Bupropion × Metoprolol

Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 (bupropion SmPC), the main enzyme that clears metoprolol (metoprolol labels). The Spanish metoprolol SmPC lists bupropion among potent CYP2D6 inhibitors that raise metoprolol plasma levels. The FDA metoprolol label reports that strong CYP2D6 inhibitors doubled metoprolol concentrations; the documents give no figure for bupropion itself. Higher levels reduce the cardioselectivity of metoprolol (FDA metoprolol label). Bupropion keeps inhibiting the enzyme for at least 7 days after the last dose (bupropion SmPC).

Stronger metoprolol effect: slow pulse, dizziness, weakness, low blood pressure, including on standing, and fainting. Marked metoprolol excess can cause severe bradycardia, atrioventricular block, heart failure and bronchospasm (FDA metoprolol label). Because cardioselectivity is reduced, bronchospasm is a particular concern in asthma and chronic obstructive pulmonary disease.

If metoprolol is started in a patient on bupropion, begin at the lower end of the dose range. If bupropion is added to metoprolol, assess whether the metoprolol dose needs lowering and weigh the expected benefit of bupropion against the risk (Spanish bupropion SmPC). The FDA bupropion label also notes that the metoprolol dose may need to be decreased. The FDA metoprolol labels ask for close monitoring when a CYP2D6 inhibitor cannot be avoided, above all of heart rate and blood pressure. Bupropion keeps inhibiting the enzyme for at least 7 days after it is stopped, which matters when doses are changed (bupropion SmPC).