Verapamil and Penbutolol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Verapamil
Penbutolol
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of hypotension, bradycardia and slow AV conduction
Interaction Deep Dive
Concomitant use of verapamil with beta blockers slows AV conduction and can increase the risk of bradycardia1. 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 10. Cardiac risk is increased by left ventricular dysfunction, aortic stenosis, or large doses of either drug 111213. The reaction has occasionally been reported with ophthalmic beta blockers 14.
Why it happens (mechanism)
Additive cardiovascular effects, decreased metabolism of some beta blockers
Literature reports
6 reports — tap to read
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 2.
b) Pharmacodynamic interactions with propranolol, atenolol, metoprolol, and pindolol have been reported, with the most marked effects occurring with propranolol 34. 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 4. An interaction with metoprolol has also been reported 5. No significant pharmacokinetic interaction was seen between verapamil and propranolol 6.
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 7.
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 8.
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 9.
Common questions
Can I take Verapamil and Penbutolol together?
An increased risk of hypotension, bradycardia and slow AV conduction Always confirm with your pharmacist or prescriber before making any change.
How serious is the Verapamil and Penbutolol interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Verapamil or Penbutolol need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (14)
- Product Information: Lopressor(R) oral tablets, metoprolol tartrate oral tablets. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2023. DailyMed
- 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. PubMed
- 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.
- 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. PubMed
- 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.
- 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. DOI
- 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.
- 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.
- Product Information: Betagon(R), mepindolol. Schering S.p.A. Milan, Italy, 2000.
- Product Information: Covera HS(R), verapamil. Pharmacia Corporation, Chicago, IL, 2003. DailyMed
- 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. PubMed
- Zatuchni J: Bradycardia and hypotension after propranolol HCl and verapamil. Heart Lung 1985; 14:94-95.
- Winniford MD, Fulton KL, & Hillis LD: Symptomatic sinus bradycardia during concomitant propranolol-verapamil administration. Am Heart J 1985; 110:498. PubMed
- 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. DOI
Keep reading about Verapamil
Keep reading about Penbutolol
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