Amantadine

GOCOVRI ® is indicated: For the treatment of dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications As adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes GOCOVRI ® is indicated: For the treatment of dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. As adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes

The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia in patients with Parkinson's disease or as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes is unknown. Amantadine is a weak uncompetitive antagonist of the NMDA receptor. Amantadine has not been shown to possess direct anticholinergic activity in animal studies, however, it exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation in humans. Amantadine may have direct and indirect effects on dopamine neurons, it exerts dopaminergic-like side effects such as hallucinations and dizziness in humans.

Administer orally once daily at bedtime. The initial daily dosage is 137 mg, after 1 week, increase to the recommended daily dosage of 274 mg. Swallow whole, may sprinkle contents on soft food. May be taken with or without food, avoid use with alcohol. A lower dosage is recommended for patients with moderate or severe renal impairment

GOCOVRI is contraindicated in patients with end-stage renal disease (i.e., creatinine clearance below 15 mL/min/1.73 m 2 ). GOCOVRI is contraindicated in patients with end-stage renal disease

Falling Asleep During Activities of Daily Living: Advise patients prior to treatment, ordinarily discontinue if occurs. Suicidality and Depression: Monitor patients for depressed mood, depression, or suicidal ideation or behavior. Hallucinations/Psychotic Behavior: Patients with major psychotic disorder should ordinarily not be treated with GOCOVRI, observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases. Dizziness and Orthostatic Hypotension: Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose. Withdrawal-Emergent Hyperpyrexia and Confusion: Avoid sudden discontinuation. Corneal Edema: Monitor patients for new changes in vision, including blurred vision, with or without eye pain, or vision loss. Taper and discontinue if corneal edema occurs.

The following serious adverse reactions are described in more detail elsewhere in the labeling: Falling Asleep During Activities of Daily Living and Somnolence Suicidality and Depression Hallucinations/Psychotic Behavior Dizziness and Orthostatic Hypotension Withdrawal-Emergent Hyperpyrexia and Confusion Corneal Edema Impulse Control/Compulsive Behaviors The most commonly observed adverse reactions occurring at a frequency of >10% and greater than placebo were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension or http://www.fda.gov/medwatch. 6.1. Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Other Anticholinergic Drugs: Doses should be reduced if atropine-like effects occur. Drugs Affecting Urinary pH: Excretion increases with acidic urine, possible accumulation with urine change towards alkaline. Live Attenuated Influenza Vaccines: Not recommended during use. Alcohol: Concomitant use not recommended

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).