What is the prevalence of edema as a side effect with amlodipine (calcium channel blocker)?

Prevalence of Edema Side Effect with Amlodipine

Peripheral edema is a common side effect of amlodipine, occurring in approximately 10.8% of patients taking 10 mg doses and showing a clear dose-dependent relationship, with rates of 1.8% at 2.5 mg and 3.0% at 5 mg doses. 1

Incidence by Dose

• Amlodipine causes peripheral edema in a dose-dependent manner:

  • 1.8% at 2.5 mg dose 1
  • 3.0% at 5 mg dose 1
  • 10.8% at 10 mg dose 1
  • Compared to 0.6% with placebo 1

• In more recent meta-analysis data, the overall rate of edema with amlodipine was 16.6% compared to 6.2% with placebo (risk ratio: 2.9) 2

• The placebo-adjusted rate was 63%, indicating that 37% of edema cases were unrelated to amlodipine itself 2

Gender Differences

• Women experience significantly higher rates of amlodipine-induced edema than men:
  • 14.6% in women vs. 5.6% in men 1
  • This gender difference is also noted in guidelines, which state that peripheral edema is more frequent in women than men 3

Mechanism of Edema

• Amlodipine-induced edema occurs due to preferential dilation of pre-capillary vessels, which increases capillary hydrostatic pressure 4, 5
• Unlike edema from heart failure, amlodipine-induced peripheral edema is generally not associated with fluid retention or volume overload 4
• The edema typically affects the lower limbs, particularly the feet and ankles, due to gravitational effects 4

Risk Factors and Time Course

• Longer duration of amlodipine use increases edema risk, with use >5 years associated with 21.65 times higher likelihood of developing pedal edema 6
• Presence of comorbidities increases the risk of developing edema by 2.15 times 6

Management Strategies

• Dose reduction may help reduce edema while maintaining some antihypertensive effect 4
• Combining amlodipine with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can mitigate edema by causing post-capillary dilation that normalizes hydrostatic pressure 5
• Using (S)-amlodipine (the active isomer) at half the dose of conventional racemic amlodipine may provide equal antihypertensive efficacy with reduced incidence of peripheral edema (31.4% vs. 46.5%) 7

Clinical Implications

• Despite the common occurrence of edema, discontinuation of amlodipine due to adverse reactions is required in only about 1.5% of patients, similar to placebo (1%) 1
• Amlodipine is better tolerated than some other calcium channel blockers in patients with mild left ventricular dysfunction, though it should be used with caution in those with pulmonary edema or severe left ventricular dysfunction 3, 4
• Unlike verapamil and diltiazem, amlodipine has minimal effects on AV conduction and sinus node function, making it safer in certain patient populations 3, 4