Verapamil

Verapamil is a well-characterised member of the calcium channel blocker (CCB) family, specifically classified under the phenylalkylamine subclass. It exerts its pharmacological effects primarily on the myocardium and vascular smooth muscle, making it an essential therapeutic agent in cardiovascular medicine. Verapamil’s mechanism of action involves the inhibition of L-type calcium channels, thereby reducing intracellular calcium concentrations. This leads to a reduction in myocardial contractility and vasodilation, culminating in decreased peripheral vascular resistance, lower oxygen demand, and overall improved cardiac efficiency. Its diverse applications in clinical practice underscore its significance in managing various cardiovascular conditions.

Image source Google

Uses

Verapamil is used extensively for managing a spectrum of cardiovascular disorders. Its primary indications include essential hypertension, where it aids in maintaining controlled blood pressure levels, and angina pectoris—both stable and vasospastic forms—by improving myocardial oxygenation. It also plays a vital role in treating supraventricular tachyarrhythmias, such as atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia (PSVT). Off-label, Verapamil is employed in preventing migraines and cluster headaches and occasionally for conditions such as hypertrophic cardiomyopathy. Its effectiveness and versatility are grounded in a robust evidence base supporting its use in both acute and chronic clinical scenarios.

Dosage and Administration

Verapamil dosing should be individualised, taking into account the patient’s clinical status, comorbidities, and therapeutic response. For hypertension, the standard oral dosage is typically 80–120 mg taken three times daily. In maintenance therapy, extended-release preparations (120–240 mg once or twice daily) are often favoured to enhance adherence. In acute arrhythmic emergencies, intravenous administration is appropriate, beginning with 5–10 mg over two minutes. If required, a second dose may be administered after 30 minutes. Continuous infusion protocols should be accompanied by meticulous haemodynamic and ECG monitoring.

Dose Adjustment in Different Diseases

Verapamil requires dose modifications in specific patient populations. In individuals with renal impairment, although Verapamil undergoes hepatic metabolism, impaired renal function can reduce clearance of active metabolites, necessitating dose adjustments and careful monitoring. In hepatic dysfunction, Verapamil metabolism is significantly slowed due to impaired cytochrome P450 activity. Initiation at lower doses with slow titration is strongly recommended. During pregnancy, Verapamil is classified as Category C. Preclinical studies show adverse fetal effects, but definitive human studies are lacking. Use during pregnancy is considered only if benefits justify potential risks, with appropriate fetal monitoring in place.

Effects and Side Effects

The pharmacological effects of Verapamil include a reduction in systemic vascular resistance, bradycardia, and improved control of cardiac rhythm disturbances. Common adverse reactions include constipation (due to smooth muscle relaxation), dizziness, nausea, headache, and fatigue. Some individuals experience peripheral oedema or facial flushing. More severe complications include hypotension, sinus bradycardia, varying degrees of AV block, and exacerbation of pre-existing heart failure. Prolonged therapy warrants periodic assessments of hepatic enzymes, renal function, and electrolytes (particularly potassium and magnesium levels).

How Verapamil Works

Verapamil functions by blocking L-type calcium channels located in the myocardium and vascular smooth muscle cells. This blockade results in decreased intracellular calcium, which reduces myocardial contractile force (negative inotropy), slows atrioventricular conduction (negative dromotropy), and decreases heart rate (negative chronotropy). It is particularly effective in arrhythmias that involve the AV node, such as AV nodal re-entrant tachycardia. Additionally, its vasodilatory effects decrease systemic vascular resistance, reduce cardiac workload, and enhance myocardial perfusion, making it especially beneficial in patients with ischaemic heart conditions.

Drug Combinations in Use and Considerations During Infusion

Verapamil is frequently combined with other cardiovascular medications such as beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics. These combinations can be beneficial but also pose a risk of excessive bradycardia, hypotension, or cardiac decompensation. Caution is advised when co-administering with beta-blockers due to the heightened risk of AV block. During intravenous infusion of Verapamil, continuous monitoring of ECG and blood pressure is essential. Infusion should be performed slowly and under controlled conditions. Emergency resuscitation equipment, including calcium gluconate, should be readily available to manage potential complications of calcium channel blockade.

Presentation or Form

Verapamil is available in multiple formulations to cater to both acute and chronic management strategies:

Form	Strength	Route
Tablet	40 mg, 80 mg	Oral
Extended-release tab	120 mg, 180 mg, 240 mg	Oral
Injection	2.5 mg/mL (2 mL ampoule)	Intravenous
Oral solution	20 mg/mL	Oral

Pharmacokinetics and Pharmacodynamics, and Bacterial Coverage

Verapamil has an oral bioavailability of 20–35% due to substantial first-pass metabolism in the liver. Peak plasma levels are achieved in 1–2 hours (immediate-release) and 5–7 hours (extended-release). It has a half-life of approximately 3–7 hours, prolonged with chronic administration. Verapamil is extensively metabolised by hepatic CYP3A4 enzymes, and less than 5% is excreted unchanged in urine. Pharmacodynamically, Verapamil exerts negative inotropic, chronotropic, and dromotropic effects. It does not possess antimicrobial activity and is not effective against any bacterial species.

Drug Interactions

Verapamil is a potent inhibitor of CYP3A4 and P-glycoprotein, leading to significant interactions with drugs such as digoxin, beta-blockers, and certain statins. It increases plasma digoxin levels, necessitating close monitoring. Co-administration with beta-blockers may result in AV block or severe hypotension. Statins like simvastatin accumulate in the presence of Verapamil, raising the risk of rhabdomyolysis. Rifampin and other enzyme inducers reduce Verapamil levels, undermining its efficacy. Verapamil also potentiates the effects of CNS depressants and other antihypertensives.

Comparison with Other Drugs in Same Category

Drug	Class	Major Use	Side Effect Profile	Dosing Frequency
Verapamil	Phenylalkylamine CCB	Hypertension, arrhythmias, angina	Constipation, bradycardia	2–3 times/day or ER
Diltiazem	Benzothiazepine CCB	Hypertension, angina, AF	Oedema, dizziness, rash	2–4 times/day
Amlodipine	Dihydropyridine CCB	Hypertension, angina	Peripheral oedema, flushing	Once/day

Precautions and Special Considerations

Prior to initiating Verapamil, a comprehensive baseline evaluation—including ECG, renal, and liver function tests—is essential. It should be used cautiously in patients with known AV conduction abnormalities or left ventricular dysfunction. Elderly patients exhibit heightened sensitivity and may require dose reductions. Grapefruit juice inhibits CYP3A4, increasing Verapamil plasma levels and risk of toxicity, and should be avoided. Patients must be advised to recognise and report signs of hypotension or bradycardia promptly.

Toxicity or Overdose and Antidote

Verapamil overdose presents with marked bradycardia, AV block, hypotension, and possible cardiac arrest. Management involves aggressive supportive care: IV fluids, calcium gluconate, atropine, and vasopressors such as dopamine or dobutamine. In some instances, temporary pacemaker insertion or intravenous lipid emulsions may be required. Activated charcoal is useful in early overdose to limit absorption. No specific antidote exists, so management is supportive and symptom-driven.

Recent Updates in 2025 and Guidelines

The 2025 ESC guidelines highlight the need for personalised Verapamil therapy, especially in polymorbid and elderly patients. Evidence supports the benefit of extended-release Verapamil in enhancing treatment adherence, reducing blood pressure variability, and minimising cardiovascular risk. Emerging investigations are exploring its neuroprotective effects and potential use in metabolic disorders such as type 2 diabetes, suggesting broader therapeutic applications.

Facts to Remember

Verapamil is a calcium channel blocker that reduces heart rate and blood pressure.
It should be avoided in patients with severe cardiac dysfunction.
Intravenous use requires continuous monitoring.
Extended-release forms improve compliance and safety.
Strong CYP3A4 inhibition affects drug metabolism.

Did You Know?

Verapamil was the first calcium channel blocker introduced into clinical practice. It continues to be a mainstay in arrhythmia treatment. Excitingly, current studies suggest Verapamil might enhance insulin sensitivity, opening potential new uses in endocrinology. Its ongoing utility in both neurological and cardiovascular spheres makes it a dynamic pharmacological agent.