Diltiazem and verapamil are two non-dihydropyridine calcium channel blockers (non-DHP CCBs) most commonly used in managing certain cardiac conditions. Even though they fall into the same medication class, these medications have important pharmacological differences that affect their role in clinical practice. In this post, I will provide a comparison of verapamil versus diltiazem and highlight important characteristics to consider when optimizing a patient’s medication regimen. 

Indication

Verapamil and diltiazem are commonly used non-DHP CCBs. This class of CCB works centrally within the heart, slowing contractility and lowering heart rate. Given their ability to affect the heart’s electrical system, they are commonly used for managing cardiac arrhythmias, like atrial fibrillation, as well as hypertension and angina.

Verapamil is also FDA-approved for cluster headaches and is typically considered a first-line prophylactic option for these patients. Therefore, if someone has a history of cluster headaches, verapamil would likely be the most appropriate non-DHP CCB. Great piece of info to know for your board exam!

Effectiveness

Comparative studies have found that both verapamil and diltiazem result in similar changes in ventricular rates when used for patients with atrial arrhythmias. Therefore, both medications hold similar efficacy for the management of atrial fibrillation. Although no direct head-to-head studies compare their effectiveness at lowering blood pressure, both medications have demonstrated efficacy as second-line therapy options for hypertension management.

Safety – Verapamil Versus Diltiazem

Key differences arise when comparing the safety profiles of verapamil versus diltiazem. Despite being in the same therapeutic class, verapamil and diltiazem have slightly different pharmacological effects. Both medications reduce heart rate, decrease cardiac output through negative inotropic effects, and increase vasodilation; however, verapamil is a much stronger negative inotrope. While negative inotropy can be beneficial for reducing strain on the heart, it may have a negative impact on those with comorbid conditions associated with weakened cardiac function. For example, the addition of verapamil to a patient with reduced cardiac output may be more likely to contribute to a heart failure exacerbation. This effect can sometimes be life-threatening, causing symptoms such as volume overload, pulmonary edema, peripheral edema, and ascites. While diltiazem is also a negative inotrope, its effect is much less pronounced. Therefore, if someone has weakened cardiac function, diltiazem may be the preferred therapy if one of these agents has to be used. However, it is important to note that neither agent is completely free of this effect and should both be avoided in those with pulmonary congestion, heart block, or impaired ventricular functioning if possible.

Another adverse effect more commonly associated with verapamil is constipation. Although typically not life-threatening, the presence of adverse effects like this one can influence patient compliance.

Convenience

While both medications are generic, in general, diltiazem is a modestly more expensive therapeutic option than verapamil, with some estimates of diltiazem being three times the cost of verapamil. This may lead to verapamil being the preferred therapeutic for individuals with high deductibles or without insurance coverage. However, one must also consider the potential costs associated with managing the adverse effects more commonly observed with verapamil, such as hospitalizations for heart failure exacerbations and constipation risk. These concerns could potentially outweigh the initial cost savings.

Diltiazem and verapamil are fairly similar in terms of other compliance measures. For example, they have similar formulations available, including intravenous solutions, immediate-release tablets/capsules, and extended-release tablets/capsules. 

In 2018, the FDA announced a national shortage of diltiazem. In this case, alternatives like verapamil were often considered for patients. While this shortage has obviously been resolved, it is important to consider the differences between these two medications if it were to occur again in the future.

Conclusion

In summary, while both verapamil and diltiazem have similar therapeutic effects, they differ significantly in their safety profiles and indications. Verapamil is the preferred agent in cluster headaches. While both agents should generally be avoided in those with decreased cardiac output,  the risk of heart failure exacerbation is greater with the use of verapamil given its strong negative inotropic effects. Overall, differences in cost, availability, safety, and indications require an individualized approach to prescribing non-DHP CCBs.

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This article was written by Christiana Carpenter, PharmD, Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

References

• Diltiazem. IBM Micromedex. IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.ezp3.lib.umn.edu/ (accessed  January 28, 2025).
• Verapamil. IBM Micromedex. IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.ezp3.lib.umn.edu/ (accessed  January 28, 2025).
• Drugs.com. Diltiazem vs Verapamil. Available at: https://www.drugs.com/compare/diltiazem-vs-verapamil. Accessed January 28, 2025.
• Aggarwal, A, Jain, A, Hughes, K. et al. Comparing Efficacy And Safety Of Verapamil Versus Diltiazem In Atrial Fibrillation And Flutter With Rapid Ventricular Response. JACC. 2020 Mar, 75 (11_Supplement_1) 527.
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• Forshay CM, Michael Boyd J, Rozycki A, Pilz J. The Safety and Efficacy of Verapamil Versus Diltiazem Continuous Infusion for Acute Rate Control of Atrial Fibrillation at an Academic Medical Center. Hosp Pharm. 2021;56(5):519-524. doi:10.1177/0018578720925388
• McKeever RG, Patel P, Hamilton RJ. Calcium Channel Blockers. [Updated 2024 Feb 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482473/
• Phillips BG, Gandhi AJ, Sanoski CA, Just VL, Bauman JL. Comparison of intravenous diltiazem and verapamil for the acute treatment of atrial fibrillation and atrial flutter. Pharmacotherapy. 1997;17(6):1238-1245.