(Also see Precautions).
Pharmacokinetic interactions: Digoxin: Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Both digoxin and carvedilol slow AV conduction. Increased monitoring of digoxin levels is recommended when initiating, adjusting or discontinuing carvedilol.
Insulin or oral hypoglycemic: Agents with beta-blocking properties may enhance the blood-sugar-reducing effect of insulin and oral hypoglycemic. The signs of hypoglycemia may be masked or attenuated (especially tachycardia). In patients taking insulin or oral hypoglycemic, regular monitoring of blood glucose is therefore recommended.
Inducers and inhibitors of hepatic metabolism: Rifampicin reduced plasma concentrations of carvedilol by about 70%. Cimetidine increased AUC by about 30% but caused no change in Cmax. Care may be required in those patients receiving inducers of mixed function oxidases e.g. rifampicin, as serum levels of carvedilol may be reduced, or inhibitors of mixed function oxidases e.g. cimetidine, as serum levels of carvedilol may be increased.
However, based on the relatively small effect of cimetidine on carvedilol drug levels, the likelihood of any clinically important interaction is minimal.
Catecholamine-depleting agents: Patients taking both agents with beta-blocking properties and a drug that can deplete catecholamines (e.g. reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia.
Cyclosporine: Modest increased in mean trough cyclosporine concentrations were observed following initiation of carvedilol treatment in renal transplant patients suffering from chronic vascular rejection. In about 30% of patients, the dose of cyclosporine had to be reduced in order to maintain cyclosporine concentrations within the therapeutic range, while in the remainder no adjustment was needed. On average, the dose of cyclosporine was reduced about 20% in these patients. Due to wide inter-individual variability in the dose adjustment required. It is recommended that cyclosporine concentrations be monitored closely after initiation of carvedilol therapy and that the dose of cyclosporine be adjusted as appropriate.
Verapamil, diltiazem, or other antiarrhythmics: In combination with carvedilol can increase the risk of AV conduction disturbances (see Precautions).
Pharmacodynamic interactions: Clonidine: Concomitant administration of clonidine with agents with beta-blocking properties may potentiate blood-pressure and heart-rate-lowering effects. When concomitant treatment with agents with beta-blocking properties and clonidine to be terminated, the beta-blocking agent should be discontinued first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage.
Calcium channel blockers (see Precautions): Isolated cases of conduction disturbances (rarely with hemodynamic compromise) have been observed when carvedilol is co-administerd with diltiazem. As with other agents with beta-blocking properties. If carvedilol is to be administered orally with calcium channel blockers of the verapamil or diltiazem type, it is recommended that ECG and blood pressure be monitored.
As with other agents with beta-blocking activity, carvedilol may potentiate the effect of other concomitantly administered drugs that are anti-hypertensive in action (e.g. alpha1-receptor antagonist) or have hypotension as part of their adverse effect profile.
Careful attention must be paid during anesthesia to the synergistic negative inotropic and hypotensive effects of carvedilol and anesthesia drugs.
Certain sedatives (barbiturates, phenothiazines) and drugs for treating depression (tricyclic antidepressant), vasodilating drugs and alcohol may intesify the blood pressure lowering effect.