Metoprolol drug interactions
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Metoprolol Drug Interactions: A Comprehensive Overview
Introduction to Metoprolol and CYP2D6 Interactions
Metoprolol, a beta-blocker commonly used to treat cardiovascular conditions, is primarily metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. This makes it susceptible to drug-drug interactions (DDIs) with other substances that inhibit or induce CYP2D6. Understanding these interactions is crucial for optimizing therapeutic outcomes and minimizing adverse effects.
Metoprolol and Antidepressants: Significant Interactions
Paroxetine and Fluoxetine
Paroxetine and fluoxetine, both potent CYP2D6 inhibitors, significantly increase the plasma concentration of metoprolol. Studies have shown that paroxetine can increase the area under the curve (AUC) of metoprolol by three to five times, leading to pronounced decreases in systolic blood pressure and heart rate, and potentially causing bradycardia and atrioventricular block 146. Given these risks, alternative antidepressants or dose adjustments of metoprolol are recommended when co-prescribing these medications.
Other Antidepressants
Other antidepressants such as bupropion, escitalopram, citalopram, and duloxetine also inhibit CYP2D6 to varying extents, causing two- to six-fold increases in metoprolol levels. However, sertraline, venlafaxine, mianserin, and mirtazapine have minimal to no effect on CYP2D6 and are considered safer options for concurrent use with metoprolol .
Over-the-Counter Medications: Diphenhydramine
Diphenhydramine, a common over-the-counter antihistamine, is a potent competitive inhibitor of CYP2D6. In individuals with high CYP2D6 activity (extensive metabolizers), diphenhydramine significantly reduces the clearance of metoprolol, thereby prolonging its effects on heart rate and blood pressure. This interaction is less pronounced in poor metabolizers .
Antimalarial Drugs: Pyronaridine-Artesunate
The antimalarial combination pyronaridine-artesunate (PA) also interacts with metoprolol by inhibiting CYP2D6. Co-administration of PA with metoprolol results in a significant increase in metoprolol's maximum concentration and AUC, necessitating careful monitoring and potential dose adjustments .
Antiarrhythmic Agents: Propafenone
Propafenone, another CYP2D6 substrate, can increase metoprolol levels two- to five-fold when co-administered. This combination has been associated with adverse effects such as severe nightmares and left ventricular failure, indicating the need for dose reduction of metoprolol when used with propafenone .
Oral Contraceptives
Oral contraceptives (OCs) containing estrogen and ethinyl estradiol can inhibit hepatic microsomal enzymes, leading to higher plasma concentrations of metoprolol. This interaction, although statistically significant, is generally considered to have a small clinical impact .
Metoprolol and Metformin
Interestingly, metoprolol can decrease the plasma concentration of metformin by enhancing its uptake in the liver, kidneys, and muscles. This interaction may lead to elevated levels of lactic acid and uric acid, highlighting the need for monitoring when these drugs are co-administered .
Conclusion
Metoprolol's interactions with various drugs, particularly those affecting CYP2D6, can significantly alter its pharmacokinetics and pharmacodynamics. Clinicians should be aware of these interactions to adjust dosages appropriately and monitor for adverse effects, ensuring safe and effective use of metoprolol in combination therapies.
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