Metoprolol interactions
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Metoprolol Interactions: A Comprehensive Overview
Metoprolol and CYP2D6 Inhibitors
Interaction with Diphenhydramine
Metoprolol, a beta-blocker metabolized primarily by the CYP2D6 enzyme, exhibits significant interactions with various drugs that inhibit this enzyme. One notable interaction is with the over-the-counter antihistamine diphenhydramine. Diphenhydramine acts as a potent competitive inhibitor of metoprolol metabolism, particularly in individuals with high CYP2D6 activity (extensive metabolizers). This inhibition results in a twofold decrease in metoprolol clearance and a prolonged effect on heart rate and blood pressure in these individuals .
Interaction with Antidepressants
Antidepressants, particularly those that inhibit CYP2D6, also significantly affect metoprolol metabolism. Paroxetine and fluoxetine, both potent CYP2D6 inhibitors, can increase metoprolol's bioavailability by four to six times, leading to severe bradycardia and atrioventricular block in some cases 24. Other antidepressants like citalopram, escitalopram, and duloxetine cause a two- to threefold increase in metoprolol levels, necessitating dose adjustments to avoid adverse effects . Conversely, antidepressants such as sertraline and venlafaxine, which have minimal CYP2D6 inhibition, do not significantly interact with metoprolol .
Interaction with Pyronaridine-Artesunate
The antimalarial combination pyronaridine-artesunate (PA) also interacts with metoprolol. Co-administration of PA with metoprolol results in a significant increase in metoprolol's maximum concentration and area under the curve (AUC), likely due to CYP2D6 inhibition by pyronaridine. This interaction underscores the need for careful monitoring when these drugs are used together .
Metoprolol and Genetic Variations
CYP2D6 Polymorphisms
Genetic variations in the CYP2D6 enzyme significantly impact metoprolol metabolism. Poor metabolizers, who constitute about 5.7% of the US population, exhibit approximately fivefold higher metoprolol exposure compared to normal metabolizers. This variation necessitates dose adjustments to avoid excessive drug accumulation and potential side effects .
Metoprolol and Other Drug Interactions
Interaction with Metformin
Metoprolol can also affect the pharmacokinetics of metformin. Co-administration with metoprolol decreases metformin's plasma concentration by enhancing its uptake in the liver, kidneys, and muscles. This interaction can lead to elevated lactic acid and uric acid levels, particularly with long-term use, highlighting the need for monitoring when these drugs are prescribed together .
Clinical Implications and Recommendations
Monitoring and Dose Adjustments
Given the significant interactions between metoprolol and various CYP2D6 inhibitors, it is crucial to monitor patients closely and adjust doses as necessary. For instance, when co-prescribing metoprolol with potent CYP2D6 inhibitors like paroxetine or fluoxetine, a substantial dose reduction of metoprolol is recommended to prevent adverse effects . Similarly, alternative medications with less potential for interaction should be considered when possible .
Genetic Testing
Considering the impact of CYP2D6 polymorphisms on metoprolol metabolism, genetic testing can be a valuable tool in personalizing treatment. Identifying poor metabolizers can help tailor metoprolol dosing to achieve optimal therapeutic outcomes while minimizing the risk of side effects .
Conclusion
Metoprolol's interactions with various drugs, particularly those affecting the CYP2D6 enzyme, underscore the importance of careful management and monitoring in clinical practice. Understanding these interactions and the role of genetic variations can help optimize treatment and enhance patient safety.
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