Parkinson's Toolkit

Notes:

Bromocriptine (Parlodel®) and pergolide (Permax®), it was confirmed that pergolide (Permax®) and cabergoline  (Dostinex®), another ergot-derived DA not approved by the Food and Drug Administration (FDA) for use in PD, can cause heart valve abnormalities in a significant minority of users. The FDA determined that the risk of using pergolide outweighs the benefit and in March 2007, removed it from the U.S. market for use in PD. Bromocriptine, the first of the DAs to become commercially successful, is still available but infrequently used.

Rotigotine (Neupro®), the newest dopamine agonist, was approved by the FDA in 2007 and is formulated for use as a once-daily transdermal (skin) patch that is changed every 24 hours. Most people with PD have been able to tolerate the patch by rotating the sites on their bodies to which they adhere the patch. The patch was reformulated due to a quality assurance FDA recall in 2008 but was reintroduced back to the US market in 2012.

Apomorphine (Apokyn®) has found a particular niche as a self-injectable “rescue” drug for people with advanced PD and severe “off” episodes. Its short half-life (average 40 minutes) and chemical structure make it difficult if not impossible to take by mouth. An anti-nausea medication (usually trimethobenzamide or Tigan®) is required prior to injection in the early phase of treatment but can be discontinued after the first week or two. Apokyn® can be used as many as five times per day as a rescue agent.

Prescription Recommendations

Pramipexole

• Prescribe:  Pramipexole 0.25 mg tid; Pramipexole ER 0.75 mg once daily
• Instruct:  0.25 mg ½ tab tid for one week, then one tab tid for one week, then two tabs tid for one week and evaluate patient benefit and potential side effects
• If further titration is necessary for symptoms then increase to 3 tabs tid for one week
• Switch to Pramipexole 1 mg
• Instruct:  1 tab tid for one week, then 1.5 tab tid
• A typical dose is 0.75-1 mg tid
• You may stop at any dose given degree of motor benefit required or side effects 

Ropinirole

• Prescribe: Ropirinole  0.25 mg tid or Ropinirole XL 0.75 mg once daily and titrate up to a dose of at least 6 mg total/day divided tid and evaluate for patient benefit and side effects
• Increase dose if needed up to a maximum of 24 mg/day either 3 or 4 times a day
• Typical doses are usually 2-4mg tid

Rotigotine

• Prescribe: rotigotine 2 mg patch applied topically every 24 hours
• Increase if needed up to a maximum of 6 mg per day
• Patient may bathe, shower or swim while wearing the patch; however, the water may losen the patient's patch
• If the edges of the patch lift, tell your patient to tape the patch down with banding tape
• If the patch falls off, tell your patient to apply a new patch for the rest of the day and to apply a new patch the next day at his/her regular time
• Important: the patch should not be used during MRI procedures because it may cause a burn to the site where the patch was applied

Apomorphine

• Test dose: 0.2 mL (2 mg) during “off” period; patient will require pre-treatment with trimethobenzamide or domperidone (not available in the US) to avoid potentially severe nausea
• Initial: 0.2 mL (2 mg) subcutaneously during the "off" period, up to 3 times a day, if test dose tolerated and provided good response
• Maintenance: titrate every few days in 0.1 mL (1 mg) increments upwards to a maximum of 0.6 mL (6 mg) per dose
• Maximum single dose is 0.6 mL (6 mg)
• Maximum: do not administer more than 5 times per day, and do not exceed 2 mL (20 mg) per day
• Usually need anti-nausea medication especially when starting therapy
• Apomorphine is best as a rescue drug for sudden "off" or delayed "on" state
• Sinemet crushed in ginger ale can also provide a rescue-like effect, though not as fast as apomorphine

Side Effects

• Similar to those associated with levodopa including nausea, vomiting, orthosthatic hypotension
• Confusion/delirium: Switch to levodopa over dopamine agonists, use minimum dose, reduce or withdraw anticholinergic medications, reduce or stop any medications that are sedating
• Impulse control disorders: You must ask prior to initiation of drugs and warn patients of this complication.  If this occurs, dopamine agonists should be discontinued or as low as possible, consider referral to a movement disorders specialist and/or neuropsychiatrist or psychiatrist with experience in impulse control disorders
• Dyskinesia can be seen with dopamine agonist but less frequently than levodopa therapy
• Rotigotine patch can cause mild local skin irritation under the patch
• Hypersomnia or daytime somnolence: Use levodopa rather than dopamine agonist, reduce medication in evening before bed, ensure that night time sleep is restorative, check for sleep apnea, consider modafinil or methylphenidate. Alert patient of this issue if patient drives

TIP: Over time the dose and interval of this group of medications may need to be changed like sinemet