Summary

Paroxetine can significantly increase metoprolol blood levels by inhibiting the CYP2D6 enzyme responsible for metoprolol metabolism. This interaction may lead to enhanced beta-blocking effects, including excessive bradycardia, hypotension, and potential cardiovascular complications.

Introduction

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression, anxiety disorders, and panic disorder. It is known as a potent inhibitor of the CYP2D6 enzyme. Metoprolol is a selective beta-1 adrenergic receptor blocker used to treat hypertension, angina, heart failure, and for secondary prevention after myocardial infarction. Metoprolol is extensively metabolized by the CYP2D6 enzyme, making it susceptible to interactions with CYP2D6 inhibitors like paroxetine.

Mechanism of Interaction

The interaction occurs through paroxetine's potent inhibition of the cytochrome P450 2D6 (CYP2D6) enzyme. Metoprolol is primarily metabolized by CYP2D6 through alpha-hydroxylation and O-demethylation pathways. When paroxetine inhibits CYP2D6, it significantly reduces metoprolol's metabolism, leading to increased plasma concentrations and prolonged half-life of metoprolol. This results in enhanced and prolonged beta-blocking effects, as the active drug remains in the system longer than expected.

Risks and Symptoms

The primary clinical risks include excessive beta-blockade effects such as severe bradycardia (heart rate below 50 bpm), hypotension, fatigue, dizziness, and potential heart block. Patients may experience worsening of heart failure symptoms if predisposed. The interaction is particularly concerning in elderly patients or those with existing cardiovascular conditions. In severe cases, the combination may lead to cardiogenic shock or complete heart block requiring emergency intervention. The interaction typically develops within days to weeks of starting paroxetine in patients already on metoprolol.

Management and Precautions

Close cardiovascular monitoring is essential when initiating this combination. Monitor heart rate, blood pressure, and ECG regularly, especially during the first few weeks. Consider reducing metoprolol dose by 25-50% when starting paroxetine, with gradual titration based on clinical response. Alternative antidepressants with minimal CYP2D6 inhibition (such as sertraline, citalopram, or escitalopram) should be considered. If the combination is necessary, use the lowest effective doses and educate patients about signs of excessive beta-blockade. Regular follow-up appointments are crucial to assess tolerance and adjust dosing as needed.

Paroxetine interactions with food and lifestyle

Alcohol: Paroxetine may increase the sedative effects of alcohol. Patients should avoid or limit alcohol consumption while taking paroxetine, as the combination can enhance drowsiness, dizziness, and impair cognitive and motor functions. This interaction is consistently warned against in clinical guidelines due to the potential for increased central nervous system depression.

Metoprolol interactions with food and lifestyle

Alcohol: Metoprolol may enhance the blood pressure-lowering effects of alcohol, potentially causing excessive hypotension, dizziness, or fainting. Patients should limit alcohol consumption and monitor for symptoms of low blood pressure when drinking alcohol while taking metoprolol. Food: Taking metoprolol with food can increase its absorption and bioavailability. For immediate-release metoprolol tartrate, taking with food is recommended to improve absorption and reduce gastrointestinal side effects. Extended-release metoprolol succinate should be taken consistently either with or without food to maintain steady blood levels. Exercise: Metoprolol blocks the heart's response to exercise by reducing heart rate and blood pressure response to physical activity. Patients should be aware that their usual heart rate targets during exercise may not be achievable, and they should monitor for symptoms like excessive fatigue, shortness of breath, or dizziness during physical activity. Exercise capacity may be reduced, and patients should consult their healthcare provider about appropriate exercise levels.