Do your patients accept OFF time to avoid dyskinesia?

Motor complications can develop early and frequently in the general PD population1

More than 50% developed motor complications within 5 years of diagnosis1

Pie charts displaying percentages of patients developing early motor complications of PD.

Of those, more than 1 in 4 experience both motor fluctuations and dyskinesia1

Which motor complication is more bothersome to your patients?

In a 2020 survey of healthcare providers (HCPs) and patients, the majority of HCPs prioritized treating OFF time vs. dyskinesia. However, the majority of patients who experience both prioritized managing dyskinesia.2

As motor complications emerge and levodopa adjustments are made, patients may accept a trade-off between OFF time and dyskinesia.3

Illustration of trade-off between OFF time and dyskinesia with levodopa dose adjustments.

Now, as motor complications emerge, you and your patients don't have to compromise between OFF time and dyskinesia.4

When motor complications occur, it may be beneficial to consider adding an NMDA, N-methyl-D-aspartate, antagonist (glutamatergic pathway) to complement the current dopaminergic treatment regimen.*,5

*The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia and OFF time in patients with PD is unknown.4

Understanding the role of glutamate in PD

Dopamine is only part of the story when it comes to controlling motor complications.5

  • NMDA Receptor
  • Glutamate
  • Dopamine Receptor
  • Dopamine
  • NMDA Antagonist

Reducing glutamate hyperactivity through the NMDA receptor could be critical to reducing dyskinesia and OFF time†,5

NMDA. A synthetic amino acid C5N9NO4 that binds selectively to a subset of glutamate receptors on neurons.14

†The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia and OFF time in patients with PD is unknown.4

How amantadine is believed to work

AMANTADINE IS AN NMDA ANTAGONIST USED IN PD TREATMENT‡,15,16

  • Amantadine is used for symptomatic treatment for PD and can reduce levodopa-induced dyskinesia and OFF time15,18,19
  • The mechanism by which amantadine exerts efficacy in the treatment of dyskinesia and OFF time in patients with PD is unknown4
    • May work by reducing excessive glutamatergic activity, which contributes to dyskinesia and OFF time7
    • Amantadine may have direct and indirect effects on dopamine neurons; it exerts dopaminergic-like side effects such as hallucinations and dizziness in humans15
  • Common daily dosing of amantadine HCl IR in PD is 100 mg BID15
  • NMDA Receptor
  • Glutamate
  • Dopamine Receptor
  • Dopamine
  • NMDA Antagonist
Illustration of the effect of amantadine on glutamate hyperactivity through the NMDA receptor during dyskinesia.

‡Amantadine is a low-affinity, noncompetitive NMDA antagonist, which means inhibition of the NMDA channel occurs at a different binding site than the active site where the substrate binds.15-17

Do you have patients with PD like these?

Dyskinesia and OFF time are affecting their daily lives. See their stories and why you may want to consider GOCOVRI.

Matt's motor complications are affecting his success as a salesperson.

"I have these involuntary neck movements from dyskinesia or freezing from OFF time. They distract me and my clients. When I try to control them, they only seem to get worse."

How can Matt manage motor symptoms starting from young onset PD?

Learn More

Matt is a people person who knows his field inside out. It made him a natural to become a salesperson for his company. This is the job he's been working toward his whole career.

Communicating with clients under pressure—virtually and in-person—is essential to his job.

Matt can never be sure what the day will bring. At one key meeting, his dyskinesia was particularly noticeable; at another, he was experiencing OFF episodes. His confidence is shattered.

Treatment History

  • Initiated with Azilect 1 mg QID, then added Sinemet 25 mg/100 mg TID. Later, he started experiencing OFF episodes and a fourth dose of Sinemet was added daily
  • Matt's OFF episodes have improved a little with an increased Sinemet dose, but his dyskinesia is increasing and he is having more motor complications throughout the day

Currently Taking

  • Azilect 1 mg QID
  • Sinemet 25 mg/100 mg QID

Betty’s motor complications make daily tasks challenging.

"My neurologist told me increasing my dose of Sinemet would make my dyskinesia worse. Is this really the best my treatment can get?"

Must Betty accept OFF episodes to avoid dyskinesia?

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These were the years Betty and her husband had worked so hard for. She hoped to spend retirement gardening and going to her grandkids' games.

Betty had been struggling with OFF episodes, and her doctor increased her levodopa. But now, she's starting to experience dyskinesia—and it’s getting in the way of everything she and her husband want to do.

She feels guilty about not being able to start their next chapter together.

Treatment History

  • Started on Sinemet 25 mg/100 mg TID, then went to QID
  • One year later, added Comtan 200 mg QID for OFF episodes

Currently Taking

  • Sinemet 25 mg/100 mg QID
  • Comtan 200 mg QID–but she is starting to experience dyskinesia

Tom’s motor complications make it difficult for him to get out and socialize.

"I retired from work, not life. But I’m afraid to speak to my doctor about my dyskinesia because I don’t want her to reduce my levodopa dose."

Must Tom accept dyskinesia to avoid OFF episodes?

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Tom is a textbook extrovert—the type of guy who tells great stories and loves seeing friends.

Lately though, Tom and his wife, Jean, have been turning down a lot of invitations.

At a recent gathering with buddies, his dyskinesia caused him to have trouble using utensils, embarrassing him. He’s isolating more and more, which worries his wife.

Treatment History

  • Was initiated on Mirapex ER at diagnosis, but later discontinued due to side effects
  • Tried amantadine IR early on and it worked for tremor
  • Experiences pronounced dyskinesia at various times throughout the day

Currently Taking

  • Rytary 3 capsules 36.25 mg/145 mg TID
  • Amantadine IR 100 mg BID

Joe’s motor complications are getting in the way of teaching.

"My slow reaction times and difficulty getting up and standing in front of the class make it hard for me to teach."

How can Joe better manage his OFF episodes?

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Joe is the type of teacher few students forget. He loves to teach—which is clear from his spirited, animated style.

These days, though, Joe is just trying to get through class himself.

Visibly struggling with slow movement and tremor by the end of the period, Joe feels more like a distraction than an educator. Embarrassed, he now mostly lectures from his desk.

Treatment History

  • Started on Sinemet 25 mg/100 mg TID
  • After 1 year, his tremor and slowness were not as well controlled, and his dose was increased to 25 mg/100 mg QID

Currently Taking

  • Sinemet 25 mg/100 mg QID

What efficacy data does GOCOVRI have?

GOCOVRI is backed by 2 Phase 3 clinical trials. These studies assessed the ability of GOCOVRI to reduce dyskinesia (primary endpoint), reduce OFF time (secondary endpoint), and increase GOOD ON time (secondary endpoint).4,19,20

See Efficacy Data

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Important Safety Information

IMPORTANT SAFETY INFORMATION AND INDICATION

CONTRAINDICATIONS

GOCOVRI 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.

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
  • As adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes

It is not known if GOCOVRI is safe and effective in children.

Please see full Prescribing Information and Patient Information.

Abbreviations: BID, 2 times a day; IR, immediate release; OLE, open-label extension; PD, Parkinson's disease; QID, 4 times a day; TID, 3 times a day.

References: 1. Bjornestad A, Forsaa EB, Pedersen KF, et al. Risk and course of motor complications in a population-based incident Parkinson's disease cohort. Parkinsonism Relat Disord. 2016;22:48-53. doi:10.1016/j.parkreldis.2015.11.007 2. Data on file. Adamas Pharma LL. 3. Jankovic J, Stacy M. Medical management of levodopa-associated motor complications in patients with Parkinson's disease. CNS Drugs. 2007;21(8):677-692. doi:10.2165/00023210-200721080-00005 4. GOCOVRI® (amantadine). Prescribing Information. Adamas Pharma LLC. 5. Encarnacion EV, Hauser RA. Levodopa-induced dyskinesias in Parkinson's disease: etiology, impact on quality of life, and treatments. Eur Neurol. 2008;60(2):57-66. doi:10.1159/000131893. 6. Rajan R, Popa T, Quartarone A, Ghilardi MF, Kishore A. Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease: connecting the dots in a multicomponent network. Clin Neurophysiol. 2017;128(6):992-999. doi:10.1016/j.clinph.2017.03.043 7. 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. doi:10.1007/s40263-012-0016-z 8. Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011;34:441-466. doi:10.1146/annurev-neuro-061010-113641 9. Surmeier DJ, Ding J, Day M, Wang Z, Shen W. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci. 2007;30(5):228-235. doi:10.1016/j.tins.2007.03.008 10. Ahmed I, Bose SK, Pavese N, et al. Glutamate NMDA receptor dysregulation in Parkinson's disease with dyskinesias. Brain. 2011;134(4):979-986. doi:10.1093/brain/awr028 11. Sharma VD, Lyons KE, Pahwa R. Amantadine extended-release capsules for levodopa-induced dyskinesia in patients with Parkinson's disease. Ther Clin Risk Manag. 2018;14:665-673. doi:10.2147/TCRM.S144481 12. Manson A, Stirpe P, Schrag A. Levodopa-induced-dyskinesias clinical features, incidence, risk factors, management and impact on quality of life. J Parkinsons Dis. 2012;2(3):189-198. doi:10.3233/JPD-2012-120103 13. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson's disease (2009). Neurology. 2009;72(21 Suppl 4):S1-136. doi:10.1212/WNL.0b013e3181a1d44c 14. National Library of Medicine, PubChem. NIH. N-methyl-D-aspartic acid. https://pubchem.ncbi.nlm.nih.gov/compound/22880. Accessed June 16, 2022. 15. Symmetrel® (amantadine hydrochloride, USP). Prescribing Information. Endo Pharmaceuticals Inc. 16. Parsons CG, Quack G, Bresink I, et al. Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo. Neuropharmacology. 1995;34(10):1239-1258. doi:10.1016/0028-3908(95)00092-k 17. Blanpied TA, Clarke RJ, Johnson JW. Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J Neurosci. 2005;25(13):3312-3322. doi:10.1523/JNEUROSCI.4262-04.2005 18. Crosby N, Deane KH, Clarke CE. Amantadine in Parkinson's disease. Cochrane Database Syst Rev. 2003;(1):CD003468. doi:10.1002/14651858.CD003468 19. Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson's disease. CNS Drugs. 2018;32(4):387-398. doi:10.1007/s40263-018-0498-4 20. Tanner CM, Pahwa R, Hauser RA, et al. EASE LID 2: a 2-year open-label trial of Gocovri (amantadine) extended release for dyskinesia in Parkinson's disease. J Parkinsons Dis. 2020;10(2):543-558. doi:10.3233/JPD-191841

Important Safety Information

IMPORTANT SAFETY INFORMATION AND INDICATION

CONTRAINDICATIONS

GOCOVRI 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.

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
  • As adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes

It is not known if GOCOVRI is safe and effective in children.

Please see full Prescribing Information and Patient Information.