Amantadine is a fascinating molecule, originally approved by the FDA to treat viral infections, a use that continues to this day.

Amantadine

It has also been commonly used to treat Parkinson’s disease, although until recently, existing clinical trials provided only weak evidence for their use, and the mechanism by which it benefits Parkinson’s patients remains poorly understood.  Somewhat confusingly, an immediate-release version called Symmetrel is approved for treating symptoms of Parkinson’s disease, while an extended-release version called Gocovri was recently approved (2017) for treating dyskinesias resulting from levodopa treatment.  Both have some pretty gnarly side effects, such as hallucination (21% on Gocovri vs. 3% on placebo, see Table 1) and, more rarely (~2%) suicidal ideation; in addition, overdoses are a concern, and sudden discontinuation is to be avoided.  In clinical trials, Gocovri showed significant increases in on-time without dyskinesias (~2-3 hours improvement), and significant decreases in off-time (~1 hour) after 12 weeks of treatment.

In 2018, another extended-release formulation, Osmolex ER, was approved by the FDA.  Making the situation even more confusing, Osmolex is approved for Parkinson’s symptoms, based on demonstrating its bioequivalence to immediate release amantadine, but not specifically for dyskinesias (because it has not been tested for this indication, or directly compared to Gocovri).  Gocovri appears to be absorbed somewhat more slowly than Osmolex ER, 12 vs. 7.5 hours to peak concentration.