What are the side effects of nifedipine (calcium channel blocker)?

Side Effects of Nifedipine

The most common side effect of nifedipine is peripheral edema, which is dose-related with frequencies of 18% at 30 mg daily, 22% at 60 mg daily, and 29% at 90 mg daily compared to 10% with placebo. 1

Common Side Effects

Nifedipine's side effects can be categorized based on their mechanism and frequency:

Vasodilation-Related Effects

• Peripheral edema (most common, dose-dependent)
• Hypotension
• Dizziness
• Headache
• Flushing
• Palpitations (due to reflex tachycardia)

These vasodilatory symptoms are more prominent with nifedipine than with other calcium channel blockers like verapamil or diltiazem 2. In fact, nifedipine ranks highest among dihydropyridine calcium channel blockers in inducing peripheral edema 3.

Cardiovascular Effects

• Reflex tachycardia
• Hypotension
• Chest pain (reported in <3% of patients) 1

Unlike non-dihydropyridine calcium channel blockers (verapamil, diltiazem), nifedipine has minimal direct effects on cardiac conduction but causes potent peripheral vasodilation 4.

Gastrointestinal Effects

• Constipation (reported in <3% of patients) 1
• Nausea
• Diarrhea (in some patients) 5

Other Common Side Effects

• Leg cramps (<3%)
• Impotence (<3%)
• Urinary frequency (<3%) 1

Rare but Serious Side Effects

The FDA label reports these rare adverse events:

• Allergic hepatitis
• Alopecia
• Anaphylactic reaction
• Anemia
• Arthritis with ANA (+)
• Depression
• Erythromelalgia
• Exfoliative dermatitis
• Gingival hyperplasia
• Gynecomastia
• Hyperglycemia
• Jaundice
• Leukopenia
• Stevens-Johnson syndrome
• Syncope
• Thrombocytopenia
• Toxic epidermal necrolysis
• Transient blindness at peak plasma level 1

Special Considerations

Cardiovascular Concerns

• Nifedipine has less negative inotropic effect compared to verapamil and diltiazem, making it safer in patients with impaired left ventricular function 2
• However, it should still be avoided in patients with significantly impaired left ventricular function 4
• Immediate-release nifedipine is not recommended for unstable angina/non-ST-elevation myocardial infarction except with concomitant beta blockade due to increased risks 6

Metabolic Effects

• May inhibit insulin release in high doses, which could be relevant for diabetic patients 2
• No adverse effects on lipid or protein metabolism have been reported 2

Drug Interactions

• May increase serum digoxin levels, though the clinical significance is uncertain 5
• Can be used safely with beta-blockers, but caution is advised due to potential additive hypotensive effects 7

Risk Reduction Strategies

1. Start with lower doses in elderly patients
2. Monitor blood pressure in both sitting and standing positions to detect orthostatic changes
3. Check for peripheral edema regularly, especially in elderly patients
4. Consider combining with angiotensin-converting enzyme inhibitors to reduce the risk of peripheral edema 3
5. Avoid immediate-release formulations without concomitant beta-blockade in acute coronary syndromes 6

Comparison with Other Calcium Channel Blockers

Nifedipine (a dihydropyridine) differs from non-dihydropyridines (verapamil, diltiazem) in its side effect profile:

• Nifedipine: More vasodilatory symptoms (flushing, headache, edema), minimal effect on cardiac conduction, potential for reflex tachycardia
• Verapamil/Diltiazem: More cardiac conduction effects (bradycardia, AV block), less peripheral vasodilation, more constipation (especially with verapamil) 4, 2

Understanding these differences helps in selecting the appropriate calcium channel blocker based on patient comorbidities and tolerance.