Can amlodipine (calcium channel blocker) cause peripheral edema even after years of therapy?

From the Guidelines

Yes, amlodipine can cause peripheral edema even after years of being on it. This side effect is not necessarily time-limited and can develop at any point during treatment, including after long-term use. Peripheral edema from amlodipine typically affects the ankles and lower legs and occurs in approximately 5-10% of patients. The mechanism involves the medication's vasodilatory effects, which cause increased hydrostatic pressure in the capillaries, leading to fluid leakage into surrounding tissues. This side effect is dose-dependent, with higher doses (10 mg) more likely to cause edema than lower doses (2.5-5 mg) 1.

Some key points to consider:

• Amlodipine is associated with dose-related pedal edema, which is more common in women than men 1.
• If you develop edema while on amlodipine, do not stop the medication abruptly but consult your healthcare provider.
• They may consider reducing your dose, switching to another calcium channel blocker with less edema risk (like felodipine), or changing to a different class of antihypertensive medication.
• Sometimes adding an ACE inhibitor or ARB can help counteract the edema while maintaining blood pressure control.

It's essential to weigh the benefits of amlodipine against the potential risks, including peripheral edema, and to monitor patients closely for any adverse effects. The most recent guidelines and studies, such as the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, provide valuable insights into the management of hypertension and the use of calcium channel blockers like amlodipine 1.

From the FDA Drug Label

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.

Peripheral oedema is a known side effect of amlodipine, and its incidence is dose-related. The drug label reports that the incidence of peripheral oedema was 1.8% at 2.5mg, 3.0% at 5mg, and 10.8% at 10mg. Although the label does not specifically state that peripheral oedema can occur after years of being on the medication, it does mention that the adverse event profile was similar in long-term studies (CAMELOT and PREVENT). Therefore, it is possible that peripheral oedema can occur even after years of taking amlodipine 2.

From the Research

Amlodipine and Peripheral Oedema

• Amlodipine can cause peripheral oedema, even after years of being on it, as it is a common adverse effect of dihydropyridine Calcium Channel Blockers (CCB) 3, 4, 5, 6.
• The incidence of peripheral oedema with amlodipine can be reduced by using lower doses, such as 2.5-5 mg, compared to higher doses, such as 10 mg 3, 6.
• Switching to other calcium channel blockers, such as lercanidipine or lacidipine, or adding an ACE-inhibitor/angiotensin II-receptor blocker, may also help reduce the incidence of peripheral oedema 5.
• Peripheral oedema can resolve in some patients after switching from amlodipine to a combination therapy, such as amlodipine/valsartan 4.
• The exact mechanism of amlodipine-induced peripheral oedema is not fully understood, but it is thought to be related to the drug's effect on blood vessels and fluid balance in the body.

Management of Peripheral Oedema

• Reducing the dosage of amlodipine or switching to a different medication may be necessary to manage peripheral oedema 5.
• Non-pharmacologic actions, such as elevating the affected limb, or observation may be considered for mild and non-bothersome oedema 5.
• In severe cases, discontinuation of amlodipine and treatment with IV glucocorticoids and diphenhydramine may be necessary, as seen in a case report of angioedema caused by amlodipine 7.

Risk Factors and Incidence

• The risk of peripheral oedema with amlodipine is higher in patients taking higher doses, such as 10 mg, compared to lower doses, such as 2.5-5 mg 6.
• The incidence of peripheral oedema with amlodipine can be as high as 16.6% in some studies, although the placebo-adjusted rate may be lower, around 63% 6.
• Headache is also a common side effect of amlodipine, but the risk is lower with low to medium doses, and may even be reduced compared to placebo 6.