General Side Effects of Amlodipine
The most common side effects of amlodipine include peripheral edema, dizziness, flushing, fatigue, and palpitations, with edema being particularly prevalent at higher doses and more common in women than men. 1
Common Side Effects
- Edema (swelling of legs or ankles) occurs in a dose-dependent manner, ranging from 1.8% at 2.5mg to 10.8% at 10mg doses, compared to 0.6% with placebo 1
- Dizziness (1.1-3.4% vs 1.5% with placebo) 1
- Flushing (0.7-2.6% vs 0% with placebo) 1
- Palpitations (0.7-4.5% vs 0.6% with placebo) 1
- Fatigue (4.5% vs 2.8% with placebo) 1
- Nausea (2.9% vs 1.9% with placebo) 1
- Abdominal pain (1.6% vs 0.3% with placebo) 1
- Somnolence (1.4% vs 0.6% with placebo) 1
Gender Differences in Side Effects
Amlodipine side effects show notable gender differences, with women experiencing higher rates of certain adverse effects 1:
- Edema: 14.6% in females vs 5.6% in males 1
- Flushing: 4.5% in females vs 1.5% in males 1
- Palpitations: 3.3% in females vs 1.4% in males 1
- Somnolence: 1.6% in females vs 1.3% in males 1
Less Common Side Effects (<1% incidence)
- Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis 1
- Neurological: hypoesthesia, peripheral neuropathy, paresthesia, tremor, vertigo 1
- Gastrointestinal: anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia 1
- Musculoskeletal: arthralgia, arthrosis, muscle cramps, myalgia 1
- Psychiatric: sexual dysfunction (male and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization 1
- Dermatological: angioedema, erythema multiforme, pruritus, rash 1
- Special senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus 1
Pharmacological Considerations
- Amlodipine is a dihydropyridine calcium channel blocker with pronounced peripheral arterial dilatory effects 2, 3
- Unlike non-dihydropyridine calcium channel blockers (verapamil and diltiazem), amlodipine has minimal effects on cardiac conduction, atrioventricular node function, and sinus node function 2
- Amlodipine is generally well-tolerated by patients with mild left ventricular dysfunction, unlike verapamil and diltiazem which should be avoided in patients with pulmonary edema or severe left ventricular dysfunction 3
Important Clinical Cautions
- Rapid-release, short-acting dihydropyridines (like nifedipine) must be avoided without concomitant beta-blockade due to increased adverse potential, though this is less of a concern with long-acting amlodipine 2, 3
- In patients with heart failure with reduced ejection fraction (HFrEF), dihydropyridine calcium channel blockers including amlodipine are not recommended as routine treatment 2
- Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) are contraindicated in patients with HFrEF due to their negative inotropic effects 2
- Amlodipine may be considered for management of hypertension or ischemic heart disease in patients with heart failure as it is generally well-tolerated and had neutral effects on morbidity and mortality in large randomized controlled trials 2
Laboratory Effects
- Amlodipine therapy has not been associated with clinically significant changes in routine laboratory tests 1
- No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine 1
Postmarketing Experience
- Gynecomastia has been reported infrequently in postmarketing surveillance, though a causal relationship is uncertain 1
- In pediatric patients, amlodipine-related generalized edema has been reported, though the incidence appears lower than in adults 4
When prescribing amlodipine, it's important to monitor for peripheral edema, especially at higher doses and in female patients, as this is the most common reason for discontinuation of therapy 1, 5.