Verapamil – Uses, Dosage and Side Effects

What is Verapamil?

Verapamil is a medication belonging to the class of calcium channel blockers (also called calcium antagonists). It is classified as a phenylalkylamine and has been used in clinical medicine since the 1960s. Verapamil works by blocking voltage-gated L-type calcium channels in the heart muscle and in the smooth muscle cells of blood vessel walls. This results in a reduced heart rate, decreased cardiac contractility, and relaxation of the blood vessels.

Indications

Verapamil is prescribed for a variety of cardiovascular conditions:

• Heart rhythm disorders (arrhythmias): Particularly supraventricular tachycardias (SVT), atrial fibrillation, and atrial flutter, where it is used to control heart rate.
• High blood pressure (hypertension): As a long-term therapy to lower elevated blood pressure.
• Angina pectoris: To prevent chest pain in stable angina and vasospastic angina (Prinzmetal angina).
• Hypertrophic obstructive cardiomyopathy (HOCM): In selected patients to relieve symptoms.

Mechanism of Action

Verapamil inhibits the influx of calcium ions into the cells of the heart muscle and vascular smooth muscle. The key pharmacological effects are:

• Negative chronotropic effect: Slows the heart rate by inhibiting the sinoatrial (SA) node.
• Negative dromotropic effect: Slows conduction through the atrioventricular (AV) node, which can terminate certain arrhythmias.
• Negative inotropic effect: Reduces the force of heart muscle contraction.
• Vasodilation: Relaxes the smooth muscle in blood vessel walls, lowering blood pressure and improving blood flow.

Dosage and Administration

Verapamil is available in several formulations: immediate-release tablets, extended-release tablets and capsules, and an intravenous (IV) solution for use in acute clinical settings. The appropriate dose is determined by the treating physician based on the indication, patient age, and overall health status.

• For hypertension and angina: typically 120–480 mg per day, taken in divided doses or as an extended-release formulation.
• For acute arrhythmias (IV): administered under close clinical monitoring due to the rapid onset of action.

Side Effects

Like all medications, verapamil can cause side effects. The most common and clinically relevant include:

• Constipation: One of the most frequently reported side effects, as calcium channels in the intestinal smooth muscle are also blocked.
• Low blood pressure (hypotension): Especially when standing up (orthostatic hypotension).
• Slow heart rate (bradycardia): Due to the negative chronotropic effect.
• AV block: Impaired electrical conduction between the atria and ventricles.
• Dizziness, headache, and fatigue.
• Ankle and leg swelling (peripheral edema).
• Nausea and gastrointestinal discomfort.

Contraindications

Verapamil must not be used in certain situations:

• Severe heart failure or significantly impaired left ventricular function.
• Second- or third-degree AV block (without a pacemaker).
• Sick sinus syndrome without a pacemaker.
• Combination with intravenous beta-blockers, due to the high risk of AV block and cardiac failure.
• Cardiogenic shock.
• Severe hypotension.

Drug Interactions

Verapamil interacts with a number of other medications. The most clinically important interactions include:

• Beta-blockers: Concurrent use can cause excessive slowing of the heart rate or AV block.
• Digoxin: Verapamil increases digoxin blood levels, raising the risk of digoxin toxicity.
• Simvastatin: Verapamil inhibits the CYP3A4 enzyme, leading to elevated statin levels and increased risk of muscle damage (myopathy).
• Ciclosporin and carbamazepine: Plasma levels of these drugs may increase due to CYP3A4 inhibition.
• Grapefruit juice: Can raise verapamil blood concentrations and should be avoided during treatment.

Patient Information

Verapamil should not be stopped abruptly without medical advice, as this may cause a rebound of arrhythmias or a rise in blood pressure. The medication should be taken regularly and at consistent times each day. Any unusual symptoms or side effects should be reported to a doctor promptly. Pregnant or breastfeeding women should only use verapamil if explicitly recommended by their physician.

References

1. European Medicines Agency (EMA): Summary of Product Characteristics for Verapamil-containing medicinal products, current version.
2. Brunton LL, Hilal-Dandan R, Knollmann BC (eds.) - Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th edition. McGraw-Hill Education, 2018.
3. Zipes DP, Camm AJ et al. - ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias. Circulation. 2006;114(10):e385-e484.