Does amlodipine cause peripheral edema (swelling of the ankles)?

Amlodipine and Ankle Swelling

Yes, amlodipine commonly causes peripheral edema (swelling of the ankles) as a well-documented side effect. 1

Mechanism and Prevalence

Amlodipine, a dihydropyridine calcium channel blocker (CCB), causes peripheral edema through:

• Preferential dilation of arterioles without corresponding venous dilation
• Increased hydrostatic pressure in capillaries
• Fluid extravasation into interstitial tissues

According to the FDA drug label, peripheral edema occurs in a dose-dependent manner 1:

• 1.8% at 2.5mg dose
• 3.0% at 5mg dose
• 10.8% at 10mg dose (compared to 0.6% with placebo)

The incidence is significantly higher in women (14.6%) than men (5.6%) 1.

Clinical Presentation

The edema typically:

• Is dose-dependent
• Affects the lower extremities (ankles) most commonly
• Is not associated with heart failure or renal dysfunction
• May worsen with prolonged standing
• Usually resolves upon discontinuation of the medication

Management Options

1. Dose reduction: Consider lowering the dose if blood pressure control allows 2

2. Alternative formulations: (S)-amlodipine (the active enantiomer) at half the dose of conventional racemic amlodipine may provide equal antihypertensive efficacy with reduced incidence of peripheral edema 3

3. Combination therapy: Adding an ACE inhibitor or ARB may reduce the severity of amlodipine-induced edema 4

4. Alternative antihypertensives: Consider switching to:

   • ACE inhibitors or ARBs as first-line alternatives 5
   • Thiazide diuretics 5
   • Beta-blockers (if no contraindications)

Special Considerations

• Rare presentations: While ankle edema is most common, rare cases of upper extremity edema 6 and even anasarca (generalized edema) 7 have been reported

• Heart failure patients: Amlodipine can be used in heart failure patients if required, despite the edema risk, unlike non-dihydropyridine CCBs (verapamil, diltiazem) which are contraindicated in heart failure with reduced ejection fraction 5

• Monitoring: Regular assessment for peripheral edema should be part of follow-up for patients on amlodipine

Conclusion

Peripheral edema is a common, dose-dependent side effect of amlodipine that may necessitate dose adjustment or medication change in some patients. The edema is not associated with cardiac, hepatic, or renal dysfunction and typically resolves upon discontinuation of the medication.