Drug interactions with metoprolol
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CYP2D6 Inhibition and Metoprolol Drug Interactions
Metoprolol is mainly broken down in the body by the enzyme CYP2D6. Many drug interactions with metoprolol happen because other drugs can block this enzyme, leading to higher levels of metoprolol in the blood and a greater risk of side effects like slow heart rate and low blood pressure 1238910.
Antidepressants and Metoprolol Interactions
Some antidepressants, especially paroxetine, fluoxetine, and bupropion, are strong inhibitors of CYP2D6. When taken with metoprolol, these drugs can increase metoprolol levels by 4- to 6-fold, raising the risk of serious side effects such as severe bradycardia and heart block 12. Other antidepressants like citalopram, escitalopram, and duloxetine are weaker inhibitors and can double or triple metoprolol levels, so dose reductions may be needed. Antidepressants such as sertraline, venlafaxine, mianserin, and mirtazapine have little to no effect on CYP2D6 and are safer to use with metoprolol .
Other CYP2D6 Inhibitors: Apatinib and Phellopterin
Apatinib, a cancer drug, also blocks CYP2D6 and can significantly increase metoprolol levels, especially in males, which may raise the risk of heart-related side effects . Phellopterin, found in some herbal medicines and citrus fruits, can irreversibly inhibit CYP2D6, leading to higher metoprolol concentrations in the blood .
Antiarrhythmic Drugs: Propafenone and Amiodarone
Propafenone, used for heart rhythm problems, can double to five-fold increase metoprolol levels by blocking its breakdown. This combination has led to adverse effects like nightmares and heart failure in some patients, and the metoprolol dose should be reduced if used together 78. Amiodarone, another antiarrhythmic, slightly inhibits CYP2D6 and can alter the levels of metoprolol’s active metabolite, but the clinical impact may be less pronounced compared to stronger inhibitors .
Benzodiazepines: Chlordiazepoxide
Chlordiazepoxide, a sedative, may reduce the heart rate-lowering effect of metoprolol after long-term use, possibly by increasing the activity of liver enzymes that break down metoprolol .
Clinical Implications and Recommendations
Most serious drug interactions with metoprolol involve drugs that strongly inhibit CYP2D6, leading to much higher metoprolol levels and increased risk of side effects 1238910. It is best to avoid combining metoprolol with strong CYP2D6 inhibitors like paroxetine, fluoxetine, bupropion, propafenone, and apatinib. If such combinations are necessary, close monitoring and dose adjustments are recommended 1238. Safer alternatives among antidepressants and beta-blockers should be considered when possible 126.
Conclusion
Metoprolol is prone to drug interactions, especially with medications that inhibit CYP2D6. These interactions can significantly increase metoprolol levels and the risk of adverse effects. Careful selection of co-prescribed drugs, dose adjustments, and monitoring are essential to ensure safe and effective use of metoprolol.
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