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GOCOVRI blocks NMDA-glutamate receptors to reduce the INTENSITY AND DURATION OF motor complications1

Icons for GOCOVRI, Glutamate,  Calcium,  Dopamine,  and NMDA receptors
Healthy neuronal signaling in motor movement control

Healthy Brain/Early PD2

In healthy brains and early PD, dopaminergic signaling and glutamatergic signaling work together to control movements3


Increased glutamate and upregulated NMDA receptors in progressive PD motor complications

Progressive PD with Motor Complications

As dopaminergic neurons die, fluctuations in dopamine in the striatum dysregulate glutamatergic signaling, leading to increased glutamate and upregulated NMDA receptors. Dyskinesia becomes more likely in the presence of high dopamine levels, while OFF becomes more likely in the presence of low levels of dopamine1,2


GOCOVRI (amantadine) extended release capsules mechanism of action

Mechanism of GOCOVRI

GOCOVRI is thought to reduce the intensity and duration of motor complications by selectively inhibiting overactive NMDA-glutamate receptors1

  • The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia in PD patients is unknown. Amantadine is a weak, uncompetitive antagonist of the NMDA receptor.4

Preclinical data suggest that HIGHER PLASMA CONCENTRATIONS OF AMANTADINE MAY INHIBIT OVERACTIVE GLUTAMATERGIC SIGNALING5

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Important Safety Information

Indication

GOCOVRI™ (amantadine) extended release capsules is indicated for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications.

Contraindications

GOCOVRI™ (amantadine) is contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2.

Warnings and Precautions

Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep during activities of daily living. If a patient develops daytime sleepiness during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued or the patient should be advised to avoid potentially dangerous activities.

Suicidality and Depression: Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression.

Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. 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: Rapid dose reduction or abrupt discontinuation of GOCOVRI, may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. Avoid sudden discontinuation of GOCOVRI.

Impulse Control/Compulsive Behaviors: Patients may experience urges (e.g. gambling, sexual, money spending, binge eating) and the inability to control them. It is important for prescribers to ask patients or their caregivers about the development of new or increased urges. Consider dose reduction or stopping medications.

Adverse Reactions

The most common adverse reactions (>10%) were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.

Drug Interactions

Other Anticholinergic Drugs: The dose of GOCOVRI should be reduced if atropine-like effects are observed.

Drugs Affecting Urinary pH: The pH of the urine has been reported to influence the excretion rate of amantadine. Monitor for efficacy or adverse reactions under conditions that alter the urine pH.

Alcohol: Concomitant use with alcohol is not recommended, as it may increase the potential for CNS effects such as dizziness, confusion, lightheadedness, and orthostatic hypotension.

Indication

GOCOVRI™ (amantadine) extended release capsules is indicated for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications.

References: 1. Gasparini F, Di Paolo T, Gomez-Mancilla B. Metabotropic glutamate receptors for Parkinson's disease therapy. Parkinsons Dis. 2013;196028. 2. Duty S. Targeting glutamate receptors to tackle the pathogenesis, clinical symptoms and levodopa-induced dyskinesia associated with Parkinson's disease. CNS Drugs. 2012;26(12):1017-1032. 3. Cenci MA. Glutamatergic pathways as a target for the treatment of dyskinesias in Parkinson’s disease. Biochem Soc Trans. 2014;42(2):600-604. 4. GOCOVRI™ (amantadine) [Prescribing Information]. Emeryville, CA: Adamas Pharma LLC; 2017. 5. Parsons CG, Panckenko VA, Pinchenko VO, et al. Comparative patch-clamp studies with freshly dissociated rat hippocampal and striatal neurons on the NMDA receptor antagonistic effects of amantadine and memantine. Euro J Neurosc. 1996;8(3):446-454.