Amlodipine Side Effects
The most common side effects of amlodipine are peripheral edema (leg/ankle swelling) and headache, which occur in a dose-dependent manner, with edema affecting up to 10.8% of patients on 10 mg daily. 1
Most Common Side Effects (Dose-Related)
The following side effects increase with higher doses of amlodipine 1:
- Peripheral edema: 1.8% at 2.5 mg, 3.0% at 5 mg, and 10.8% at 10 mg (compared to 0.6% with placebo) 1
- Headache: Common side effect, particularly noted in comparative studies 2
- Dizziness: 1.1% at 2.5 mg, 3.4% at 5 mg and 10 mg (compared to 1.5% with placebo) 1
- Flushing: 0.7% at 2.5 mg, 1.4% at 5 mg, and 2.6% at 10 mg 1
- Palpitations: 0.7% at 2.5 mg, 1.4% at 5 mg, and 4.5% at 10 mg 1
Other Common Side Effects (>1% Incidence)
Additional side effects reported more frequently than placebo include 1:
- Fatigue: 4.5% (vs. 2.8% placebo) 1
- Nausea: 2.9% (vs. 1.9% placebo) 1
- Abdominal pain: 1.6% (vs. 0.3% placebo) 1
- Somnolence: 1.4% (vs. 0.6% placebo) 1
Gender-Specific Differences
Women experience significantly higher rates of certain vasodilatory side effects compared to men 1:
- Edema: 14.6% in women vs. 5.6% in men 1
- Flushing: 4.5% in women vs. 1.5% in men 1
- Palpitations: 3.3% in women vs. 1.4% in men 1
Less Common Side Effects (<1% but >0.1%)
The following adverse events have been reported but occur rarely 1:
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
Dermatologic
- Angioedema, erythema multiforme, pruritus, rash (erythematous and maculopapular) 1
Other Systems
- Sexual dysfunction, insomnia, nervousness, depression, dyspnea, abnormal vision, micturition frequency 1
Important Clinical Considerations
Mechanism of Vasodilatory Side Effects
The edema, flushing, and headache associated with amlodipine result from its potent peripheral arterial vasodilatory effects, which are characteristic of dihydropyridine calcium channel blockers 2. These effects are generally mild to moderate in severity and related to the drug's mechanism of action 3.
Tolerability Profile
- Discontinuation due to adverse effects occurs in only approximately 1.5% of patients, which is not significantly different from placebo 1
- Amlodipine is generally well tolerated, with most side effects being mild or moderate 1, 4
- The gradual onset of action and long half-life (35-50 hours) contribute to better tolerability compared to short-acting dihydropyridines like immediate-release nifedipine 5
Metabolic and Laboratory Effects
Amlodipine has not been associated with clinically significant changes in routine laboratory tests 1. Specifically, no adverse effects have been observed on 1, 4:
- Serum potassium, glucose, or lipid profiles
- Total triglycerides or cholesterol levels
- Uric acid, blood urea nitrogen, or creatinine
Rare Postmarketing Effects
Gynecomastia has been reported infrequently in postmarketing surveillance, though a causal relationship is uncertain 1.
Critical Safety Note
Unlike immediate-release nifedipine, amlodipine does not cause reflex tachycardia or rapid blood pressure drops, making it safer for use without concurrent beta-blocker therapy 2, 5. However, systemic hypotension remains a potential concern, particularly in patients with heart failure or severe left ventricular dysfunction 2.