blood clots. Since aspirin affects hemostasis (preventing blood clots or “thinning the blood”), people who use fluoxetine are at an increased risk of bleeding, particularly upper GI bleeding.

NyQuil and Other Cold Medicine

NyQuil is a popular over-the-counter (OTC) cold medicine that contains the active ingredients acetaminophen, dextromethorphan (DMX), and doxylamine. Experts have reported that, in rare cases, use of NyQuil simultaneously with a selective serotonin reuptake inhibitor (SSRI, the drug class to which fluoxetine belongs) increases the risk of serotonin syndrome (SS). However, other research suggests that such risk is only present when taking an excessive amount of DMX-containing medicine.

SS can be fatal and occurs when an excessive amount of the neurotransmitter serotonin floods the central nervous system. Given such risk, patients should consult with their medical provider before taking NyQuil and other cold medicines with fluoxetine.

Claritin (Loratadine)

Loratadine (Claritin) is a popular OTC antihistamine, or allergy medication. According to DrugBank, combining loratadine and fluoxetine may possibly increase the risk of psychomotor impairment.


Melatonin is a hormone the body produces naturally. While most people know that melatonin plays a large role in regulating the sleep-wake cycle, fewer know that serotonin is the precursor to melatonin. In other words, the body needs serotonin to produce melatonin.

Limited research suggests that combined use of melatonin and fluoxetine could lead to beneficial results. For example, one 2009 Clinical Pharmacology study found that long-term use of fluoxetine in rats resulted in higher levels of melatonin during the day. While researchers admit that the full effects of this increase are not fully clear, they believe one such side effect could be increased sleep quality. Notably, sleep and mood disorders like depression are closely linked; experts have correlated boosts in sleep quality with subsequent improvements in depression.

Another 2017 Neuroscience Bulletin article reached similar results. This study focused on male mice and found that combination use resulted in a synergistic effect. Simply put, using both fluoxetine and melatonin resulted in a boost of the antidepressant effects of both substances.

Olanzapine (Zyprexa)

Zyprexa (olanzapine) is an antipsychotic drug; the enzyme CYP1A2 primarily metabolizes this drug, although CYP2D6 plays a smaller role in olanzapine metabolism. The U.S. National Library of Medicine advises caution when combining fluoxetine with drugs metabolized by CYP2D6. Typically, dose adjustment of olanzapine is required when using combination therapy.

Trazodone (Desyrel)

Trazodone is both a sedative and antidepressant medicine that experts believe works partly by inhibiting the reuptake (reabsorption) of serotonin. Since trazodone affects serotonin, there is an increased risk of the potentially fatal condition known as serotonin syndrome (SS). In most cases, medical providers advise against combined use of fluoxetine and trazodone for these reasons. However, in some cases, a medical provider may deem combination use beneficial. In such cases, patients should be aware of the potential complications, including SS, and should be closely monitored for signs of SS.

Ibuprofen (Advil)

Ibuprofen is a non-steroidal anti-inflammatory drug, or NSAID. NSAIDs have many uses, including reducing inflammation and fever. However, because they can prevent blood clotting, they can increase the risk of bleeding, especially upper GI bleeding; this risk may increase when taken together with fluoxetine.

Bupropion (Wellbutrin)

Wellbutrin (bupropion) is a popular antidepressant. Since it can affect levels of serotonin, there is increased risk of serotonin syndrome (SS) occurring when patients use both fluoxetine and bupropion simultaneously. SS is a potentially life-threatening condition that occurs when the central nervous system (CNS) is flooded with too much serotonin.

Vyvanse (Lisdexamfetamine)

Vyvanse (lisdexamfetamine) is a stimulant (specifically, an amphetamine derivative) that can help treat ADHD and other conditions. According to the FDA, concomitant (at-the-same-time) use of Vyvanse and fluoxetine can result in interactions, as experts have noted that fluoxetine can have “clinically important interactions with amphetamines.” Combining Vyvanse and fluoxetine can increase the risk of the potentially life-threatening condition known as serotonin syndrome (SS).

Food Interactions

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

Fluoxetine and Alcohol

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

Herbal Supplements        

Patients should not use fluoxetine with St. John’s wort (Hypericum perforatum), as negative interactions can occur, such as serotonin syndrome (SS).


While many websites claim that certain vitamins may enhance the effectiveness of antidepressants, patients should always clear any vitamins they are taking—both over the counter and prescription—before using them in combination with fluoxetine.

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
  • Patients with mania/hypomania in bipolar disorder
  • Patients with renal (kidney) impairment
  • Patients with seizure disorders

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.

Fluoxetine and Pregnancy

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

Fluoxetine and Breastfeeding

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

Hepatic Impairment

In patients with reduced liver function or otherwise affected metabolism, doses may require adjustments.

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 fluoxetine 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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