Medication Management and Strategies for Wearing Off ... • Side effects

©2015 Davis Phinney Foundation

The Victory Summit®– San Antonio, TX | November 14, 2015 www.DavisPhinneyFoundation.org

“When the levodopa honeymoon is over”

Eric J Pappert, MDParkinson’s Disease & Movement Disorders Center

Neurology Associates

“When the levodopa honeymoon is over”

Eric J Pappert, MDParkinson’s Disease & Movement Disorders Center

Neurology Associates

Medication Management& Strategies

Medication Management& Strategies



Medication Options in Parkinson’sMedication Options in Parkinson’s• Carbidopa/Levodopa• Dopamine agonists• COMT-inhibitors• MAO-B Inhibitors• Antiviral agents (amantadine)• Anticholinergic medications

• Carbidopa/Levodopa• Dopamine agonists• COMT-inhibitors• MAO-B Inhibitors• Antiviral agents (amantadine)• Anticholinergic medications



Carbidopa/LevodopaCarbidopa/LevodopaTreats symptoms of: • Stiffness / rigidity• Tremor• Slowness of movement• Walking problems

– Carbidopa reduces nausea and vomitingExamples: Sinemet®, Sinemet CR®, Rytary®, Duopa™, Parcopa®

Treats symptoms of: • Stiffness / rigidity• Tremor• Slowness of movement• Walking problems

– Carbidopa reduces nausea and vomitingExamples: Sinemet®, Sinemet CR®, Rytary®, Duopa™, Parcopa®



Carbidopa/LevodopaCarbidopa/LevodopaAdvantages: • Most effective agent in treating symptoms• Robust response • Long history of use• Relatively rapid absorption• Well tolerated in many people

Advantages: • Most effective agent in treating symptoms• Robust response • Long history of use• Relatively rapid absorption• Well tolerated in many people



Carbidopa/LevodopaCarbidopa/LevodopaLimitations:• Short half-life

– Pulsatile stimulation of dopamine receptors• Does not treat all features of PD

– Freezing, postural instability, autonomic dysfunction, speech abnormalities, dementia

– Eventual diminished response

Limitations:• Short half-life

– Pulsatile stimulation of dopamine receptors• Does not treat all features of PD

– Freezing, postural instability, autonomic dysfunction, speech abnormalities, dementia

– Eventual diminished response



Carbidopa/LevodopaCarbidopa/LevodopaLimitations:• Reduced conversion as disease progresses

– Does not stop disease progression• Emergence of complications

– Motor fluctuations, dyskinesias (involuntary movements caused by medication)

Limitations:• Reduced conversion as disease progresses

– Does not stop disease progression• Emergence of complications

– Motor fluctuations, dyskinesias (involuntary movements caused by medication)



Predictable: Wearing “Off” – Return of Parkinsonian signs or symptoms– Cramping / spasm – “Off Dystonia”– “Sensory / Behavioral / Autonomic Off”

§ Pain, restlessness§ Depression, anxiety, panic attacks§ Sweating, bloating, trouble breathing

Predictable: Wearing “Off” – Return of Parkinsonian signs or symptoms– Cramping / spasm – “Off Dystonia”– “Sensory / Behavioral / Autonomic Off”

§ Pain, restlessness§ Depression, anxiety, panic attacks§ Sweating, bloating, trouble breathing

Motor FluctuationsMotor Fluctuations



Response to Levodopa and Disease Progression – “On/Off”Response to Levodopa and Disease Progression – “On/Off”

EarlyEarly Moderate Moderate AdvancedAdvanced

Clinical Effect

0 2 4 6Time (h)

Olanow CW, Agid Y. Available at: http://www.medscape.com/viewprogram/1847

• Very short duration of motor “ON” response

• “ON” time consistently associated with dyskinesias

• Very short duration of motor “ON” response

• “ON” time consistently associated with dyskinesias

• Shorter duration of motor “ON” response

• Increased incidence of dyskinesias

• Shorter duration of motor “ON” response

• Increased incidence of dyskinesias

• Long duration ofmotor response

• Low incidence of dyskinesias

• Long duration ofmotor response

• Low incidence of dyskinesias

Clinical Effect

0 2 4 6

Clinical Effect

0 2 4 6



Motor FluctuationsMotor FluctuationsUnpredictable:

– Delayed “On” periods, dose failures – Sudden “Off” periods– “Super Offs”– Weak response at end of day

Unpredictable: – Delayed “On” periods, dose failures – Sudden “Off” periods– “Super Offs”– Weak response at end of day



Strategies for Wearing OffStrategies for Wearing Off• Smaller doses of Levodopa less frequently• Low protein diet• Take Levodopa 90 mins

before meals• Consider change in medications:

– Long-acting Levodopa (Sinemet CR®)– Dopamine agonists or MAO-B inhibitors– Continuous dopamine infusion (Duopa®)

• Smaller doses of Levodopa less frequently• Low protein diet• Take Levodopa 90 mins

before meals• Consider change in medications:

– Long-acting Levodopa (Sinemet CR®)– Dopamine agonists or MAO-B inhibitors– Continuous dopamine infusion (Duopa®)







The Classics: Therapies for Motor Fluctuations

Entacapone/ComtanTolcopone/Tasmar

TrihexyphenidylBenztropine

MAO-B InhibitorsRasagiline/AzilectSelegiline/Eldepryl

Levodopa/Carbidopa

Ropinirole/RequipPramipexole/MirapexRotigotine/NeuproApomorphine/Apokyninjection



Dopamine AgonistsDopamine AgonistsAdvantages:• Mimic the effect of dopamine• Longer-lasting effect than Levodopa• Effective single therapy (early Parkinson’s)• Reduced Levodopa-related motor complicationsExamples: Parlodel®, Requip®, Mirapex®, Neupro®, Apokyn®

Advantages:• Mimic the effect of dopamine• Longer-lasting effect than Levodopa• Effective single therapy (early Parkinson’s)• Reduced Levodopa-related motor complicationsExamples: Parlodel®, Requip®, Mirapex®, Neupro®, Apokyn®



Dopamine AgonistsDopamine AgonistsDisadvantages:• Side effects• Does not completely prevent Levodopa-related motor

complications• Additional dopaminergic therapy needed as disease

progresses• Does not treat all features of PD (freezing, postural

instability, autonomic dysfunction, dementia)

Disadvantages:• Side effects• Does not completely prevent Levodopa-related motor

complications• Additional dopaminergic therapy needed as disease

progresses• Does not treat all features of PD (freezing, postural

instability, autonomic dysfunction, dementia)



COMT InhibitorsCOMT InhibitorsAdvantages• Extends duration of Levodopa effect

– By inhibiting enzyme COMT• Addition to Caribdopa/Levodopa for individuals

experiencing “wearing off” effect– No role as single therapy – used only in combination

with LevodopaExamples: Coman®, Tasmar®, Stalevo®

Advantages• Extends duration of Levodopa effect

– By inhibiting enzyme COMT• Addition to Caribdopa/Levodopa for individuals

experiencing “wearing off” effect– No role as single therapy – used only in combination

with LevodopaExamples: Coman®, Tasmar®, Stalevo®



• Light-headedness• Dry mouth• Confusion• Nightmares• Dyskinesias• Drowsiness

• Light-headedness• Dry mouth• Confusion• Nightmares• Dyskinesias• Drowsiness

Common Side Effects of MedicationsCommon Side Effects of Medications



• Impulse control disorders

• Sleep attacks

• Leg swelling

• Impulse control disorders

• Sleep attacks

• Leg swelling

Less Common Side Effects of MedicationsLess Common Side Effects of Medications



Via ElectrodesVia Electrodes

Connected by a Subcutaneous Wire

Connected by a Subcutaneous Wire

Implantable Pulse Generator: Many Current ConfigurationsImplantable Pulse Generator: Many Current Configurations

Deep Brain Stimulation:Chronic (high-frequency) Electrical StimulationDeep Brain Stimulation:Chronic (high-frequency) Electrical Stimulation



/carbidopa

Levodopa/carbidopa IR & CR(RytaryTM)

Levodopa/carbidopa infusion(Duopa®)

The Newcomers: Therapies for Motor Fluctuations

The Newcomers: Therapies for Motor Fluctuations



Opicapone

#1 Inhaled Apomorphine#2 Apomorphine infusion#3 Sublingual Apomorphine

MAO-B InhibitorsSafinamide

/carbidopa#1 Orafuse™ levodopa/carbidopa#2 Inhaled levodopa/carbidopa#3 Melevodopa- Liquid LD/CD#4 Levodopa/carbidopa infusion

Amantadine ER

The Future: Therapies for Motor Fluctuations

The Future: Therapies for Motor Fluctuations



Adenosine A2A Inhibitors: TozadentGlutamate Antagonists: MavoglurantSerotonergic Agonists: Eltoprazine

Adenosine A2A Inhibitors: TozadentGlutamate Antagonists: MavoglurantSerotonergic Agonists: Eltoprazine

The Future:Treatments for DyskinesiasThe Future:Treatments for Dyskinesias



Medication Action ItemsOr “Tenets To Live By”

Medication Action ItemsOr “Tenets To Live By”



Tenet #1Tenet #1You must properly grieve the loss of part of your health and accept this as part of you

1. Denial2. Anger3. Bargaining4. Depression5. Acceptance

You must properly grieve the loss of part of your health and accept this as part of you

1. Denial2. Anger3. Bargaining4. Depression5. Acceptance



You must accept your portion of responsibilityfor your well-being

– General health & diet– Avoiding harm & vanity: using walker– Exercise your body & mind:

• Physical / speech / occupationaltherapies

• Home exercise program / POPS

You must accept your portion of responsibilityfor your well-being

– General health & diet– Avoiding harm & vanity: using walker– Exercise your body & mind:

• Physical / speech / occupationaltherapies

• Home exercise program / POPS

Tenet #2Tenet #2



Be an effective communicator with MD & team– When do you wake up / sleep / eat meals?– List of your medications & times of day– What has changed & when does it occur?– What can’t you do that you must do or want to do?– Non-motor complaints:

• Memory / anxiety / sadness

Be an effective communicator with MD & team– When do you wake up / sleep / eat meals?– List of your medications & times of day– What has changed & when does it occur?– What can’t you do that you must do or want to do?– Non-motor complaints:

• Memory / anxiety / sadness

Tenet #3Tenet #3



Tenet #4Tenet #4Focus on the positive:

– All that remains good– Have a purpose– Don’t allow PD to be who you are

Focus on the positive:– All that remains good– Have a purpose– Don’t allow PD to be who you are



Questions:Questions:“Can you tell us if there are any new medication treatments

in the pipeline for Parkinson’s?”

“What is dystonia?Is it a disease, or just a symptom?”

“Is there anything I can do to slow downthe progression of the disease?”

“Can you tell us if there are any new medication treatmentsin the pipeline for Parkinson’s?”

“What is dystonia?Is it a disease, or just a symptom?”

“Is there anything I can do to slow downthe progression of the disease?”



Questions:Questions:“I’ve been told that exercise is important.

How truly important is exercise to a personwith Parkinson’s?”

“Is it true that taking Levodopa earlier in PD decreases the medication’s long term usefulness?

Does this apply to higher doses also?”

“I’ve been told that exercise is important. How truly important is exercise to a person

with Parkinson’s?”

“Is it true that taking Levodopa earlier in PD decreases the medication’s long term usefulness?

Does this apply to higher doses also?”



Questions:Questions:

“I can’t move at all sometimes. What is the cause, and what should I do about it?

“Do all people with Parkinson’s eventually have dementia? How severe will my cognitive problems become?

“I can’t move at all sometimes. What is the cause, and what should I do about it?

“Do all people with Parkinson’s eventually have dementia? How severe will my cognitive problems become?



Questions:Questions:

Additional questions…Additional questions…



Thank You…Thank You…

Eric J. Pappert, MDParkinson’s Disease & Movement Disorders Center,

Neurology AssociatesSan Antonio, TX

Eric J. Pappert, MDParkinson’s Disease & Movement Disorders Center,

Neurology AssociatesSan Antonio, TX

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Medication Management and Strategies for Wearing Off ... • Side effects