Verapamil with Erythromycin Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 03, 2023

Interaction Effect

Increased verapamil exposure and an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, bradycardia, hypotension, cardiac arrest)

Interaction Summary

Coadministration of erythromycin and a CYP3A substrate (such as verapamil) may elevate drug concentrations of the CYP3A substrate, which may increase or prolong both therapeutic and adverse effects. Serious adverse reactions have been reported with concomitant use of erythromycin and CYP3A4 substrates, including hypotension with calcium channel blockers. The rate of sudden, cardiac-related death was 5-fold higher in patients receiving concomitant treatment with erythromycin and cytochrome P450/3A inhibitors diltiazem or verapamil, compared with controls . Consider dosage adjustments, and when possible, closely monitor drug concentrations of CYP3A substrates in patients concurrently receiving erythromycin . If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of erythromycin and a CYP3A substrate (such as verapamil) may elevate drug concentrations of the CYP3A substrate, which may increase or prolong both therapeutic and adverse effects. Serious adverse reactions have been reported with concomitant use of erythromycin and CYP3A4 substrates, including hypotension with calcium channel blockers. Consider dosage adjustments, and when possible, closely monitor drug concentrations of CYP3A substrates in patients concurrently receiving erythromycin. If clinically appropriate, consider the use of azithromycin (which does not inhibit CYP3A4) if treatment with a macrolide is required .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism by erythromycin

Literature Reports

A) Coadministration of macrolide antibiotics erythromycin or clarithromycin with a calcium channel blocker was associated with significantly increased short-term risk of hospital admission within 7 days for hypotension or shock ([OR, 5.8; 95% CI, 2.25 to 14.98] or [OR, 3.7; 95% CI, 2.26 to 6.06]) in a case-crossover cohort study of geriatric patients (N=7100); there was no significant risk associated with azithromycin. Calcium channel blocker treatment included diltiazem (40%), amlodipine (29.6%), NIFEdipine (19.4%), verapamil (8%), or felodipine (3%). The findings suggest that erythromycin and clarithromycin potentiate calcium channel blockers (CYP3A4 substrates) by inhibiting CYP3A4; azithromycin does not inhibit CYP3A4 .

B) Pronounced cardiotoxicity developed in a 79-year-old woman after erythromycin was coadministered with her previously stable dose regimen of verapamil. For 5 years prior to admission, the woman had received sustained-release verapamil 240 milligrams (mg) twice daily without incident, and had tolerated the recent addition of ramipril 2.5 mg daily to her treatment regimen. One week after beginning erythromycin 2000 mg/day for treatment of an upper respiratory infection, the patient required hospital admission with symptoms of dizziness, hypotension (blood pressure of 80/40 millimeters mercury), bradycardia, complete (3rd degree) atrioventricular block with a ventricular escape rhythm of 50/minute, and QTc interval prolongation (583 milliseconds (msec)). Erythromycin and verapamil were immediately discontinued, accompanied by fluid resuscitation, vasopressor support and supplemental calcium. Blood pressure and heart rate increased shortly thereafter. Within 2 days, the patient's electrocardiogram showed restoration of normal sinus rhythm (P-R interval within normal limits) and on hospital day 4, the QTc interval had returned to within normal range (418 msec) .

C) The rate of sudden, cardiac-related death was 5-fold higher in patients receiving concomitant treatment with erythromycin and cytochrome P450/3A inhibitors diltiazem or verapamil, compared with a control group treated with neither P450/3A inhibitors nor study antibiotics (amoxicillin and erythromycin). In a prospective cohort study, eligible patients treated with erythromycin were followed for a period up to 6 years to compare the incidence of sudden death from cardiac causes (presumed to arise from ventricular tachyarrhythmia) against the presence or absence of concurrent treatment with diltiazem or verapamil. Whereas the risk of sudden, cardiac-related death was doubled over baseline for patients currently receiving treatment with erythromycin alone, the relative risk of cardiac-related fatality increased 5-fold over control values for patients receiving concurrent treatment with erythromycin and either diltiazem or verapamil (cumulative incidence rate ratio = 5.35 (95% confidence interval, 1.72 to 16.64; p=0.004).

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.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as erythromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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.