From the Guidelines
Medications that can cause leg swelling include calcium channel blockers, such as amlodipine and nifedipine, which are associated with dose-related pedal edema, as noted in the 2018 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. These medications typically cause swelling by altering kidney function, affecting blood vessel permeability, or disrupting the body's sodium and water balance. Some key points to consider:
- Blood pressure medications, including ACE inhibitors (lisinopril, enalapril) and beta-blockers (metoprolol), can also cause fluid retention and leg swelling.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen are known to cause fluid retention.
- Hormonal medications, including estrogen-containing contraceptives, hormone replacement therapy, and testosterone supplements, frequently cause edema.
- Diabetes medications like thiazolidinediones (pioglitazone, rosiglitazone) are associated with this side effect.
- Steroids, such as prednisone, antidepressants (particularly MAOIs and tricyclics), and certain chemotherapy drugs also commonly cause swelling. It's essential to note that the swelling usually develops gradually and affects both legs symmetrically. If you experience sudden or severe swelling, especially in one leg only, seek medical attention immediately as this could indicate a blood clot rather than medication-related edema. Elevating your legs, reducing salt intake, and staying physically active may help reduce medication-induced swelling, but never stop taking prescribed medications without consulting your healthcare provider, as supported by various studies, including those published in Circulation 1 and Nature Reviews Cardiology 1.
From the FDA Drug Label
Edema 1.8 3.0 10.8 0.6
For several adverse experiences that appear to be drug and dose related, there was a greater incidence in women than men associated with amlodipine treatment as shown in the following table: Amlodipine Placebo Male=% (N=1218) Female=% (N=512) Male=% (N=914) Female=% (N=336) Edema 5.6 14.6 1.4 5.1
Medications that can cause leg swelling include:
- Amlodipine 2 Key points:
- Edema is a possible side effect of amlodipine, with a higher incidence in women (14.6%) compared to men (5.6%).
- The incidence of edema increases with dose, ranging from 1.8% at 2.5mg to 10.8% at 10mg.
From the Research
Medications that Cause Leg Swelling
Medications that can cause leg swelling include:
- Dihydropyridine calcium channel blockers, such as nifedipine and amlodipine 3, 4, 5, 6, 7
- Thiazolidinediones (TZDs) 3
- Neuropathic pain agents 3
- Dopamine agonists 3
- Antipsychotics 3
- Nitrates 3
- Nonsteroidal anti-inflammatory drugs (NSAIDs) 3
- Steroids 3
- Angiotensin-converting enzyme (ACE) inhibitors 3
- Insulin 3
Mechanisms of Edema
The mechanisms by which these medications cause edema include:
- Increased hydrostatic pressure 3, 6
- Selective pre-capillary vessel vasodilation 3
- Increased vascular permeability 3
- Stimulation of peroxisome proliferator-activated receptor gamma (PPARγ) 3
- Increased vascular endothelial growth factor (VEGF) secretion 3
- Renal sodium and fluid retention 3
Reducing the Risk of Edema
The risk of edema can be reduced by:
- Combining dihydropyridine calcium channel blockers with renin-angiotensin system blockers, such as ACE inhibitors or angiotensin receptor blockers (ARBs) 4, 5, 6
- Using lipophilic dihydropyridine calcium channel blockers instead of traditional dihydropyridines 7
- Using non-dihydropyridine calcium channel blockers instead of dihydropyridines 7
- Using low-dose calcium channel blockers instead of high-dose 7