How to handle drug-induced edema

Awareness of medication-induced edema among clinicians is important to reduce unnecessary testing or treatments....

Questions come up about how to handle drug-induced edema. Peripheral edema often prompts clinicians to jump straight to a workup for thromboembolism or heart, renal, or hepatic failure. But first look for medications that can cause it...

Dihydropyridine calcium channel blockers (amlodipine, etc) cause dose-dependent edema. But it's not caused by fluid overload, so diuretics usually don't help. Red blood cells may leak into interstitial space, causing a petechial rash or skin discoloration. Try to lower the dose, or add an ACE inhibitor (lisinopril, etc) or ARB (valsartan, etc). If that doesn't work, switch to a different antihypertensive, even verapamil or diltiazem cause less edema.
Pioglitazone (Actos, etc) can cause edema, especially with higher doses (Edema is dose-dependent). Occurs in 2.5% of patients treated with 15 mg as monotherapy up to 26.1% of patients treated with 45 mg plus insulin.

Avoid pioglitazone it in patients with class 3 or 4 heart failure. In other patients, try a lower dose or switch medications. Consider trying spironolactone or hydrochlorothiazide if needed. They might help, but keep in mind they can sometimes worsen edema.

Gabapentin, pregabalin, or dopamine agonists (pramipexole, etc) can cause dose-dependent peripheral edema. Mechanism of peripheral edema may be calcium channel blockade.

With gabapentin, risk is higher with daily doses ≥ 1800 mg (7.4% vs 1.7% with doses <1800 mg/day).
With pregabalin, risk is as high as about 27% at daily doses of 300 to 600 mg. May occur within the first week of use. Try to lower the dose or switch medications. Diuretics might help some patients, but don't count on them.

References

Makani H, Bangalore S, Romero J, Wever-Pinzon O, Messerli FH. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. Am J Med. 2011 Feb;124(2):128-35. Available at: https://pubmed.ncbi.nlm.nih.gov/21295192

Epstein BJ, Roberts ME. Managing peripheral edema in patients with arterial hypertension. Am J Ther. 2009 Nov-Dec;16(6):543-53. Available at: https://pubmed.ncbi.nlm.nih.gov/19636244

Prescribing information for Actos. Takeda Pharmaceuticals America. Deerfield, IL 60015. December 2017

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