Drugs that interact with metoprolol
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Drug Interactions with Metoprolol
Introduction to Metoprolol and CYP2D6 Enzyme
Metoprolol is a widely used beta-receptor antagonist primarily metabolized by the cytochrome P450 (CYP) 2D6 enzyme. This enzyme plays a crucial role in the metabolism of various drugs, and its inhibition can lead to significant drug-drug interactions (DDIs) 12.
Antidepressants and Metoprolol Interactions
Potent CYP2D6 Inhibitors
Antidepressants such as paroxetine, fluoxetine, and bupropion are potent inhibitors of CYP2D6. These drugs can increase the biologically available dose of metoprolol by 4- to 6-fold, leading to severe adverse effects like bradycardia and atrioventricular block 12. Studies have shown that paroxetine significantly increases the area under the curve (AUC) of metoprolol, resulting in decreased systolic blood pressure and heart rate 25.
Moderate CYP2D6 Inhibitors
Other antidepressants, including escitalopram, citalopram, and duloxetine, are moderate inhibitors of CYP2D6. These drugs can cause a 2- to 3-fold increase in the biologically available dose of metoprolol, necessitating dose adjustments to avoid adverse effects 1.
Minimal CYP2D6 Inhibitors
Antidepressants such as sertraline, venlafaxine, mianserin, and mirtazapine have little to no effect on CYP2D6 and are not expected to cause clinically relevant interactions with metoprolol 1.
Antimalarial Drugs and Metoprolol
The antimalarial drug combination pyronaridine-artesunate (PA) has been shown to interact with metoprolol. Co-administration of PA with metoprolol results in a significant increase in the maximum concentration and AUC of metoprolol, likely due to pyronaridine-mediated CYP2D6 inhibition 3.
Over-the-Counter Medications and Metoprolol
Diphenhydramine
Diphenhydramine, a common over-the-counter antihistamine, is a potent inhibitor of CYP2D6. It significantly decreases the clearance of metoprolol, leading to prolonged negative effects on heart rate and blood pressure in individuals with high CYP2D6 activity 4.
Antiarrhythmic Drugs and Metoprolol
Propafenone
Propafenone, an antiarrhythmic drug, is also metabolized by CYP2D6 and acts as an inhibitor of this enzyme. Co-administration with metoprolol can lead to severe adverse effects, as evidenced by a pediatric case of mixed-drug intoxication resulting in cardiogenic shock and death 7.
Conclusion
Metoprolol interacts with various drugs primarily through the inhibition of the CYP2D6 enzyme. Potent inhibitors like paroxetine, fluoxetine, and bupropion significantly increase metoprolol levels, leading to severe adverse effects. Moderate inhibitors such as escitalopram and citalopram require dose adjustments, while minimal inhibitors like sertraline pose little risk. Additionally, over-the-counter medications like diphenhydramine and antiarrhythmic drugs like propafenone can also cause significant interactions. Careful consideration and monitoring are essential when co-prescribing these medications with metoprolol.
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