Drugs For Parkinson's Disease: Pharmacist'S Letter / Prescriber'S Letter

PL Detail-Document #310708
This PL Detail-Document gives subscribers

additional insight related to the Recommendations published in
PHARMACISTS LETTER / PRESCRIBERS LETTER

July 2015
Drugs for Parkinsons Disease

Parkinsons disease is a neurologic disease characterized by tremor, rigidity, and bradykinesia.1,2 Initial treatments often include low doses of
carbidopa/levodopa or a dopamine agonist.1 But eventually the drugs dont work as well in many patients because Parkinsons is a progressive
disease. Suboptimal control can be managed by increasing the dose of the dopamine agonist or levodopa. But this approach increases the chance of
dopamine agonist side effects (e.g., neuropsychiatric side effects, sedation, sleep attacks).5 It can also cause or worsen dopamine-associated
dyskinesias.5,6 So most clinicians prefer to use a combination of agents rather than increase the dose of a single agent after the initial honeymoon.5
This period of good control lasts about five years with levodopa, after which motor fluctuations (e.g., wearing off, on-off phenomenon) and
dyskinesias develop.5,6 The chart below outlines the place in therapy of common medications used to treat motor symptoms of Parkinsons disease.
Tips for managing motor symptoms in more advanced Parkinsons disease and other therapeutic pearls are also included.
Drug or Drug Class
Role in Therapy
Comments
Levodopa-carbidopa
(Sinemet, Sinemet CR,
Rytary [U.S.], Parcopa
[U.S.; generics only,
brand not available],
Duopa [U.S.])
Most effective drug for

Parkinsons symptoms.1
Can be used first-line,
especially in older
patients (e.g., over 70
years).1,7
Long-term use associated with dyskinesias and motor fluctuations (on-off, wearing off).1,5
Other side effects include nausea (take with food), loss of appetite, orthostasis (use lowest
dose necessary, stop alpha antagonists), confusion (reduce or stop anticholinergics or
sedating meds), hallucinations (reduce dose), constipation, dry mouth, headache.5,7
Either an immediate- or controlled-release product can be used for initial therapy.1 Oral
disintegrating tablets (U.S. only) are an option for patients with difficulty swallowing.
For suboptimal therapeutic response, consider dose increase (not preferred) or addition of
dopamine agonist, but watch for dyskinesias and other side effects.5,9
For peak dose dyskinesias, consider dose reduction +/- dopamine agonist, or add
amantadine.2,5,6
Controlled-release levodopa-carbidopa does not reduce off time better than immediaterelease.2 However, Rytary (U.S.), which has a quicker onset than controlled-release and a
longer duration than immediate-release, does reduce off time by about 70 min/day
compared to immediate-release.16 Only preliminary evidence is available comparing
Rytary with controlled-release levodopa-carbidopa.17
Rytary costs ~$700/month compared to $200/month for generic products.
To reduce off time, consider addition of MAO-B inhibitor, dopamine agonist, or COMT
inhibitor.2,9 May require levodopa-carbidopa dose reduction.2
Wearing off might also be reduced by shortening the levodopa dosing interval by 30 to 60
minutes.13 Add an extra dose at the end of the day if needed.13
Levodopa-benserazide
(Prolopa [Canada])
Levodopa-carbidopaentacapone (Stalevo)
Note: Rytary dosing is
not interchangeable with
immediate- or sustainedrelease carbidopalevodopa products.
Dosing conversion
information can be found
in the product labeling
for Rytary at
www.rytary.com
More. . .
Copyright 2015 by Therapeutic Research Center
3120 W. March Lane, Stockton, CA 95219 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.PharmacistsLetter.com ~ www.PrescribersLetter.com ~ www.PharmacyTechniciansLetter.com
(PL Detail-Document #310708: Page 2 of 4)
Drug or Drug Class
Role in Therapy
Comments
Dopamine agonist
(pramipexole [Mirapex,
generics, Mirapex ER
(U.S.)], ropinirole
[Requip, generics,
Requip XL (U.S.)],
rotigotine [Neupro])
Not as effective as
levodopa-carbidopa for
Parkinsons symptoms.1
Can be used first-line,
especially in younger
patients (less than 50
years).1,7
Can be added to
levodopa to reduce off
time, improve
symptoms, or manage
dyskinesias due to
levodopa-carbidopa.2,5,6
Mild to moderate
benefit.1,4
Can be used first-line.1
Can be added to
time.2
May have antidepressant
effects.1
Insufficient evidence of
neuroprotection.3
More expensive than levodopa-carbidopa.1

Side effects similar to levodopa-carbidopa (see below).10
Lower risk of dyskinesias, wearing off, and on-off fluctuations than levodopa-carbidopa.1
Higher risk of hallucinations, sleepiness, and edema than levodopa-carbidopa.1
May impair impulse control (e.g., gambling, shopping). Warn patient. Management
includes dose reduction or discontinuation. Consider referral.10
May cause excessive sleepiness sleep attack. Caution patient about driving. May
require stimulant or switch to levodopa.10
In event of confusion, consider switch to levodopa or reduce/stop anticholinergic or
sedating medications.10
Adjunct to levodopacarbidopa; not for

monotherapy.9
Can be added to
time.9
Prolongs the duration of action of levodopa.9

Combo product with levodopa-carbidopa plus entacapone (Stalevo) available. Decreases
pill burden and may cost less than separate Rxs for Comtan plus carbidopa/levodopa.
Addition of COMT inhibitor can increase levodopa-carbidopa side effects, including
dyskinesias. Levodopa dose may need to be decreased.9
Entacapone can cause orange urine.9
Tolcapone requires liver function test monitoring.9
COMT inhibitors also cause gastrointestinal side effects.9
Monoamine oxidase
type B (MAO-B)
inhibitors (selegiline,
generics, Eldepryl
[U.S.], Zelapar [U.S.],
rasagiline [Azilect])
Catechol-O-methyl
transferase (COMT)
inhibitor
(entacapone [Comtan],
tolcapone [U.S.;
Tasmar])
Rasagiline better studied for reducing off time, but no proof it works better than
selegiline.2
Note that transdermal selegiline (Emsam) is used for depression only, not Parkinsons
disease.3 It has not been studied for Parkinsons and it achieves higher plasma levels than
oral.15
May cause orthostasis or hallucinations, especially with levodopa.3,4
Other side effects include: nausea, dry mouth, constipation, lightheadedness, agitation,
insomnia, vivid dreams (give selegiline morning/noon to reduce effects on sleep).11
May worsen dyskinesias when used with levodopa.4
Many potential drug interactions due to MAO inhibition (e.g., antidepressants [commonly
combined, however], tramadol, meperidine, methadone, dextromethorphan).3,11 Watch for
flushing, hypertension, and agitation if given with antidepressants.11
More. . .
Drug or Drug Class
Role in Therapy
Comments
Amantadine
Mild to modest
immediate benefit for
most symptoms.1,8
Can be used first-line or
be added to levodopa for
dyskinesias or
tremor.1,2,8
Efficacy may wane after weeks or months.8

Side effects include: cognitive impairment, confusion, insomnia, hallucinations, livedo
reticularis (cosmetic problem only).5,6,8
Well-tolerated in younger patients.1,5
Requires renal dose adjustment.5
Anticholinergics
(trihexyphenidyl,
benztropine)
Initial monotherapy or
adjunct, especially if
tremor is main symptom
and patient is young.1,12
Risk of cognitive impairment and confusion; use with caution in patients over 60 years of
age.5,12
Other side effects include: dry mouth, urinary retention, constipation, drowsiness.12
Apomorphine
(Apokyn, generics
[U.S.])
To reduce off time in

advanced disease.2
Subcutaneous injection.14
Short duration of action.14
Must administer with an antiemetic to prevent nausea/vomiting, but not a 5-HT3
antagonist (e.g., ondansetron) due to risk of profound hypotension.14
Other labeled warnings: hypotension, syncope, QT prolongation, cardiac events,
hallucinations, psychosis, excessive sleepiness, priapism.14
Other side effects: yawning, dyskinesias, dizziness, runny nose, edema, sweating,
flushing, pallor.14
Reduce dose in renal impairment.14
Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making
clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national
organizations. Information and internet links in this article were current as of the date of publication.
More. . .
Project Leaders in preparation of this PL DetailDocument:

Melanie Cupp, Pharm.D., BCPS
(Original September 2011); Stacy A. Hester, R.Ph.,
BCPS, Assistant Editor (July 2015 update)
8.
9.
References
1.
2.
3.
4.
5.
6.
7.
Miyasaki JM, Martin W, Suchowersky O, et al.

Practice parameter: initiation of treatment for
Parkinsons disease: an evidence-based review:
report of the Quality Standards Subcommittee of the
American Academy of Neurology. Neurology
2002;58:11-7.
Pahwa R, Factor SA, Lyons KE, et al. Practice
parameter: treatment of Parkinson disease with
motor fluctuations and dyskinesia (an evidencebased review): report of the Quality Standards
Subcommittee of the American Academy of
Neurology. Neurology 2006;66:983-95.
PL Detail-Document, New treatments for Parkinson's
disease (Azilect and Zelapar). Pharmacist's
Letter/Prescribers Letter. July 2006.
Robottom BJ.
Efficacy, safety, and patient
preference of monoamine oxidase B inhibitors in the
treatment of Parkinsons disease. Patient Prefer
Adherence 2011;5:57-64.
Olanow CW, Watts RL, Koller WC. An algorithm
(decision tree) for the management of Parkinsons
disease (2001): treatment guidelines. Neurology
2001;56(11 Suppl 5):S1-88.
Aviles-Olmos I, Martinez-Fernandez R, Foltynie T.
L-dopa-induced dyskinesias in Parkinsons disease.
Eur Neurol J 2010;2:91-100.
National Parkinson Foundation. Parkinsons Toolkit.
Levodopa.
http://www.toolkit.parkinson.org/content/levodopa.
(Accessed June 5, 2015).
10.
11.
12.
13.
14.
15.
16.
17.
National Parkinson Foundation. Parkinsons Toolkit

Other
medications.
http://www.toolkit.parkinson.org/content/othermedications. (Accessed June 5, 2015).
National Parkinson Foundation. Parkinsons Toolkit
COMT
inhibitors.
http://www.toolkit.parkinson.org/content/comtinhibitors. (Accessed June 5, 2015).
Dopamine
agonists.
http://www.toolkit.parkinson.org/content/dopamineagonists. (Accessed June 5, 2015).
MAO-B
inhibitors.
http://www.toolkit.parkinson.org/content/mao-binhibitors. (Accessed June 5, 2015).
Anti-cholinergics.
http://www.toolkit.parkinson.org/content/anticholinergics. (Accessed June 5, 2015).
Tarsy D.
Motor fluctuations and dyskinesia in
Parkinson disease. November 3, 2014. UpToDate.
Product information for Apokyn. The Ipsen Group.
Brisbane, CA 94005. July 2014.
PL
Detail-Document,
Emsam
(Selegiline)
Transdermal Patch. Pharmacists Letter/Prescribers
Letter. April 2006.
Product information for Rytary. Impax. Hayward, CA
94544. January 2015.
Tetrud J, Liang G, Ellenbogen A, et al. Motor
function assessment in advanced Parkinsons
disease (PD) after IPX066 and controlled-release
carbidopa-levodopa (CR) using the Unified
Parkinsons Disease Rating Scale (UPDRS) and the
objective Parkinsons disease measurement (OPDM)
[Abstract]. Mov Disord 2014;29(Suppl 1):S270.
Cite this document as follows:

PL Detail-Document, Drugs for Parkinsons Disease.
Letter/Prescribers Letter. July 2015.
Evidence and Recommendations You Can Trust

3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249
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PL Detail-Document #310708

This PL Detail-Document gives subscribers

PHARMACISTS LETTER / PRESCRIBERS LETTER

Drugs for Parkinsons Disease

Drug or Drug Class

Most effective drug for

(PL Detail-Document #310708: Page 2 of 4)

Drug or Drug Class

More expensive than levodopa-carbidopa.1

Adjunct to levodopacarbidopa; not for

Prolongs the duration of action of levodopa.9

(PL Detail-Document #310708: Page 3 of 4)

Drug or Drug Class

Efficacy may wane after weeks or months.8

To reduce off time in

(PL Detail-Document #310708: Page 4 of 4)

Project Leaders in preparation of this PL DetailDocument:

Miyasaki JM, Martin W, Suchowersky O, et al.

National Parkinson Foundation. Parkinsons Toolkit

Cite this document as follows:

Evidence and Recommendations You Can Trust

Subscribers to the Letter can get PL Detail-Documents, like this one,

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