Verapamil with Atenolol Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Atenolol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

An increased risk of hypotension, bradycardia and slow AV conduction

Interaction Summary

Concomitant use of verapamil with beta blockers slows AV conduction and can increase the risk of bradycardia[1]. Verapamil and beta blockers both have direct negative inotropic effects, slow AV conduction, and will possibly potentiate hypotension, bradycardia, congestive heart failure, and conduction abnormalities [2]. Cardiac risk is increased by left ventricular dysfunction, aortic stenosis, or large doses of either drug [3][4][5]. The reaction has occasionally been reported with ophthalmic beta blockers [6].

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

If concurrent therapy is required, monitor cardiac function and blood pressure carefully, particularly in patients predisposed to heart failure. Concomitant use of verapamil with beta blockers slows AV conduction and can increase the risk of bradycardia[1].

Mechanism Of Interaction

Additive cardiovascular effects, decreased metabolism of some beta blockers

Literature Reports

A) Adverse effects that may occur with combined verapamil and beta blocker therapy are often associated with conduction problems (9% of patients), dyspnea or heart failure (8% of patients), hypotension or dizziness (5% of patients), and lethargy (2% of patients). The cardiovascular adverse effects led to treatment withdrawal in 5% to 8% of patients who received the combination. Intravenous verapamil combined with beta blocker therapy is contraindicated, and oral verapamil combined with beta blocker therapy should only be used in patients who do not have impaired left ventricular function [7].

B) Pharmacodynamic interactions with propranolol, atenolol, metoprolol, and pindolol have been reported, with the most marked effects occurring with propranolol [8][9]. It is likely that such interactions may occur with all beta blocking drugs, particularly in at-risk patients.

C) Concomitant therapy with oral atenolol and oral verapamil resulted in increased steady-state atenolol plasma levels in some patients during chronic oral maintenance therapy. More than a 100% increase in the atenolol area under the concentration-time curve (AUC) was observed in some of the ten patients in the study. However, the group comparisons did not achieve statistical significance [9]. An interaction with metoprolol has also been reported [10]. No significant pharmacokinetic interaction was seen between verapamil and propranolol [11].

D) Nine healthy volunteers received single oral doses of R-verapamil 120 mg or placebo with talinolol 50 mg during a randomized, crossover study. Coadministration of R-verapamil decreased the maximum concentration (Cmax) of talinolol from 149 ng/mL to 95 ng/mL and also decreased the area under the concentration-time curve (AUC) from 0 to 24 hours from 945 ng/h/mL to 721 ng/h/mL. The renal clearance of talinolol remained unaffected. Verapamil is extensively metabolized and is a substrate of both P-glycoprotein and cytochrome P450 3A isoenzymes. Talinolol is also a P-glycoprotein substrate. The ability of verapamil to decrease the oral bioavailability of talinolol is most likely dose dependent [12].

E) A 72-year-old female developed intractable cardiogenic shock during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. The patient had coronary atherosclerosis, liver cirrhosis, and bradycardia-tachycardia syndrome. A pacemaker was implanted and verapamil therapy was subsequently initiated. Cardiogenic shock was triggered with the addition of atenolol to her treatment regimen two weeks after implantation. An unsuccessful attempt was made to increase aortic pressure by high dose catecholamines and counterpulsation. Immediate elevation of aortic pressure occurred after intravenous administration of calcium chloride. The patient recovered and was discharged two weeks later [13].

F) Both verapamil and beta-blockers have direct negative inotropic effects, slow AV conduction, and can potentiate hypotension, bradycardia, congestive heart failure, and conduction abnormalities [14].

References

1 ) Product Information: Lopressor(R) oral tablets, metoprolol tartrate oral tablets. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2023.

2 ) Product Information: Covera HS(R), verapamil. Pharmacia Corporation, Chicago, IL, 2003.

3 ) McCourty JC, Silas JH, Tucker GT, et al: The effect of combined therapy on the pharmacokinetics and pharmacodynamics of verapamil and propranolol in patients with angina pectoris. Br J Clin Pharmacol 1988; 25:349-357.

4 ) Zatuchni J: Bradycardia and hypotension after propranolol HCl and verapamil. Heart Lung 1985; 14:94-95.

5 ) Winniford MD, Fulton KL, & Hillis LD: Symptomatic sinus bradycardia during concomitant propranolol-verapamil administration. Am Heart J 1985; 110:498.

6 ) Pringle SD & MacEwen CJ: Severe bradycardia due to interaction of timolol eye drops and verapamil. Br Med J Clin Res Ed 1987; 294:155-156.

7 ) Brouwer RM, Follath F, & Buhler FR: Review of the cardiovascular adversity of the calcium antagonist beta-blocker combination: implications for antihypertensive therapy. J Cardiovasc Pharmacol 1985; 7(suppl 4):S38-S44.

8 ) Bailey DG & Carruthers SG: Interaction between oral verapamil and beta-blockers during submaximal exercise: relevance of ancillary properties. Clin Pharmacol Ther 1991; 49:370-376.

9 ) Keech AC, Harper RW, Harrison PM, et al: Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man. Eur J Clin Pharmacol 1988; 35:363-366.

10 ) Keech AC, Harper RW, Harrison PM, et al: Pharmacokinetic interactions between oral metoprolol and verapamil for angina pectoris. Am J Cardiol 1986; 58:551-552.

11 ) 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 1991; 31:323-332.

12 ) Schwarz UI, Gramatte T, Krappweis J, et al: Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans. Clin Pharmacol Ther 1999; 65:283-290.

13 ) Sakurai H, Kei M, & Matsubara K: Cardiogenic shock triggered by verapamil and atenolol - a case report of therapeutic experience with intravenous calcium. Jpn Circ J 2000; 64:893-896.

14 ) Product Information: Betagon(R), mepindolol. Schering S.p.A., Milan, Italy, 2000.

Verapamil Overview

• Verapamil is used to treat high blood pressure and to control angina (chest pain). The immediate-release tablets are also used alone or with other medications to prevent and treat irregular heartbeats. Verapamil is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart and slows electrical activity in the heart to control the heart rate.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Atenolol Overview

• Atenolol is used alone or in combination with other medications to treat high blood pressure. It also is used to prevent angina (chest pain) and improve survival after a heart attack. Atenolol is in a class of medications called beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.