Non-dihydropyridine CCBs (verapamil and diltiazem) are contraindicated in patients with certain cardiovascular conditions due to their negative effects on heart rate and contractility. They should not be used in patients with heart failure with reduced ejection fraction (HFrEF), as they can worsen cardiac output. These agents are also contraindicated in individuals with second or third-degree AV block without a pacemaker, systolic blood pressure less than 90 mmHg, sick sinus syndrome, and atrial fibrillation or flutter conducted over an accessory pathway (Wolff-Parkinson-White syndrome), where AV nodal block can accelerate conduction down the bypass tract and precipitate ventricular fibrillation. Combining verapamil or diltiazem with a beta-blocker or digoxin is not an absolute contraindication but adds nodal depression and is a common route to symptomatic bradycardia and heart block, especially in older patients. The risk of bradycardia and AV block is heightened in these populations, and these drugs can exacerbate existing conduction abnormalities.
Additionally, CCBs are contraindicated in patients with known hypersensitivity to the drugs or their components. Severe hypotension and severe aortic stenosis are class-wide contraindications. Immediate-release nifedipine is contraindicated in acute coronary syndromes, where its abrupt vasodilation and reflex tachycardia increased mortality in older trials. In heart failure with reduced ejection fraction, verapamil, diltiazem, and nifedipine worsen outcomes, while amlodipine and felodipine were neutral in randomized trials and are the only CCBs that can be continued there when needed for angina or blood pressure. Clevidipine is additionally contraindicated with allergy to soy or egg products and in disorders of lipid metabolism because it is a lipid emulsion. Dermatologic reactions, such as Stevens-Johnson syndrome and erythema multiforme, can also occur. Lastly, CCBs should be used cautiously in patients with renal or hepatic impairment, as drug clearance may be reduced, increasing the risk of toxicity. Dose adjustment or close monitoring is often recommended in such cases.
