Treatment 
Considerations

The current treatment paradigm of dose-adjusting daytime dopaminergic therapies to manage OFF or dyskinesia assumes a trade off is necessary1-5

Patient response to dopaminergic therapies can change over the course of time and affect motor complications on a daily basis.1

GOOD ON TIME
OFF TIME
DYSKINESIA

As Parkinson’s disease (PD) progresses, up to 80% of patients experience OFF, dyskinesia, or both after starting levodopa therapy1

  • 82% of patients who experience dyskinesia also have OFF6
  • 40% of patients who experience OFF also have dyskinesia within 4-6 years7

OFF and dyskinesia can have a physical and emotional impact on patients

Physical symptoms can be very restrictive
OFF: bradykinesia, tremor, rigidity, postural instability8
Dyskinesia: chorea, balance issues9,10

Emotional impact can be severe
1 out of 3 patients feel that motor complications make social interactions difficult11
Patients often feel depressed and experience anxiety2,12

Both dyskinesia and OFF episodes have an impact on PWP’s daily lives11

A survey found that patients with PD cope with dyskinesia and OFF time in similar ways.

% of Patients
Patients who said reducing OFF time is most important
[A]
(n = 17)*
Patients who said reducing OFF and dyskinesia are equally important
[B]
(n = 57)
Patients who said reducing dyskinesia is most important
[C]
(n = 51)
Avoid social interactions / stay home more than they would like
47%
61%
75%
Wear clothing with less fasteners / buttons
59%
67%
59%
Keep arms and hands tight to body to minimize visibility of tremors
47%
49%
55%
Eat meals in private
35%
46%
53%
Use non-verbal communication when possible
24%
46%
43%
Self-adjust medications
29%
26%
37%
None of the above
12%
2%
4%
* Caution: Small base (n > 30)
  Base: Patients and caregivers of patients who have experienced dyskinesia and have used coping mechanisms to cope with dyskinesia • Q10. Which of the following do [you/they] typically do to cope with [your/their] dyskinesia?

Dose adjusting dopaminergic therapy can create a trade off between OFF episodes and dyskinesia1,4

Increasing dopaminergic therapy can exacerbate dyskinesia2-4

Reducing dopaminergic therapy can exacerbate OFF2-4

In a survey of 101 Neurologists and Movement Disorder specialists treating Parkinson’s Disease11:
  • 49% agree there is an unmet need to easily manage dyskinesia when increasing dopaminergic therapy to manage OFF
  • 54% agree there is an unmet need for treatments that reduce both OFF and dyskinesia without adjusting dopaminergic therapy

Patient profiles

Which patients are right for GOCOVRI®?

No two PD patients look exactly alike, but they all have at least 1 thing in common: motor symptoms can have a very real impact on their daily lives. OFF episodes and dyskinesia can be limiting to patients and cause them to withdraw from daily activities and socially isolate.

Read below to learn how these 4 patients struggled with OFF episodes and dyskinesia, and why you may want to consider GOCOVRI®.

JOE

Motor fluctuations associated with Parkinson’s were slowing down this dynamic high school science teacher

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BETTY

Motor complications associated with Parkinson’s were forcing this recent retiree to make some trade offs

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TOM

Motor complications associated with Parkinson’s were forcing this socializer to make trade offs

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MATT

Motor complications associated with Parkinson’s were getting in the way of his success as a salesperson

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Not actual patients.

Motor fluctuations associated with Parkinson’s were slowing down this dynamic high school science teacher

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.

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

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

How can Joe better manage his OFF episodes?

Motor complications associated with Parkinson’s were forcing this recent retiree to make some trade offs

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.

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

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

Must Betty accept OFF episodes to avoid dyskinesia?

Motor complications associated with Parkinson’s were forcing this socializer to make trade offs

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.

“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.”

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/145mg/TID

Amantadine IR 100 mg BID

Must Tom accept dyskinesia to avoid OFF episodes?

Motor complications associated with Parkinson’s were getting in the way of his success as a salesperson

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 towards 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.

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

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

How can Matt manage motor symptoms starting from young onset PD?
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INDICATION and important safety information

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.

IMPORTANT SAFETY INFORMATION

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.

View the full Prescribing Information.

References:
  1. Jankovic J, Stacy M. Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS Drugs. 2007;21(8):677-692.
  2. 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.
  3. 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.
  4. Brooks DJ. Optimizing levodopa therapy for Parkinson’s disease with levodopa/carbidopa/entacapone: implications from a clinical and patient perspective. Neuropsychiatr Dis Treat. 2008;4(1):39-47.
  5. Hattori N, Fujimoto K, Kondo T, Murata M, Stacy M. Patient perspectives on Parkinson’s disease therapy in Japan and the United States: results of two patient surveys. Patient Relat Outcome Meas. 2012;3:31-38.
  6. Santos-García D, de Deus Fonticoba T, Suárez Castro E, et al. Non-motor symptom burden is strongly correlated to motor complications in patients with Parkinson’s disease. Eur J Neurol. 2020;27:1210-1223.
  7. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 2001;16(3):448-458.
  8. Chou KL, Stacy M, Simuni T, et al. The spectrum of “off” in Parkinson’s disease: what have we learned over 40 years? Parkinsonism Relat Disord. 2018;51:9-16.
  9. Pilleri M, Antonini A. Therapeutic strategies to prevent and manage dyskinesias in Parkinson’s disease. Expert Opin Drug Saf. 2015;14(2):281-294.
  10. Unified Dyskinesia Rating Scale (UDysRS). International Parkinson and Movement Disorder Society website. https://www.movementdisorders.org/MDS-Files1/PDFs/UDysRS_English_FINAL.pdf. Accessed June 15, 2021.
  11. Data on file. Adamas Pharma LLC, Emeryville, CA.
  12. Montel S, Bonnet AM, Bungener C. Quality of life in relation to mood, coping strategies, and dyskinesia in Parkinson’s disease. J Geriatr Psychiatry Neurol. 2009;22(2):95-102.

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