Does amlodipine (calcium channel blocker) cause peripheral edema (ankle swelling)?

From the Guidelines

Amlodipine is known to cause peripheral edema, particularly ankle swelling, in a significant number of patients, with an incidence rate of approximately 5-10% at standard doses. This side effect is dose-dependent and typically develops within the first few weeks of starting treatment 1. The mechanism involves the drug's vasodilatory effect on arterioles without corresponding venous dilation, creating a pressure imbalance that forces fluid into surrounding tissues. Some key points to consider about amlodipine-induced peripheral edema include:

• It is not harmful but can be uncomfortable and may affect medication adherence.
• Management options include leg elevation, reducing salt intake, taking the medication at bedtime, or discussing with your doctor about lowering the dose or switching to another antihypertensive medication.
• Unlike edema caused by heart failure, this side effect doesn't indicate worsening of cardiovascular disease and doesn't typically respond well to diuretics.
• The incidence of pedal edema is more common in women than men, as noted in the guidelines for the prevention, detection, evaluation, and management of high blood pressure in adults 1. It's essential to weigh the benefits of amlodipine in managing hypertension against the potential for peripheral edema and to discuss management strategies with your doctor if this side effect occurs.

From the FDA Drug Label

In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to 10 mg to placebo (N=1250), the incidence (%) of side effects that occurred in a dose related manner are as follows: 2.5mg N=275 Amlodipine 5mg N=296 10mg N=268 Placebo N=520 Edema 1.8 3.0 10.8 0.6 ... The following events occurred in <1% but >0. 1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: ... In the CAMELOT and PREVENT studies [see Clinical Studies (14.4)] , the adverse event profile was similar to that reported previously (see above), with the most common adverse event being peripheral edema.

Amlodipine besylate may cause the following side effects Most side effects are mild or moderate: swelling of your legs or ankles

Amlodipine can cause ankle swelling, also known as peripheral edema. The incidence of edema in clinical trials was dose-related, with higher doses of amlodipine associated with a higher incidence of edema. In the clinical trials, the incidence of edema was 1.8% at 2.5mg, 3.0% at 5mg, and 10.8% at 10mg, compared to 0.6% with placebo 2. Additionally, swelling of the legs or ankles is listed as a possible side effect of amlodipine besylate 2.

From the Research

Amlodipine and Ankle Swelling

• Amlodipine, a calcium channel blocker, has been associated with peripheral edema, including ankle swelling, in several studies 3, 4, 5, 6, 7.
• The exact mechanism of amlodipine-induced edema is not fully understood, but it is thought to be related to increased capillary hydrostatic pressure due to preferential dilation of pre-capillary vessels 6.
• Studies have shown that the incidence of edema is higher with amlodipine compared to other calcium channel blockers, such as lacidipine 4.
• The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in combination with amlodipine may help mitigate edema by normalizing hydrostatic pressure 6.
• Amlodipine has been shown to cause dependent leg edema in essential hypertension, which can be attenuated by the use of ACEIs or ARBs 7.

Incidence of Edema

• A study found that 25% of patients who received amlodipine 10 mg per day experienced edema 6.
• Another study found that edema occurred more frequently with amlodipine (15/32) compared to lacidipine (6/30) 4.
• A case report described a patient who developed anasarca edema, a rare but severe form of edema, after starting amlodipine treatment 5.

Management of Edema

• Discontinuation of amlodipine has been shown to resolve edema in some cases 3, 5.
• The use of ACEIs or ARBs in combination with amlodipine may help prevent or reverse edema 6, 7.
• Close monitoring of patients for signs of edema and adjusting treatment as needed is important for managing this potential side effect.