Amlodipine Side Effects
Amlodipine's most common side effects are peripheral edema (occurring in 10.8% at 10mg dose), headache, flushing, and dizziness, with edema being dose-related and more frequent in women. 1
Most Common Side Effects (Dose-Related)
The FDA-approved labeling from controlled trials demonstrates clear dose-dependent adverse effects 1:
- Peripheral edema: 1.8% (2.5mg), 3.0% (5mg), 10.8% (10mg) vs 0.6% placebo
- Dizziness: 1.1% (2.5mg), 3.4% (5mg), 3.4% (10mg) vs 1.5% placebo
- Flushing: 0.7% (2.5mg), 1.4% (5mg), 2.6% (10mg) vs 0% placebo
- Palpitations: 0.7% (2.5mg), 1.4% (5mg), 4.5% (10mg) vs 0.6% placebo
Important caveat: Meta-analysis data reveals that approximately 37% of edema cases occurring on amlodipine may be unrelated to the drug itself, with the placebo-adjusted rate being 63%. 2
Common Non-Dose-Related Side Effects
Additional adverse effects occurring in >1% of patients include 1:
- Fatigue: 4.5% vs 2.8% placebo
- Nausea: 2.9% vs 1.9% placebo
- Abdominal pain: 1.6% vs 0.3% placebo
- Somnolence: 1.4% vs 0.6% placebo
The American College of Cardiology confirms headache, flushing, and dizziness as additional potential side effects. 3
Gender-Specific Differences
Women experience significantly higher rates of certain side effects compared to men 1:
- Edema: 14.6% in women vs 5.6% in men (on amlodipine)
- Flushing: 4.5% in women vs 1.5% in men
- Palpitations: 3.3% in women vs 1.4% in men
Less Common But Clinically Important Side Effects
Occurring in <1% but >0.1% of patients 1:
Cardiovascular: Arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis
Neurological: Hypoesthesia, peripheral neuropathy, paresthesia, tremor, vertigo
Gastrointestinal: Anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia
Dermatologic: Angioedema, erythema multiforme, pruritus, rash (various types)
Hematologic: Leukopenia, purpura, thrombocytopenia
Serious Cardiovascular Considerations
Major side effects include hypotension, worsening heart failure, bradycardia, and AV block, as noted by the American Heart Association. 4
The European Society of Cardiology warns that all calcium channel blockers may precipitate heart failure in predisposed patients. 3 The American College of Cardiology recommends monitoring closely for signs of worsening heart failure, including increased dyspnea, weight gain, or edema. 5
Critical pitfall: Amlodipine should not be used as routine treatment for heart failure with reduced ejection fraction (HFrEF), though it may be considered for concurrent hypertension or angina as it has neutral effects on mortality. 5
Dose-Reduction Strategy for Side Effect Management
Using low to medium doses (2.5-5mg) significantly reduces side effect burden 2:
- Lower rates of edema with 2.5-5mg (risk ratio: 2.01) compared to 10mg (risk ratio: 3.08)
- Headache is actually reduced on amlodipine at low/medium doses (risk ratio: 0.52) vs placebo
Drug Interactions and Precautions
The American Heart Association warns that NSAIDs should be avoided in patients taking amlodipine for hypertension, as they worsen blood pressure control and may precipitate heart failure. 5
The American College of Cardiology advises against combining amlodipine with non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in heart failure patients, as these agents cause myocardial depression. 5
Overdose Management
In cases of amlodipine overdose, the American Heart Association recommends calcium administration, vasopressors, and high-dose insulin therapy may be required for severe toxicity. 5
Laboratory and Metabolic Effects
Amlodipine has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, glucose, triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine. 1