Metoprolol is a metabolic substrate for the cytochrome P450 isoenzyme CYP2D6. Drugs that act as enzyme-inducing and enzyme-inhibiting substances may exert an influence on the plasma level of metoprolol. Plasma levels of metoprolol may be raised by co-administration of compounds metabolised by CYP2D6, eg, antiarrhythmics, antihistamines, histamine-2-receptor antagonists, antidepressants, antipsychotics, and COX-2 inhibitors.The plasma concentration of metoprolol is lowered by rifampicin and may be raised by alcohol and hydralazine.
Patients receiving concomitant treatment with sympathetic ganglion-blocking agents, other β-blockers (ie, eye drops) or monoamine oxidase (MAO) inhibitors should be kept under close surveillance.
If concomitant treatment with clonidine is to be discontinued, the β-blocker medication should be withdrawn several days before clonidine.
A watch should be kept for possible negative inotropic and chronotropic effects when metoprolol is given together with calcium antagonists of the verapamil and diltiazem-type and/or antiarrhythmic agents. In patients treated with β-blockers, IV administration of calcium antagonists of the verapamil-type should not be given.
β-blockers may enhance the negative inotropic and negative dromotropic effect of antiarrhythmic agents (of the quinidine type and amiodarone).
Digitalis glycosides, in association with ß-blockers, may increase atrioventricular conduction time and may induce bradycardia. In patients receiving β-blocker therapy, inhalation anaesthetics enhance the cardiodepressant effect.
Concomitant treatment with indomethacin or other prostaglandin synthetase inhibiting drugs may decrease the antihypertensive effect of β-blockers.
Under certain conditions, when adrenaline is administered to patients treated with β-blockers, cardioselective β-blockers interfere much less with blood pressure control than nonselective β-blockers.
The dosages of oral antidiabetics may have to be readjusted in patients receiving β-blockers.