Bilateral Lower Extremity Edema During Donepezil Treatment: A Case Report

Introduction/ Background: Acute bilateral lower-extremity edema is uncommon and often results from medication side effects, acute heart failure, nephrotic syndrome, or bilateral deep vein thrombosis. Drugs such as dihydropyridine calcium channel blockers, corticosteroids, thiazolidinediones, and nonsteroidal anti-inflammatory agents are known to cause edema. Donepezil, a widely used acetylcholinesterase inhibitor for Alzheimer's disease, has not been previously linked to leg edema. Recognizing rare adverse reactions is essential for patient safety, as edema may indicate serious conditions. Case Presentation: A 75-year-old woman with Alzheimer's disease developed bilateral pitting lower leg edema six months after starting treatment with donepezil. She had no history of cardiac, renal, hepatic, or venous diseases. Laboratory tests, electrocardiography, chest X-ray, and computed tomography venogram were normal, except for mild anemia and a slightly reduced estimated glomerular filtration rate. The edema resolved three weeks after discontinuation and did not recur after the administration of rivastigmine. Conclusion: The temporal association and resolution upon drug cessation suggest a probable association. Possible mechanisms may include cholinergic-induced vasodilation, which increases capillary permeability.