What are the adverse effects of Calcium Channel Blockers (CCBs)?

From the Guidelines

Calcium channel blockers (CCBs) are known to cause several adverse effects, with the most common being peripheral edema, headaches, dizziness, flushing, and constipation, as reported in the 2013 guidelines 1. The severity and type of side effects vary depending on the specific CCB used, with dihydropyridines (such as amlodipine and nifedipine) causing more peripheral vasodilation effects, and non-dihydropyridines (such as verapamil and diltiazem) having stronger cardiac effects, including heart rate slowing and heart block 1. Some key points to consider when prescribing CCBs include:

• Peripheral edema is a common side effect, especially with dihydropyridines, and can be managed with dosage adjustments or concomitant therapy 1.
• Hypotension is a potential side effect, especially when starting therapy or increasing doses, and can lead to dizziness or fainting 1.
• CCBs can cause gastrointestinal disturbances, such as nausea or gastroesophageal reflux, and patients should be monitored for these side effects 1.
• Gingival hyperplasia can occur with long-term use of certain CCBs, such as nifedipine, and patients should be advised to maintain good oral hygiene 1. It is essential to carefully select the type and dose of CCB based on the individual patient's needs and medical history, and to monitor for potential side effects, as recommended in the 2013 guidelines 1. Additionally, the 2007 scientific statement from the American Heart Association provides further insight into the mechanisms of CCBs and their effects on the cardiovascular system 1. However, the most recent and highest quality study, the 2013 guidelines 1, should be prioritized when making clinical decisions. In summary, CCBs can cause a range of adverse effects, and careful patient selection, dosing, and monitoring are necessary to minimize these risks and optimize treatment outcomes, as emphasized in the 2013 guidelines 1.

From the FDA Drug Label

Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume In hemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when coadministered with beta-blockers to man. Overdose with verapamil may lead to pronounced hypotension, bradycardia, and conduction system abnormalities (e.g., junctional rhythm with AV dissociation and high degree AV block, including asystole). Verapamil hydrochloride does not alter total serum calcium levels.

Adverse effects of calcium channel blockers include:

• Negative inotropic effects (although not seen in intact animals at therapeutic doses)
• Hypotension
• Bradycardia
• Conduction system abnormalities However, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man. Verapamil can lead to pronounced hypotension, bradycardia, and conduction system abnormalities in cases of overdose. 2 3 3

From the Research

Adverse Effects of Calcium Channel Blockers

• Peripheral edema is a common adverse effect of calcium channel blockers (CCBs), occurring in 10.7% of patients compared to 3.2% in controls/placebo 4
• The incidence of peripheral edema increases with the duration of therapy, reaching 24% after 6 months, and is higher with dihydropyridine CCBs (12.3%) compared to non-dihydropyridine CCBs (3.1%) 4
• High-dose CCBs are associated with a higher incidence of peripheral edema (16.1%) compared to low-dose CCBs (5.7%) 4
• Other adverse effects of CCBs include headache, flushing, and tachycardia, particularly with high doses of dihydropyridine CCBs 5
• Nondihydropyridine CCBs, such as verapamil, can cause constipation as a side effect 5
• The risk of peripheral edema is lower with newer, lipophilic dihydropyridine CCBs, such as amlodipine, compared to traditional dihydropyridine CCBs 4

Comparison of Adverse Effects among Different Types of CCBs

• Dihydropyridine CCBs, such as nifedipine and amlodipine, are more likely to cause peripheral edema and headache compared to non-dihydropyridine CCBs, such as verapamil and diltiazem 4, 5
• Nondihydropyridine CCBs, such as verapamil, are more likely to cause constipation and have a negative inotropic effect compared to dihydropyridine CCBs 5, 6
• Newer, lipophilic dihydropyridine CCBs, such as lacidipine and lercanidipine, may have a lower incidence of peripheral edema and other adverse effects compared to traditional dihydropyridine CCBs 7

Clinical Implications of Adverse Effects

• The adverse effects of CCBs can impact patient compliance and quality of life, particularly if they are severe or persistent 4, 5
• The choice of CCB should be individualized based on the patient's clinical profile, including the presence of comorbidities and the risk of adverse effects 5, 6
• Healthcare providers should monitor patients for adverse effects and adjust the treatment regimen as needed to minimize the risk of adverse effects and optimize therapeutic outcomes 4, 5