Class IV antiarrhythmic drugs block open or inactivated voltage-sensitive L-type Ca²⁺ channels.

Their actions are use-dependent and prevent repolarization until dissociating from the channel, decreasing the phase 4 depolarization rate.

This slows the SA and AV nodes' conduction, lengthens the effective refractory period, and decreases the heart rate. Together, these actions suppress ectopic beats.

Class IV drugs include nondihydropyridines, like verapamil and diltiazem.

Verapamil, the prototype drug of this class, is a racemic mixture with the ʟ-enantiomer having a greater inhibitory effect on calcium ion influx. It causes PR  interval prolongation.

Intravenously administered, verapamil causes adverse effects like bradycardia and extracardiac effects like hypotension and peripheral edema. So, it is usually administered orally to reduce side effects.

Diltiazem shares similarities with verapamil but tends to cause less bradycardia.

Class IV agents are commonly used to treat re-entrant supraventricular tachycardia and to decrease the ventricular rate in atrial flutter and fibrillation.