7 DRUG INTERACTIONS
7.1 Catecholamine Depleting Drugs and Monoamine Oxidate (MAO) Inhibitors
Catecholamine depleting drugs (e.g., reserpine) and monoamine oxidase (MAO) inhibitors) may have an additive effect when given with beta-blocking agents. Observe patients treated with metoprolol plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction.
7.3 CYP2D6 Inhibitors
Drugs that are strong inhibitors of CYP2D6, such as quinidine, fluoxetine, paroxetine, and propafenone, were shown to double metoprolol concentrations. While there is no information about moderate or weak inhibitors, these too are likely to increase metoprolol concentration. Increases in plasma concentration decrease the cardioselectivity of metoprolol [see Clinical Pharmacology (12.3)]. Monitor patients closely, when the combination cannot be avoided.
7.4 Digitalis, Clonidine, and Calcium Channel Blockers and Other Drugs that Decrease Heart Rate
Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease heart rate. Concomitant administration of beta-blockers with these and other drugs known to decrease heart rate such as sphingosine-1-phosphate receptor modulators (e.g. fingolimod) may result in additive heart rate lowering effects.
If clonidine and metoprolol are coadministered, withdraw the metoprolol several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, delay the introduction of beta-blockers for several days after clonidine administration has stopped.