Medication for Parkinson Disease

1. Medication for Parkinson Disease Kristin S. Meyer, PharmD, CGP, FASCP, CACP Assistant Professor of Pharmacy Practice Drake University College of Pharmacy and Health Sciences PD is the 2nd most common neurodegenerative disease behind Alzheimer�s.PD is the 2nd most common neurodegenerative disease behind Alzheimer�s.

2. Approaching Treatment of PD Mimic dopamine Increase dopamine Decrease acetylcholine The dopamine/acetylcholine �see-saw�

3. Anticholinergic Medications Benztropine (Cogentin) Trihexyphenidyl (Artane) Block acetylcholine, thus increasing dopamine May be effective against tremor, drooling; not much benefit for other PD symptoms Side effects: dry mouth, urinary retention, constipation Not a very good choice for elderly patients

4. Selegiline (Eldepryl) (Zelapar) Makes Sinemet last longer Zelapar is an orally disintegrating tablet Taken twice a day; Do not take later in day Lots of potential for drug interactions Useful for fatigue, but can over-stimulate Discuss the implications of the above information on counseling, side effects, and dosing.Discuss the implications of the above information on counseling, side effects, and dosing.

5. Rasagiline (Azilect) Makes Sinemet last longer More selective and more potent than selegiline Less drug interactions and side effects Once daily dosing No tyramine-potentiating effect No amphetamine-like effects Not yet available in USA Adverse effects in PRESTO trial were of the GI nature, (N/V) and �balance difficulties� In LARGO, rasagiline decreased �off� time by 1.18 hours (71 minutes) versus 0.4 hours (24 minutes) for placebo. No tyramine-potentiating effect No amphetamine-like effects Not yet available in USA Adverse effects in PRESTO trial were of the GI nature, (N/V) and �balance difficulties� In LARGO, rasagiline decreased �off� time by 1.18 hours (71 minutes) versus 0.4 hours (24 minutes) for placebo.

6. Amantadine (Symmetrel) Antiviral discovered by accident to be effective for PD May be effective in early PD, but also with Sinemet Side effects: dry mouth, urinary retention, constipation, rash on legs, leg swelling Use smaller doses for elderly patient What is this drug�s original classification?What is this drug�s original classification?

7. Carbidopa/Levodopa (Sinemet) Mainstay of Parkinson therapy since 1960s Converted to dopamine in the brain Most common side effects are: low blood pressure, dizziness, nausea, hallucinations, abnormal movements Levodopa crosses the BBB, whereas dopamine does not. If levodopa is converted to dopamine in the periphery, side effects such as N/V occur. Carbidopa prevents the conversion of levodopa in the periphery. If patient taking levodopa is experiencing nausea, may be able to add additional carbidopa (Lodosyn) 25 mg to their regimen to help control. Levodopa crosses the BBB, whereas dopamine does not. If levodopa is converted to dopamine in the periphery, side effects such as N/V occur. Carbidopa prevents the conversion of levodopa in the periphery. If patient taking levodopa is experiencing nausea, may be able to add additional carbidopa (Lodosyn) 25 mg to their regimen to help control.

8. Carbidopa Increases effectiveness of levodopa; allows more to get to brain Decreases side effects (nausea, low blood pressure) At least 75 mg daily is needed for maximum effectiveness

9. Carbidopa/Levodopa Dosing Take prior to meals (30-60 minutes) on empty stomach if possible Protein can decrease absorption Immediate-release and controlled-release (CR, ER) formulations are not absorbed identically

10. Carbidopa/Levodopa (Parcopa) Rapidly dissolving oral formulation; may work in as little as 5-10 minutes Benefits: patients who need early morning dose, have strict dosing schedules, or who have swallowing difficulties, tablets CAN be split Contains phenylalanine (artificial sweetener) May work in as little as 5-10 minutes per patient report.May work in as little as 5-10 minutes per patient report.

11. Catechol-O-methyltransferase (COMT) Inhibitors Tolcapone (Tasmar) Entacapone (Comtan) Make Sinemet last longer Adverse effects: Brownish/orange discoloration of urine, nausea, low blood pressure, abnormal movements, hallucinations, diarrhea What is the significance of �Little or no change in Cmax or Tmax with repeated doses?�What is the significance of �Little or no change in Cmax or Tmax with repeated doses?�

12. Carbidopa/Levodopa/Entacapone (Stalevo) New combination formulation Three strengths Stalevo 50: 12.5 mg carbidopa, 50 mg levodopa, 200 mg entacapone Stalevo 100: 25mg/100 mg/200 mg Stalevo 150: 37.5 mg/150 mg/200 mg Drawbacks: cost, difficult to adjust doses

13. Dopamine Agonist Agents Looks like dopamine to the brain Can use with or instead of Sinemet Side Effects: Nausea, confusion, hallucinations, �sleep attacks,� low blood pressure Problems with impulse control reported, obsessive compulsive behaviors

14. Dopamine Agonist Agents Ergots Bromocriptine (Parlodel) Pergolide (Permax) Not favored as much as newer agents Non-ergots Ropinirole (Requip) Pramipexole (Mirapex) Rotigotine (Neupro) Patch

15. Neupro Patch Recall March 21, 2008 Neupro� patients - please consult your physician as soon as possible Dear Patient, Neupro� (rotigotine transdermal system) patches are being recalled in the United States and will not be available after the end of April 2008. The Neupro� patch is a transdermal delivery system worn on the skin and is used to treat early stage Parkinson's disease. It is made by Schwarz Pharma, a company of the UCB group. You should take the following steps: Do not stop taking Neupro without first talking to your doctor Consult your physician as soon as possible Your doctor will instruct you on how to gradually come off Neupro � this may take several days, depending on your current dose. Some Neupro patches have snowflake-like patterns on them. The more snowflakes you see, the less likely it is that the patch will work properly.

16. Apomorphine (Apokyn) Injectable dopamine agonist approved for the acute, intermittent treatment of �off� episodes Common side effects: injection site reaction, NAUSEA (SIGNIFICANT), dizziness, sedation, hallucinations, peripheral edema Should be used PRN. Should NOT be administered IV. Can crystallize and cause PE. Can cause sexual stimulation/increased libido. Has been studied as a potential treatment for erectile dysfunction in men. Trimethobenzamide is to be used in conjunction with apomorphine to counteract the N/V. 5-HT3 antagonists such as Zofran are contraindicated d/t profound drops in blood pressure and loss of consciousness in patients taking the combination. Other antiemetics such as prochlorperazine cannot be used due to their dopaminergic blocking effects and worsening of Parkinson�s symptoms.Should be used PRN. Should NOT be administered IV. Can crystallize and cause PE. Can cause sexual stimulation/increased libido. Has been studied as a potential treatment for erectile dysfunction in men. Trimethobenzamide is to be used in conjunction with apomorphine to counteract the N/V. 5-HT3 antagonists such as Zofran are contraindicated d/t profound drops in blood pressure and loss of consciousness in patients taking the combination. Other antiemetics such as prochlorperazine cannot be used due to their dopaminergic blocking effects and worsening of Parkinson�s symptoms.

17. Night Time Dosing If tremor prevents sleep Off time is uncomfortable or can�t go to bathroom Restless leg syndrome May need a dose before getting out of bed

18. Missed Doses Take as soon as you remember If less than an hour off, can probably resume regular schedule Otherwise, may need to spread out the other doses If close to bedtime, skip

19. Overdose? Eldepryl and Azilect might present most problems Exaggerated side effects Most meds last only a short time Call the doctor or pharmacist if you are worried

20. Drug Interactions Avoid these anti-nausea drugs: Phenergan, Reglan, Compazine Most antipsychotics (used for shizophrenia or Alzheimer�s): Haldol, Thorazine, Mellaril, Risperdal, Zyprexa Seroquel may be the best antipsychotic if a Parkinson patient needs one

21. Over-the-Counter Medications Most are okay with Parkinson meds Cough suppressant (dextromethorphan) might interact with Eldepryl or Azilect Best to stick to products that contain only a single ingredient Any questions, ask the pharmacist