Can any of these medications cause swelling of the hands and feet?

Medications That Can Cause Swelling of Hands and Feet

Yes, several medications in this list can cause swelling of the hands and feet, with risperidone, losartan, and diclofenac being the most likely culprits that require immediate attention.

Primary Offenders

Risperidone (0.5 mg twice daily)

• Risperidone has a well-documented association with peripheral edema, including swelling of the lower limbs, hands, and feet 1
• When edema develops on risperidone, systemic causes (renal, hepatic, cardiac dysfunction) must be ruled out first before attributing it to the medication 1
• If risperidone is the cause, the medication should be suspended for 1 week to observe resolution of edema 1
• Alternative antipsychotics to consider include haloperidol, aripiprazole, lurasidone, or ziprasidone 1

Losartan (25 mg daily)

• The FDA label specifically lists hypotension and orthostatic hypotension as adverse effects occurring with ≥2% difference versus placebo 2
• Angioedema, including swelling of the face, lips, pharynx, tongue, larynx, and extremities, has been reported in postmarketing experience 2
• ACE inhibitors and angiotensin receptor blockers (ARBs) like losartan can cause bradykinin-mediated angioedema, which may occur years after initiating treatment 3

Diclofenac (1% topical gel, 4 times daily)

• NSAIDs induce edema through sodium/water retention and renal dysfunction mechanisms 4
• Drug-induced peripheral edema from NSAIDs involves precapillary arteriolar vasodilation and sodium retention 5
• Even topical NSAIDs can cause systemic absorption sufficient to produce edema, particularly with frequent application 6

Secondary Considerations

Atorvastatin (20 mg daily)

• The FDA label does not list edema as a common adverse effect 7
• Statins are not typically associated with peripheral edema 6

Divalproex ER (1000 mg at bedtime)

• Peripheral edema is not a prominent adverse effect of valproate medications 6

Aspirin (325 mg PRN)

• As an NSAID, aspirin can theoretically cause edema through sodium retention, though this is more common with chronic use at higher doses 4

Clinical Approach

Immediate evaluation should include:

• Assessment for bilateral versus unilateral swelling (unilateral suggests alternative diagnosis like DVT)
• Examination for pitting versus non-pitting edema
• Cardiovascular examination for signs of heart failure 8
• Renal function tests (creatinine, BUN) 1
• Hepatic function tests 1
• Review timing of edema onset relative to medication initiation 3

Management algorithm:

1. If edema is acute and involves face/lips/tongue: Consider angioedema from losartan—this is a medical emergency requiring immediate discontinuation and emergency care 2, 3
2. If edema is bilateral lower extremity/hands: Suspect risperidone first given its clear association—hold medication for 1 week and monitor 1
3. If edema persists after risperidone discontinuation: Consider diclofenac as the culprit and discontinue topical NSAID 5
4. Rule out systemic causes: Check for heart failure, renal insufficiency, hepatic dysfunction, and venous insufficiency before attributing to medications 1, 8

Critical Pitfalls to Avoid

• Do not assume topical medications cannot cause systemic effects—topical diclofenac with frequent application (4 times daily) can achieve systemic levels sufficient to cause edema 6
• Do not overlook risperidone as a cause—antipsychotics are frequently missed as edema culprits despite clear evidence 1
• Do not continue losartan if angioedema develops—this can progress to life-threatening airway obstruction 2, 3
• Avoid prescribing cascade—do not add diuretics without first identifying and discontinuing the causative medication 5