Verapamil with Cimetidine Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Cimetidine

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

Interaction Effect

Increased verapamil concentrations and possible cardiovascular toxicity

Interaction Summary

Cimetidine in particular among H2 receptor antagonists can cause serum level elevations for most available calcium channel blockers, although clinically significant changes in hemodynamic response (heart rate, blood pressure) are most apparent only with nifedipine or diltiazem. The cimetidine-verapamil interaction is controversial, with some reports indicating enhanced oral verapamil bioavailability  and elimination half-life  with cimetidine, while others  indicate no kinetic interactions at all. Both alterations in hepatic metabolism of calcium channel blockers and increased bioavailability secondary to reduced gastric acidity secondary to H2 blocker use are possible mechanisms .

Severity

Minor

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Monitor the cardiovascular response (blood pressure, heart rate) of the calcium channel blocker if cimetidine is added to the regimen.

Mechanism Of Interaction

Decreased hepatic metabolism and increased bioavailability

Literature Reports

A) Intravenous (10 mg) and oral (120 mg) doses of verapamil were administered before and after seven days of treatment of cimetidine (300 mg every six hours). No alterations in total clearance of verapamil were observed following intravenous administration, however clearance decreased from 8713 mL/min to 5320 mL/min (0.145 to 0.089 L/hr) after oral administration of verapamil in combination with cimetidine. Due to wide variations in the data, this alteration was of borderline (p less than 0.07) significance. Cimetidine increased verapamil's bioavailability from 26.3% to 49.3% (p less than 0.006) which resulted from small, insignificant changes in the intravenous and oral area under the plasma concentration versus time curve. Despite the change in the pharmacokinetic parameters no changes in the duration of the PR interval prolongation was noted. Intravenous verapamil kinetics were unaltered. A 21% decrease in clearance of verapamil and 50% increase in elimination half-life (P less than 0.01) was observed after oral administration of cimetidine 1.2 grams daily for four days .

B) Another trial indicates that concomitant administration of intravenous verapamil and oral cimetidine 300 mg four times daily resulted in a reduction in intravenous verapamil clearance and prolongation of the half-life of verapamil by 50%. No correlation was observed between individual changes in verapamil clearance and hepatic blood flow. Cimetidine has been observed to reduce verapamil clearance by mechanisms other than changes in hepatic blood flow or volume of distribution, which was also unchanged in this report. Cimetidine may decrease verapamil clearance by the inhibition of hepatic microsomal enzymes (cytochrome P-450 system) .

C) Concomitant administration of oral or intravenous verapamil and cimetidine resulted in no pharmacokinetic or pharmacodynamic interaction as reported by . Verapamil hepatic extraction following oral dosing was not affected by cimetidine. The authors also suggest that  failed to demonstrate any significant changes in verapamil pharmacodynamics during concomitant cimetidine therapy, therefore, therapy with both drugs should produce no change in verapamil pharmacokinetics.

D) Cimetidine pretreatment did not significantly affect the elimination of single oral or intravenous doses of verapamil in eight healthy volunteers .

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.

Cimetidine Overview

• Cimetidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter cimetidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach. Cimetidine is in a class of medications called H₂ blockers. It decreases the amount of acid made in the stomach.

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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.