Carvid Drug Interactions

Inhibitors of CYP2D6; Poor Metabolizers of Debrisoquin: Interactions of carvedilol with strong inhibitors of CYP2D6 (such as quinidine, fluoxetine, paroxetine, and propafenone) have not been studied, but these drugs would be expected to increase blood levels of the R(+) enantiomer of carvedilol. In clinical studies, poor 2D6 metabolizers had a higher rate of dizziness during up-titration resulting from the vasodilating effects of the higher concentrations of the alpha blocking R(+) enantiomer.
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.
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 is 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.
Ciclosporin: Due to wide interindividual variability in the dose adjustment required, it is recommended that ciclosporin concentrations be monitored closely after initiation of carvedilol and that the dose of ciclosporin be adjusted as appropriate.
Digoxin: Both carvedilol and digoxin slow atrioventricular conduction and decrease heart rate. Concomitant use may increase the risk of bradycardia. Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Thus, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol.
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 C_max. Exercise caution in patients taking inducers of mixed function oxidases (e.g., rifampicin) as serum carvedilol levels may be decreased, or inhibitors of mixed function oxidases (e.g., cimetidine) as serum carvedilol levels may be increased.
Calcium Channel Blockers: Coadministration with diltiazem has been associated with conduction disturbance (rarely with hemodynamic compromise). If carvedilol is to be administered with calcium channel blockers of the verapamil or diltiazem type, it is recommended that ECG and blood pressure be monitored.
Insulin or Oral Hypoglycemics: Agents with beta-blocking properties may enhance the blood-sugar-reducing effect of insulin and oral hypoglycemics. Therefore, in patients receiving insulin or oral hypoglycemic agents, regular monitoring of blood sugar is recommended.
Amiodarone: Amiodarone, and its metabolite desethyl amiodarone, inhibitors of CYP2C9 and P-glycoprotein, increased concentrations of the S(-) enantiomer of carvedilol by at least 2-fold. Coadministration of carvedilol with amiodarone or other CYP2C9 inhibitors (e.g., fluconazole) may increase the beta-blocking properties of carvedilol resulting in further slowing of heart rate or cardiac conduction. Observe patients for signs of bradycardia or heart block, particularly when one agent is added to pre-existing treatment with the other.
Anesthesia: During general anesthesia, be aware of the synergistic negative inotropic and hypotensive effects of carvedilol and anesthetic drugs.
Others: Carvedilol, as with other agents with beta-blocking activity, may potentiate the effect of other coadministered medicines that are antihypertensive in action (e.g., alpha₁-receptor antagonists) or have hypotension as part of their adverse effect profile.