Basic Information
ID DDInter675 and DDInter561
Interaction Additive reductions in heart rate, cardiac conduction, and cardiac contractility may occur when calcium channel blockers, especially verapamil and diltiazem, are used concomitantly with beta blockers. While this combination may be useful and effective in some situations, potentially serious cardiovascular adverse effects such as congestive heart failure, severe hypotension, and/or exacerbation of angina may occur. Ventricular asystole, sinus arrest, and heart block have also been reported.
Management Close clinical monitoring of patient hemodynamic response and tolerance is recommended if these agents are used together, and the dosage of one or both agents adjusted as necessary. Patients should be advised to promptly report any symptoms including fatigue, headache, fainting, swelling of the extremities, weight gain, shortness of breath, chest pain, increased or decreased heartbeat, or irregular heartbeat.
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Eur J Clin Pharmacol 35 (1988): 363-6 [12] Wayne VS, Harper RW, Laufer E, et al "Adverse interaction between beta-adrenergic blocking drugs and verapamil: report of three cases." Aust N Z J Med 12 (1982): 285-9 [13] Eisenberg JN, Oakley GD "Probable adverse interaction between oral metoprolol and verapamil." Postgrad Med J 60 (1984): 705-6 [14] Murdoch DL, Thomson GD, Thompson GG, et al "Evaluation of potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol in normal subjects." Br J Clin Pharmacol 31 (1991): 323-32 [15] Sagie A, Strasberg B, Kusnieck J, Sclarovsky S "Symptomatic bradycardia induced by the combination of oral diltiazem and beta blockers." Clin Cardiol 14 (1991): 314-6 [16] Pringle SD, MacEwen CJ "Severe bradycardia due to interaction of timolol eye drops and verapamil." Br Med J 294 (1987): 155-6 [17] Keech AC, Harper RW, Harrison PM, Pitt A, McLean AJ "Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man." Eur J Clin Pharmacol 35 (1988): 363-6 [18] Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6 [19] Leon MB, Rosing DR, Bonow RO, Epstein SE "Combination therapy with calcium-channel blockers and beta blockers for chronic stable angina pectoris." Am J Cardiol 55 (1985): b69-80 [20] Minish T, Herd A "Symptomatic bradycardia secondary to interaction between topical timolol maleate, verapamil, and flecainide: a case report." J Emerg Med 22 (2002): 247-9 [21] Anastassiades CJ "Nifedipine and beta-blocker drugs." Br Med J 281 (1980): 1251-2 [22] Pieper JA, Miller JH "Serum protein binding interactions between propranolol and calcium channel blockers." Drug Intell Clin Pharm 18 (1984): 492 [23] Lee TH, Salomon DR, Rayment CM, Antman EM "Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil-propranolol therapy." Am J Med 80 (1986): 1203-4 [24] Hunt BA, Bottorff MB, Herring VL, Self Th, Lalonde RL "Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers." Clin Pharmacol Ther 47 (1990): 584-91 [25] McCourty JC, Silas JH, Tucker GT, Lennard MS "The effect of combined therapy on the pharmacokinetics and pharmacodynamics of verapamil and propranolol in patients with angina pectoris." Br J Clin Pharmacol 25 (1988): 349-57 [26] Schoors DF, Vercruysse I, Musch G, Massart DL, Dupont AG "Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers." Br J Clin Pharmacol 29 (1990): 497-501 [27] Ronn O, Bengtsson B, Edgar B, Raner S "Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol." Drugs 29 (1985): 16-25 [28] "Product Information. Toprol-XL (metoprolol)" Astra-Zeneca Pharmaceuticals, Wilmington, DE. [29] Lee TH, Salomon DR, Rayment CM, Antman EM "Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil/propranolol therapy." Am J Med 80 (1986): 1203-4 [30] Reddy PS, Uretsky BF, Steinfeld M "The hemodynamic effects of intravenous verapamil in patients on chronic propranolol therapy." Am Heart J 107 (1984): 97-101 [31] Zatuchni J "Bradycardia and hypotension after propranolol HCI and verapamil." Heart Lung 14 (1985): 94-5 [32] Sinclair NI, Benzie JL "Timolol eye drops and verapamil: a dangerous combination." Med J Aust 1 (1983): 548 [33] McCourty JC, Silas JH, Tucker GT, Lennard MS "The effect of combined therapy on the pharmacokinetics and pharmacodynamics of verapamil and propranolol in patients with angina pectoris." 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Alternative for Esmolol -
Alternative for Diltiazem C05A
Nitroglycerin Zinc chloride Triamcinolone Prednisolone Hydrocortisone Fluocinonide
Fluocinolone acetonide Zinc acetate Zinc gluconate Tetracaine Procaine
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.