how does fluoxetine interact with metoprolol?

Fluoxetine is a medication that requires a prescription and is offered in various forms such as capsules, delayed-release capsules, tablets, and solutions, all of which are ingested orally. (Delayed-release capsules are designed to be absorbed into the body at a slower rate.)

The oral capsule form of fluoxetine is marketed under the brand name Prozac, but it is also available in a generic version, which is typically more cost-effective compared to branded versions. However, generic versions may not always be accessible in every strength or form as the branded ones.

Fluoxetine oral capsules may be utilized in combination therapy, necessitating concurrent use with other medications. Specifically, for managing depressive episodes associated with bipolar I disorder and treatment-resistant depression, this medication must be administered alongside olanzapine.

Metoprolol

Metoprolol is a medication that requires a prescription. It is available in immediate-release and extended-release oral tablet forms, as well as extended-release oral capsules. Additionally, there is an injectable form that is administered exclusively by healthcare professionals.

The oral tablets of Metoprolol are marketed under the brand names Lopressor and Toprol XL, and they are also available as generic versions, which are usually more cost-effective than the branded ones. However, it's important to note that generics may not always be offered in the same strengths or formulations as the brand-name drugs.

Both Lopressor and Toprol XL, along with their generic counterparts, contain metoprolol but in different salt forms. Lopressor contains metoprolol tartrate, while Toprol-XL contains metoprolol succinate. These variations in salt forms allow the medications to be used for different medical conditions.

Metoprolol succinate is an extended-release formulation, which means it stays in the bloodstream for a longer duration. On the other hand, metoprolol tartrate is an immediate-release formulation that acts more quickly.

How it works

Both metoprolol tartrate and metoprolol succinate belong to a category of medications known as beta-blockers. A drug class encompasses a group of medicines that function in a similar manner and are frequently used to address similar health conditions.

Elevated blood pressure often results from the constriction of blood vessels, placing added strain on the heart and increasing the body's demand for oxygen.

Beta-blockers operate by inhibiting norepinephrine (adrenaline) from binding to beta receptors located in blood vessels and the heart. This action prompts blood vessels to relax. Through this relaxation of blood vessels, beta-blockers assist in reducing heart rate and diminishing the heart's oxygen requirements. Consequently, this leads to a reduction in blood pressure and alleviation of chest pain.

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Pros and Cons of fluoxetine and metoprolol

Fluoxetine (Prozac):

Pros:

• Effective for Depression
• Long Half-Life
• FDA Approval
• Well-Tolerated
• Gradual Discontinuation

Cons:

• Side Effects
• Delayed Onset of Action
• Drug Interactions
• Suicidal Thoughts

Metoprolol:

Pros:

• Cardiovascular Benefits
• Reduced Heart Rate
• Stroke Prevention
• Well-Established
• Immediate and Extended Release Formulations

Cons:

• Side Effects
• Withdrawal Symptoms
• Masking Hypoglycemia Symptoms
• Not for Everyone

Differences Between fluoxetine and metoprolol

Fluoxetine: 

Used for treating depression, obsessive-compulsive disorder (OCD), panic disorder, bulimia nervosa, and premenstrual dysphoric disorder (PMDD).

Metoprolol: 

Used for treating hypertension, angina pectoris (chest pain), heart rhythm disorders such as atrial fibrillation, and for reducing the risk of heart attacks.

Alternative to fluoxetine and metoprolol

Fluoxetine Alternatives:

Sertraline: 

Another selective serotonin reuptake inhibitor (SSRI) used for depression, anxiety disorders, and related conditions.

Metoprolol Alternatives:

Atenolol: 

Another beta-blocker commonly used for hypertension and certain heart conditions.

Interactions between your drugs

metoprolol  fluoxetine

Limited clinical evidence indicates that selective serotonin reuptake inhibitors (SSRIs) may enhance the effects of certain beta-blockers. There have been instances where patients stabilized on beta-blocker therapy experienced bradycardia, hypotension, and complete heart block after starting an SSRI, leading to discontinuation of one or both medications and potentially requiring a permanent pacemaker. This interaction is supported by both in vitro and clinical studies involving paroxetine and metoprolol conducted by certain researchers.

The suggested mechanism behind this interaction involves SSRIs inhibiting CYP450 2D6, an enzyme responsible for metabolizing beta-blockers like carvedilol, labetalol, metoprolol, nebivolol, propranolol, and timolol. Paroxetine and norfluoxetine (an active metabolite of fluoxetine) are particularly potent inhibitors of CYP450 2D6 and may have a higher likelihood of causing this interaction. Conversely, fluvoxamine strongly inhibits CYP450 1A2 and may significantly interact with propranolol, which is metabolized by both CYP450 2D6 and 1A2.

In managing patients receiving both SSRIs and beta-blockers, it may be appropriate to start with a lower initial dose of the beta-blocker and titrate it cautiously. Close monitoring of cardiac function is essential, especially after starting, stopping, or changing the dosage of the SSRI in patients already stabilized on a beta-blocker regimen. Due to the prolonged elimination half-life of fluoxetine and norfluoxetine, the risk of interaction may persist for several weeks after discontinuing fluoxetine. To mitigate this risk, beta-blockers primarily eliminated by the kidneys (such as atenolol, acebutolol, betaxolol, carteolol, and nadolol) may be considered as alternatives.

Drug and food interactions

metoprolol  food

MODIFY DOSAGE SCHEDULE: Consuming food can increase the absorption of metoprolol.

HANDLING: Patients can be advised to take metoprolol consistently at a set time daily, ideally with or right after eating.

fluoxetine  food

Generally, it's best to steer clear of combining alcohol with CNS-active medications, as alcohol can amplify some of their effects. This combination can lead to increased depression of the central nervous system and may impair judgment, cognition, and motor skills.

To manage this potential interaction, patients taking CNS-active medications should be educated about the risks and advised to either avoid alcohol entirely or use it sparingly. Those who are mobile should be cautioned against engaging in activities that require full mental alertness and coordination until they understand how these medications impact them. If patients notice excessive or prolonged effects on their central nervous system that interfere with their daily activities, they should inform their healthcare provider.

metoprolol  food

ADJUST DOSAGE TIMING: When taken together with calcium salts, there could be a decrease in the oral absorption of atenolol and potentially other beta-blockers. The specific mechanism causing this interaction is not fully understood. In a study involving six healthy individuals, the administration of 500 mg of calcium (as lactate, carbonate, and gluconate) alongside atenolol (100 mg) resulted in a 51% reduction in the average peak plasma concentration (Cmax) and a 32% decrease in the area under the concentration-time curve (AUC) of atenolol. The elimination half-life of atenolol also increased by 44%. Furthermore, beta-blocking activity (measured by inhibiting exercise-induced tachycardia) was reduced twelve hours after taking the combination compared to atenolol alone. However, in a separate four-week study involving six hypertensive patients, there was no significant difference in blood pressure readings between treatments.

The researchers hypothesize that the prolonged elimination half-life caused by coadministering calcium may lead to the accumulation of atenolol over time, compensating for its reduced absorption.

To manage this interaction, it is advisable to separate the administration of beta-blockers and calcium products by at least two hours. Patients should also be monitored for any potential decrease in the beta-blocking effects after starting calcium therapy.

Conclusion

Fluoxetine can interact with metoprolol through its inhibition of the CYP450 2D6 enzyme, which is responsible for metabolizing metoprolol. This interaction can lead to increased levels of metoprolol in the body, potentially causing adverse effects such as bradycardia, hypotension, and complete heart block. Healthcare providers should be vigilant about this interaction and consider adjusting dosages or opting for alternative medications to mitigate potential risks in patients receiving both fluoxetine and metoprolol. Patients should also be educated about the potential for interaction and advised to report any unusual symptoms to their healthcare provider for proper evaluation and management.