Section 03 · Monograph

Amantadine

Reviewed Nov 2026FDA label

Gocovri ER / generic IRNMDA antagonist/dopaminergic

Indications

Gocovri (extended-release amantadine): treatment of dyskinesia in Parkinson's disease patients receiving levodopa-based therapyFDA-labeled
Gocovri: adjunctive treatment to levodopa/carbidopa in Parkinson's disease patients experiencing 'off' episodesFDA-labeled
Immediate-release amantadine HCl: treatment of idiopathic Parkinson's disease, postencephalitic parkinsonism, and symptomatic parkinsonism (e.g., post-CO poisoning, cerebral arteriosclerosis-related)FDA-labeled
Immediate-release amantadine HCl: treatment of drug-induced extrapyramidal reactionsFDA-labeled

Weak, uncompetitive (non-competitive) antagonist of the NMDA-type glutamate receptor
Also increases dopamine release and blocks dopamine reuptake at nerve terminals, contributing to antiparkinsonian effect
Exact mechanism underlying reduction of levodopa-induced dyskinesia is not fully established but is believed related to NMDA receptor antagonism in the basal ganglia
Exhibits some anticholinergic-like clinical effects despite minimal direct anticholinergic receptor activity in preclinical models

Gocovri ER: initiate 137 mg once daily at bedtime; increase to maintenance dose of 274 mg once daily after 1 week
Gocovri capsules may be swallowed whole or opened and sprinkled on soft food; take with or without food
Immediate-release amantadine for PD: typically 100 mg twice daily when used as monotherapy; benefit may appear within 48 hours
IR amantadine: patients on high doses of other antiparkinsonian drugs or with serious illness should start at 100 mg once daily, increasing to twice daily after 1–several weeks
IR amantadine: doses up to 400 mg/day in divided doses have been used in patients with suboptimal response, under close supervision
Avoid abrupt discontinuation of either formulation — taper gradually to reduce risk of a neuroleptic-malignant-syndrome-like withdrawal reaction

Gocovri renal dosing: moderate impairment requires reduced dose (68.5–137 mg); severe impairment maximum 68.5 mg once daily; contraindicated in end-stage renal disease

Known hypersensitivity to amantadine or any component of the formulation
Gocovri specifically contraindicated in end-stage renal disease (CrCl < 15 mL/min/1.73 m²)

Additive CNS/anticholinergic effects with other anticholinergic drugs — reduce dose if atropine-like effects (confusion, hallucinations) occur
Urinary alkalinizing agents (e.g., carbonic anhydrase inhibitors, some antacids) can decrease amantadine renal clearance and raise plasma levels
Urinary acidifying agents may increase amantadine elimination
Live attenuated influenza vaccine should not be given during amantadine treatment; inactivated vaccines are acceptable
Alcohol not recommended — may potentiate CNS effects (dizziness, confusion) and orthostatic hypotension
Caution with other CNS-active/sedating drugs due to additive somnolence

Hallucinations (common; more frequent in patients ≥65 years — 31% vs 10% in younger patients on Gocovri)
Dizziness/orthostatic hypotension (up to ~29% with Gocovri)
Dry mouth, peripheral edema, constipation
Falls
Somnolence/daytime sleepiness, including sudden sleep onset episodes
Livedo reticularis (with chronic IR amantadine use)
Impulse control disorders — pathological gambling, hypersexuality, compulsive spending/eating
Corneal edema (rare but requires monitoring and possible discontinuation)
Psychiatric effects including depression and suicidal ideation

Assess for daytime somnolence/sudden sleep episodes at baseline and throughout treatment
Screen for depression and suicidal ideation, particularly early in therapy
Monitor for new or worsening hallucinations, especially after dose increases and in elderly patients
Monitor orthostatic blood pressure, particularly with dose titration
Baseline and periodic ophthalmologic evaluation if visual changes occur (corneal edema risk)
Screen for impulse control symptoms (gambling, compulsive behaviors) at follow-up visits
Monitor renal function, especially in elderly patients or those with renal impairment
Taper rather than abruptly stop therapy; monitor for withdrawal-related hyperthermia/rigidity

Pregnancy: animal reproduction studies showed potential for fetal harm at clinically relevant exposures; no adequate/well-controlled human data available for either IR amantadine or Gocovri
Lactation: amantadine is excreted into human breast milk; effects on the breastfed infant are not well characterized
Amantadine may reduce prolactin levels and theoretically suppress lactation
Use in pregnancy/lactation only if potential benefit justifies potential risk to fetus/infant