How to treat peripheral edema due to dihydropyridine calcium channel blockers

One of the most ADVERSE EFFECT caused by calcium channel blockers (CCD), dihydropyridine (e.g., amlodipine, etc) is peripheral edema. It's dose-dependent. Incidence of peripheral edema may be > 80% with high doses. Major cause of CCB nonadherence. Mechanism is thought to be arteriolar dilatation. The resulting pressure gradient between arteriole and venule capillaries pushes fluid into the interstitial space. Red blood cells may leak into interstitial space, causing a petechial rash or skin discoloration.

Questions often come up about how to handle peripheral edema due to dihydropyridine calcium channel blockers (amlodipine, etc). These often cause edema especially at higher doses. It's not due to fluid overload, so diuretics usually don't help.

• Try lowering the dose. Most of the antihypertensive effect is at lower doses, so cutting the dose in half doesn't also cut the blood pressure benefit in half.
• Or try ADDING an ACE inhibitor or ARB to counteract the edema and augment the antihypertensive effect.
• Switch to a different antihypertensive, if needed. Verapamil or diltiazem is less likely to cause edema than a dihydropyridine.
• Watch for drugs that can increase dihydropyridine levels and, therefore, the risk of edema. For example, amlodipine levels can be increased by strong 3A4 inhibitors (clarithromycin, etc).

References

• Makani, H., Bangalore, S., Romero, J., Wever-Pinzon, O. and Messerli, F.H. (2011). Effect of Renin-Angiotensin System Blockade on Calcium Channel Blocker-Associated Peripheral Edema. The American Journal of Medicine, [online] 124(2), pp.128–135. Available at: https://www.amjmed.com/article/S0002-9343(10)00745-X/fulltex

  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