SILVER SPRING, MD — Amantadine is a prescription medication used to treat Parkinson’s disease, especially for reducing levodopa-induced dyskinesia and managing tremors. The drug works by increasing dopamine release and acting as an NMDA receptor antagonist.
Known side effects include hallucinations, dizziness, dry mouth and leg discoloration.
Now, the U.S. Food & Drug Administration is raising alarms about a possible link between the drug and corneal edema, especially in Parkinson’s patients.
A recent study published in the Journal of Neurology sought to characterize a large case series of corneal edema associated with amantadine and to disseminate the information on that safety risk.1
An FDA study team conducted a retrospective pharmacovigilance case series, searching the FDA Adverse Event Reporting System (FAERS) and the medical literature for case reports of corneal edema associated with amantadine.
After the application of corneal edema case definition criteria, case reports were assessed for a drug-event causal association between amantadine and corneal edema development.
Public health officials identified 54 cases of corneal edema reported or published since the 1990s with reasonable evidence of a causal association with amantadine prescribed for Parkinson’s disease or other neuropsychiatric indications. In those cases, the median amantadine total daily dose was 200 mg (range, 100-400 mg).
They report that corneal edema developed after a median exposure of 12 months (range, 0.6-120 months) with most cases occurring within 24 months of amantadine initiation. No apparent relationship was uncovered between reported total daily dose or exposure duration and corneal edema frequency or severity. The study also noted that the median age at corneal edema development was 61 (IQR, 50.0-64.5; range, 8-82).
“Corneal edema was bilateral in all cases,” according to the FDA. “In eight cases, corneal grafts were either performed (n = 6) or planned (n = 2). Amantadine was permanently discontinued in all but two cases where the amantadine dose was reduced, and topical corticosteroid treatment was initiated.”
The authors concluded, “Corneal edema is an important yet underrecognized safety risk associated with chronic amantadine use, particularly among patients with Parkinson’s disease. Based on our findings, the Warnings and Precautions section of the United States Prescribing Information of all amantadine products was amended.”
- Croteau, D., Tobenkin, A., Chan, V. et al. Corneal edema: an underrecognized safety risk of amantadine. J Neurol 273, 279 (2026). https://doi.org/10.1007/s00415-026-13797-y
