Atenolol with Diltiazem Interaction Details

Brand Names Associated with Atenolol

Brand Names Associated with Diltiazem

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 dilTIAZem with beta blockers slows AV conduction and can increase the risk of bradycardia[1]. DilTIAZem generally potentiates the pharmacologic effects of beta-adrenergic blocking agents, which may be useful in patients with normal heart function [2]. However, hypotension, left ventricular failure, and AV conduction disturbances have been reported when dilTIAZem has been added to beta blocker therapy. This is more likely to occur in the elderly and in patients with left ventricular dysfunction, aortic stenosis, or those patients using large doses of either drug [3]. DilTIAZem may also increase plasma concentrations of some hepatically metabolized beta blockers by 30% to 40% [4][5].

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. A dosage adjustment for hepatically metabolized beta blockers may be required. Concomitant use of dilTIAZem 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) The hemodynamic tolerability and safety of high-dose intravenous dilTIAZem was evaluated in patients with coronary artery disease receiving long-term metoprolol treatment [6]. DilTIAZem immediately decreased systemic vascular resistance, left ventricular systolic and mean aortic pressures (29%, 21% and 20%, respectively, at 5 minutes), and they remained significantly reduced at 30 minutes. There was little effect on heart rate or left ventricular contractility. PQ, QRS, and QTc intervals were not affected.

B) The effects of oral dilTIAZem and propranolol, alone and in combination with placebo were compared in 12 patients with stable-effort angina [7]. No clinically significant depression of left ventricular function was found in this study. However, significant bradyarrhythmias and/or systemic hypotension were noted in five of 12 patients. Each case responded to a reduction in dosage of both dilTIAZem and propranolol. The authors concluded that "high-dose" dilTIAZem alone appears to be as effective as, or more effective, than moderate-dose propranolol or the combination of dilTIAZem and propranolol in improving exercise tolerance, myocardial ischemia, and left ventricular function in patients with stable-effort angina.

C) DilTIAZem (30 mg orally three times daily) increased the area under the concentration-time curve (AUC) of propranolol and metoprolol by 30% to 40% and also increased the elimination half-life of these drugs in 13 healthy volunteers [5]. There was no effect on the plasma concentration of atenolol, a renally cleared beta blocking drug. dilTIAZem impaired the clearance of propranolol by inhibition of hepatic metabolism. Both d-propranolol and l-propranolol unbound clearance were decreased [4]. In addition, propranolol significantly decreased the resting pulse rate after dilTIAZem pretreatment as compared to placebo. The pharmacokinetic interaction between these two drugs may also be related to this effect. Other hepatically metabolized beta blockers may be similarly affected.

D) In a randomized, double-blind, Latin-square, placebo-controlled design involving four separate treatments, eight healthy male Japanese volunteers received a single drop of timolol 0.5% or artificial tears in each eye with or without a single oral dose of nicardipine 40 mg and with or without a single oral dose of dilTIAZem 60 mg. A single drop of timolol 0.5% reduced both heart rate and systolic blood pressure, showing evidence that ophthalmic timolol has systemic effects. Heart rate was increased after the administration of nicardipine, and this effect was reduced by ophthalmic timolol following exercise. Concurrent administration of the timolol eyedrops and both calcium antagonists also reduced systolic blood pressure both at rest and during exercise [8].

References

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

2 ) Glasser SP, Friedman R, Talibi T, et al: Safety and compatibility of betaxolol hydrochloride combined with diltiazem or nifedipine therapy in stable angina pectoris. Am J Cardiol 1994; 73:213-218.

3 ) Sagie A, Strasberg B, Kusnieck J, et al: Symptomatic bradycardia induced by the combination of oral diltiazem and beta blockers. Clin Cardiol 1991; 14:314-316.

4 ) Hunt BA, Bottorff MB, Herring VL, et al: Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers. Clin Pharmacol Ther 1990; 47:584-591.

5 ) Tateishi T, Nakashima H, Shitou T, et al: Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol. Eur J Clin Pharmacol 1989; 36:67-70.

6 ) Wiesfeld AC, Remme WJ, Look MP, et al: Acute hemodynamic and electrophysiologic effects and safety of high-dose intravenous diltiazem in patients receiving metoprolol. Am J Cardiol 1992; 70:997-1003.

7 ) Hung J, Hackett PL, Gordon SPF, et al: Pharmacokinetics of diltiazem in patients with unstable angina pectoris. Clin Pharmacol Ther 1988; 43:466-470.

8 ) Yatsuka YI, Tsutsumi K, & Kotegawa T: Interaction between timolol eyedrops and oral nicardipine or oral diltiazem in healthy Japanese subjects. Eur J Clin Pharmacol 1998; 54:149-154.

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.

Diltiazem Overview

• Diltiazem is used to treat high blood pressure and to control angina (chest pain). Diltiazem 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.

• High blood pressure is a common condition, and when not treated it 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.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.