What medications can cause edema?

Medications That Can Cause Edema

Numerous medications can cause edema through various mechanisms including increased capillary permeability, sodium/water retention, vasodilation, and other pathways. The following is a comprehensive list of medications known to cause edema, organized by drug class and mechanism.

Cardiovascular Medications

Calcium Channel Blockers

• Dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) are associated with dose-related pedal edema, which is more common in women than men 1
• Mechanism: Selective precapillary vasodilation causing increased hydrostatic pressure 2
• Amlodipine specifically shows dose-dependent edema rates: 1.8% at 2.5mg, 3.0% at 5mg, and 10.8% at 10mg 3

Vasodilators

• Cause edema through increased capillary permeability from vasodilation 1
• Nitrates can cause edema through vasodilatory effects 4

ACE Inhibitors/ARBs

• Can cause angioedema (a medical emergency when involving the larynx) 4
• Paradoxically, ACE inhibitors can help reduce edema caused by calcium channel blockers 2

Alpha-Adrenergic Blockers

• Cause edema through vasodilation and increased capillary permeability 1

Antidiabetic Medications

Thiazolidinediones (TZDs)

• Rosiglitazone and pioglitazone cause significant fluid retention 1
• Edema incidence: 3-5% as monotherapy, higher (4.8-7.5%) when combined with other agents 1
• Risk factors include: heart failure history, coronary artery disease, hypertension, advanced age, long-standing diabetes, and insulin coadministration 1
• Mechanism: PPARγ stimulation increases vascular permeability and renal sodium retention 4
• Edema risk is highest when combined with insulin 1

Insulin

• Can cause edema through increased capillary permeability 4

Anti-inflammatory Medications

NSAIDs

• Cause edema through sodium/water retention and renal mechanisms 1, 5
• Can worsen existing heart failure through fluid retention 6

Corticosteroids

• Cause sodium retention with resultant edema and potassium loss 7
• Should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency 7
• Mechanism includes increased plasma volume through sodium/water retention 1

Neurologic/Psychiatric Medications

Antiepileptics

• Cause edema through various mechanisms including increased capillary permeability 1

Antidepressants

• Associated with edema through multiple mechanisms 1

Antipsychotics

• Can cause peripheral edema through various mechanisms 1, 4

Dopamine Agonists

• Can cause peripheral edema 4

Hormone Therapies

Hormone Replacement Therapy

• Estrogen and progesterone therapies can cause edema 1

Other Medications

Chemotherapy Agents

• Various chemotherapeutic agents can cause edema through increased capillary permeability 1
• Some agents like pemetrexed may cause erythematous edema 8

Immunosuppressants

• Sirolimus (mTOR inhibitor) can cause unilateral edema 8

Management of Drug-Induced Edema

General Approaches

• Identify and discontinue or reduce the causative medication when possible 5
• Sodium restriction and appropriate diuretic therapy 6
• Leg elevation may be helpful in some patients 6

Specific Interventions

• For calcium channel blocker-induced edema: Consider adding an ACE inhibitor or ARB 1, 2
• For TZD-induced edema: Consider dose reduction or discontinuation if severe; loop diuretics may have variable effectiveness 1
• For corticosteroid-induced edema: Use lowest possible effective dose 7

Special Considerations

Monitoring Recommendations

• For patients on TZDs: Monitor for weight gain and pedal edema, especially within the first few months of therapy 1
• For patients on dihydropyridine calcium channel blockers: Be alert for early signs of edema, especially in women who are at higher risk 3

Risk Factors for Severe Edema

• Concurrent use of multiple edema-causing medications 1
• Pre-existing heart failure, renal insufficiency, or hepatic disease 1
• Advanced age and female gender for certain medications (e.g., calcium channel blockers) 3

By understanding the mechanisms and risk factors for drug-induced edema, clinicians can better prevent, identify, and manage this common medication side effect.