Carvedilol should be administered cautiously with digoxin, calcium channel blockers (especially verapamil and dilti-azem) and other beta-blockers because an increase in the incidence of bradycardia and atrioventricular nodal conduction disturbances (second and third degree heart block) is expected. Because carvedilol can also increase serum digoxin concentrations by 16% , monitoring serum digoxin levels is recommended during concurrent therapy. Administration of carvedilol with other antihypertensives may result in excessive hypotension. Concurrent administration with other beta-blockers, calcium channel blockers or antiarrhythmic agents may also result in additive negative inotropic effects.
Carvedilol has not been reported to affect the international normalized ratio directly or to interact with the anticoagulant effects of warfarin.
Enzyme inhibitors (eg, cimetidine) and enzyme inducers (eg, rifampin, barbiturates) increase and decrease carvedilol concentrations, respectively. A 16% increase in carvedilol concentrations has been observed with co-administration of grapefruit juice (grapefruit juice contains substances that inhibit the oxidative enzymes CYP3A4 and CYP1A2). Because carvedilol is metabolized through CYP2D4 and CYP2C9 it should be administered cautiously with inhibitors of these enzymes, such as tricyclic antidepressants, selective serotonin reuptake inhibitors (especially fluoxetine, paroxetine), neuroleptics (especially fluphenazine, haloperidol, methotrimepra-zine, thioridazine) and antiarrhythmics (amiodarone, flecain-ide, propafenone, quinidine).