Fluoxetine with Metoprolol Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Metoprolol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased metoprolol exposure

Interaction Summary

The concomitant use of metoprolol (a CYP2D6 substrate) with a strong CYP2D6 inhibitor may increase the exposure of metoprolol, thereby decreasing metoprolol cardioselectivity. If concomitant administration is required, monitor the patient closely.

Severity

Moderate

Onset

Unspecified

Evidence

Established

How To Manage Interaction

The concomitant use of metoprolol (a CYP2D6 substrate) with a strong CYP2D6 inhibitor may increase the exposure of metoprolol, thereby decreasing metoprolol cardioselectivity. If concomitant administration is required, monitor the patient closely.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism of metoprolol

Literature Reports

A) For both S- and R-metoprolol, the mean AUC was increased approximately 3-fold and 4-fold (respectively) and the Cmax was increased by 2- to 3-fold of both tartrate and succinate formulations by paroxetine (a strong CYP2D6 inhibitor) in an open-labeled cross-over study of healthy patients with at least 1 active CYP2D6 allele (N=15). Paroxetine coadministered with metoprolol also lowered exercise heart rate and systolic blood pressure when compared with metoprolol administration alone, representing an increase in the magnitude and duration of beta-blockade. Exercise heart rate was significantly lower at the 2-hour time point with paroxetine coadministered with metoprolol tartrate than with metoprolol succinate .

B) In healthy subjects with CYP2D6 extensive metabolizer phenotype, coadministration of quiNIDine 100 mg, a potent CYP2D6 inhibitor, and immediate-release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. In four patients with cardiovascular disease, coadministration of propafenone 150 mg thrice daily with immediate-release metoprolol 50 mg thrice daily increased the steady-state metoprolol concentration 2- to 5-fold compared to metoprolol alone. Extensive metabolizers who concomitantly use CYP2D6 inhibiting drugs will have increased (several-fold) metoprolol blood levels, decreasing metoprolol's cardioselectivity .

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Metoprolol Overview

• Metoprolol is used alone or in combination with other medications to treat high blood pressure. It also is used to treat chronic (long-term) angina (chest pain). Metoprolol is also used to improve survival after a heart attack. Metoprolol also is used in combination with other medications to treat heart failure. Metoprolol is in a class of medications called beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.