Class or specific agent		Role in therapy	Dosage forms available	Dosing pearls	Adverse effects	Advantages	Disadvantages	Cost* for 30-day supply
Amantadine (Gocovri, Osmolex ER)		Treatment of dyskinesias associated with carbidopa/levodopa (Sinemet, Rytary) therapy	Amantadine: 100-mg immediate-release tablets Gocovri: 68.5-mg and 137-mg extended-release capsules Osmolex ER: 129-mg, 193-mg, and 258-mg tablets	Immediate release: 100 mg 1 to 2 times per day (maximum dosage: 400 mg per day) Extended release: start with lowest dose 1 time per day and titrate up weekly based on symptoms Do not discontinue abruptly; taper over several weeks	Orthostasis, peripheral edema, hallucinations, delusions, paranoia, dizziness, livedo reticularis, abnormal dreams, altered cognition, insomnia, confusion, drowsiness, agitation, depression, suicidal ideation, anxiety	Most helpful for dyskinesias; add to levodopa therapy	Not ideal for older adults secondary to cognitive effects and psychosis	Amantadine: $20 Gocovri: NA Osmolex ER: $500
Anticholinergics
	Benztropine  Trihexyphenidyl	Early treatment of motor symptoms, primarily tremor	Benztropine: 0.5-mg, 1-mg, and 2-mg tablets Trihexyphenidyl: 2-mg and 5-mg tablets	Benztropine: 0.5 mg 1 time per day at bedtime; titrate up by 0.5 mg weekly based on response and tolerability (maximum dosage: 6 mg per day) Administer in 2 to 4 divided doses with higher dosing Trihexyphenidyl: 1 mg per day; titrate up by 2-mg increments weekly based on symptoms (maximum dosage: 15 mg per day) Administer in 3 to 4 divided doses with higher dosing	Constipation, urinary retention, dry eyes, dry mouth, altered cognition, altered prolactin levels	Effective for managing tremors that are the predominant motor symptom	Not effective for bradykinesias or dyskinesias Adverse effect profile not well tolerated by older adults	Benztropine: $10 Trihexyphenidyl: $10
Dopamine agonists
	Nonergot: pramipexole (Mirapex), ropinirole (Requip XL), rotigotine (Neupro)	Early treatment of motor symptoms that are not too disruptive and an additive to carbidopa/levodopa therapy to minimize effects of off periods	Pramipexole and Mirapex: 0.125-mg, 0.25-mg, 0.5-mg, 0.75-mg, 1-mg, and 1.5-mg immediate-release tablets Pramipexole ER and Mirapex ER: 0.375-mg, 0.75-mg, 1.5-mg, 2.25-mg, 3-mg, 3.75-mg, and 4.5-mg tablets Ropinirole: 0.25-mg, 0.5-mg, 1-mg, 2-mg, 3-mg, 4-mg, and 5-mg immediate-release tablets Ropinirole ER and Requip XL: 2-mg, 4-mg, 6-mg, 8-mg, and 12-mg tablets Neupro: 1-mg, 2-mg, 3-mg, 4-mg, 6-mg, and 8-mg transdermal patches	Pramipexole and ropinirole: start with lowest dose 3 times per day Pramipexole ER and ropinirole ER: start with lowest dose 1 time per day May titrate up every 5 to 7 days as needed for symptom management Rotigotine transdermal patch: start with lowest dose applied 1 time per day May titrate up every 5 to 7 days Do not discontinue abruptly; taper over several weeks	Impulse control disorder, psychosis, hallucinations, delusions, dyskinesias, lower extremity edema, constipation, nausea, somnolence, sleep attacks, insomnia, dizziness, orthostasis, hypotension, melanoma Pramipexole: heart failure exacerbation	Good initial option to treat motor symptoms but not as effective as levodopa therapy Lower risk of motor complications with prolonged use compared with levodopa therapy	High risk of impulse control disorder May require decrease in dose or stopping completely to manage impulse control disorder Inquire about sleep attacks and excessive daytime somnolence Has potential to exacerbate dyskinesias Monitor for melanoma on regular basis	Pramipexole: $10 Mirapex: $220 Pramipexole ER: $80 Mirapex ER: $650 Ropinirole: $20 Ropinirole ER: $20 Requip XL: $25 Neupro: $700
	Apomorphine (Apokyn)	Apomorphine for severe freezing episodes	Apokyn subcutaneous injection: 30 mg per 3 mL	Apomorphine: start with lowest dose possible and may titrate as needed every few days to effect; pen is marked in mL, not mg, which makes it prone to dosing errors; must have first dose administered in office; antiemetic should be administered 3 days before test dose	Hypersensitivity reaction, severe hypotension, severe nausea, vomiting (premedicate with antiemetic trimethobenzamide [Tigan] before use), pulmonary fibrosis, somnolence, dyskinesias, QTc prolongation, confusion, altered cognitive function	Works quickly to resolve freezing episodes	Initial test doses should be administered in the office and observed for at least 1 hour and up to 2 hours for response to off periods and safety (hypotension) Most patients will not take long-term because of the adverse effect profile	Apokyn: NA; only available through specialty pharmacies
Catechol O-methyltransferase inhibitors
	Entacapone (Comtan)  Tolcapone (Tasmar)  Opicapone (Ongentys)	Additive to carbidopa/levodopa therapy to minimize effects of off periods; do not administer as monotherapy	Entacapone and Comtan: 200-mg tablets Also available as combination carbidopa/entacapone/levodopa (Stalevo): 12.5-mg/50-mg/200-mg, 18.75-mg/75-mg/200-mg, 25-mg/100-mg/200-mg, 31.25-mg/125-mg/200-mg, 37.5-mg/150-mg/200-mg, 50-mg/200-mg/200-mg tablets Tolcapone: 100-mg tablets Opicapone: 50-mg tablets; FDA approved in April 2020 but NA in U.S. market	Entacapone: 200 mg with each dose of carbidopa/levodopa up to 8 times per day (maximum dosage: 1,600 mg per day) Opicapone: 50 mg once nightly; dosage decrease with moderate hepatic dysfunction to 25 mg 1 time per day	Orthostatic hypotension, potential to worsen dyskinesias when added to levodopa therapy, urine discoloration (e.g., dark orange or brown), constipation, fatigue	Increases effectiveness (reduces off effects) of carbidopa/levodopa therapy	Tolcapone associated with fulminant hepatic failure; use should be limited	Entacapone: $35 Comtan: $660 Tolcapone: $1,425 Tasmar: $11,150† Carbidopa/levodopa/entacapone: $55 Stalevo: $100 Opicapone: NA in U.S. market
Adenosine A2A antagonists
	Istradefylline (Nourianz)	Additive to carbidopa/levodopa therapy to minimize effects of off periods; do not administer as monotherapy	Nourianz: 20-mg and 40-mg	Start with 20 mg 1 time per day; may increase to 40 mg based on response and tolerability	Dyskinesias when added to carbidopa/levodopa therapy, dizziness, constipation, nausea, hallucinations, insomnia, impulse control disorder, psychosis	Increases effectiveness (reduces off effects) of carbidopa/levodopa therapy	Cost because it will only be available as brand-name medication	Nourianz: $1,500
	Carbidopa/levodopa (Sinemet; Rytary; Inbrija; Duopa)	First choice for management of motor symptoms	Carbidopa/levodopa and Sinemet: 10-mg/100-mg, 25-mg/100-mg, and 25-mg/250-mg immediate-release and orally disintegrating tablets Carbidopa/levodopa ER: 25-mg/100-mg and 50-mg/200-mg tablets Rytary immediate and extended release combined: 23.75-mg/95-mg, 36.25-mg/145-mg, 48.75-mg/195-mg, 61.25-mg/245-mg capsules Inbrija: 42 mg powder for inhalation Duopa: 4.63-mg/20-mg per mL enteral suspension	Carbidopa/levodopa is most effective on an empty stomach Start with lowest immediate-release dose 3 times per day Once a patient is taking 3 of the 25-mg/100-mg tablets 3 times per day, increasing the dose further adds no additional benefit and more frequent dosing intervals should be considered May require dosing over time with a higher dose 4 to 5 times per day Controlled-release dose converted from immediate-release dosing equivalents administered 2 times per day; controlled release has sporadic absorption in some patients Rytary: start with lowest dose 3 times per day; may require higher, more frequent dosing (4 to 5 times per day) over time Inbrija: 84 mg as needed for off periods up to 5 times per day Duopa: dose to be administered based on conversion of immediate-release dosing (maximum dosage: 2,000 mg per day) administered over 16 hours; nighttime symptoms are managed with immediate-release levodopa Dose and frequency adjustments are required to manage dyskinesias and off periods over time Do not withhold therapy for long periods, even if the patient is directed to take nothing by mouth, because it could result in akathisia and neuroleptic malignant syndrome Do not discontinue abruptly; taper over several weeks	Hallucinations, delusions, dyskinesias, lower extremity edema, nausea, somnolence, dizziness, orthostasis, depression, suicidal ideation Inbrija: cough, upper respiratory infection Duopa: site complications, abdominal pain, infections	Immediate-release formulation is first choice for treatment of motor symptoms Rytary may improve a patient's on time (when medication is effectively controlling symptoms), but dyskinesias similar to immediate release Inbrija may help with freezing and off periods that are unpredictable Duopa may improve on time and severe dyskinesias	High risk of developing motor complications from use Prone to off periods as disease progresses, which may present as anxiety, akathisia, apathy, depression, bradykinesias, and freezing	Carbidopa/levodopa: $9 Carbidopa/levodopa orally disintegrating tablet: $37 Carbidopa/levodopa ER: $30 Rytary: $352 Inbrija: NA Duopa: NA
Monoamine oxidase-B inhibitors
	Rasagiline (Azilect)  Selegiline (Zelapar)  Safinamide (generic not currently available in United States; Xadago)	Early treatment of motor symptoms that are not too disruptive (rasagiline and selegiline only) and an additive to carbidopa/levodopa therapy to minimize effects of off periods (all)	Rasagiline and Azilect: 0.5-mg and 1-mg tablets Selegiline: 5-mg tablets and capsules Zelapar: 1.25-mg orally disintegrating tablet Xadago: 50-mg and 100-mg tablets	Rasagiline: 1 mg 1 time per day Selegiline: 5 mg 2 times per day (maximum dosage: 10 mg per day) Xadago: 50 mg 1 time per day; may increase in 2 weeks to maximum dosage of 100-mg 1 time per day based on symptoms	Nausea, dizziness, hallucinations, dry mouth, vivid dreams, headaches, dyskinesias when used with a dopamine agonist or carbidopa/levodopa therapy Rasagiline: increased risk of melanoma	Improves on time when added to levodopa therapy Generally well tolerated	Not as effective as carbidopa/levodopa therapy for motor symptoms Limited risk of serotonin syndrome with other serotonergic medications but is not risk-free	Rasagiline: $70 Azilect: $825 Selegiline: $40 Zelapar: $2,250 Xadago: $825