There are several medications that are contraindicated, should be avoided, or require close monitoring if they are concomitantly used with carvedilol.1-5
CYP2D6 enzyme inhibitor medications and poor metabolizers. The CYP2D6 enzyme is involved in the metabolism of carvedilol. Patients who are poor CYP2D6 metabolizers and patients who are taking CYP2D6 inhibitors concomitantly with carvedilol have increased risk of experiencing carvedilol toxicity.6,7 Examples of CYP2D6 enzyme inhibitors include: Fluoxetine, paroxetine, propafenone, and quinidine.5
Rifampin. Concomitant use of rifampin and carvedilol may decrease carvedilol levels by up to 70%,5,8 by upregulating carvedilol intestinal secretion.9
Hypotensive agents. Concomitant use of carvedilol and hypotensive agents (e.g., reserpine, monoamine oxidase inhibitors, and clonidine) that can deplete catecholamine should be avoided as it may increase the risk of hypotension and severe bradycardia.1-4
Cyclosporine. Concomitant use of cyclosporine and carvedilol increases cyclosporine levels, and about a 20% reduction in cyclosporine dose is recommended.1-4,10-12
Digitalis glycosides. Concomitant use of digitalis glycosides and carvedilol increases digoxin levels13,14 by about1,3,4 15% and up to about 30%.2 Both digitalis glycosides and beta blockers slow atrioventricular conduction and decrease heart rate, and their concomitant use can increase the risk of bradycardia.1,3,4
Amiodarone. Concomitant use of amiodarone and carvedilol may increase carvedilol levels15,16 and result in slowing of heart rate or cardiac conduction.1,3,4
Calcium channel blockers. Concomitant use of calcium channel blockers, specifically verapamil or diltiazem, and carvedilol may result in slowing the heart rate, conduction disturbances, and affect ECG and blood pressure.1-4
Insulin and oral hypoglycemic. Concomitant use of insulin or oral hypoglycemic and carvedilol may enhance hypoglycemic action.1-4 Beta blockers can also mask hypoglycemia signs and symptoms when used with antidiabetic medications.5,17
- APO-Carvedilol [package insert]. Toronto, Canada: Apotex Pharmaceutical Holdings Inc.; 2015.
- Auro-Carvedilol [package insert]. Ontario, CA: Aurobindo Pharma Inc.; 2013.
- Coreg [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- Coreg CR [package insert]. Ciales, PR: GK Pharmaceuticals Contract Manufacturing Operations; 2008.
- Vanderhoff BT, Ruppel HM, Amsterdam PB. Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998;58(7):1627-1634, 1641-1622.
- Samer CF, Lorenzini KI, Rollason V, Daali Y, Desmeules JA. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013;17(3):165-184.
- Lymperopoulos A, McCrink KA, Brill A. Impact of CYP2D6 genetic variation on the response of the cardiovascular patient to carvedilol and metoprolol. Curr Drug Metab. 2015;17(1):30-36.
- Keating GM, Jarvis B. Carvedilol. Drugs. 2003;63(16):1697-1741.
- Giessmann T, Modess C, Hecker U, et al. CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects. Clin Pharmacol Ther. 2004;75(3):213-222.
- Amioka K, Kuzuya T, Kushihara H, Ejiri M, Nitta A, Nabeshima T. Carvedilol increases ciclosporin bioavailability by inhibiting P-glycoprotein-mediated transport. J Pharm Pharmacol. 2007;59(10):1383-1387.
- Bader FM, Hagan ME, Crompton JA, Gilbert EM. The effect of beta-blocker use on cyclosporine level in cardiac transplant recipients. J Heart Lung Transplant. 2005;24(12):2144-2147.
- Kaijser M, Johnsson C, Zezina L, Backman U, Dimeny E, Fellstrom B. Elevation of cyclosporin A blood levels during carvedilol treatment in renal transplant patients. Clin Transplant. 1997;11(6):577-581.
- De Mey C, Brendel E, Enterling D. Carvedilol increases the systemic bioavailability of oral digoxin. Br J Clin Pharmacol. 1990;29(4):486-490.
- Wermeling DP, Field CJ, Smith DA, Chandler MH, Clifton GD, Boyle DA. Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension. Pharmacotherapy. 1994;14(5):600-606.
- Horiuchi I, Kato Y, Nakamura A, Ishida K, Taguchi M, Hashimoto Y. Inhibitory and stimulative effects of amiodarone on metabolism of carvedilol in human liver microsomes. Bio Pharm Bull. 2010;33(4):717-720.
- Fukumoto K, Kobayashi T, Komamura K, Kamakura S, Kitakaze M, Ueno K. Stereoselective effect of amiodarone on the pharmacokinetics of racemic carvedilol. Drug Metab Pharmacokinet. 2005;20(6):423-427.
- Frishman WH. Carvedilol. N Engl J Med. 1998;339(24):1759-1765.