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Parkinson's Treatment “Tips & Pearls”

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Parkinson's Treatment “Tips & Pearls” Parkinson's Treatment “Tips & Pearls” June 2005 The RxFiles Academic Detailing Program Objective Comparisons for Optimal Drug Therapy Saskatoon City Hospital 701 Queen Street, Saskatoon, SK S7K 0M7 Phone 306-655-8506 ; Fax 306-655-7980; www.RxFiles.ca How to identify Parkinson's disease? Are there drawbacks to dopamine agonists? Parkinsonism (PS) is a clinical diagnosis that requires 2 of Although not as potent as LD, younger patients may benefit the following 3: bradykinesia, rigidity & resting tremor (or from using dopamine agonists (DA) to delay LD tolerance and the THREE S's: slow, stiff & shaky). Postural instability is dyskinesia. DA's have less motor complications, but more often a late PD presentation. The majority ~85% of PS cases hallucinations, somnolence & edema than LD. If DAs are are idiopathic Parkinson's disease (PD). Other PS variants not titrated both slowly and up to the therapeutic dose, side include multiple system atrophy, progressive supranuclear effects occur without much clinical benefit. palsy and drug-induced PS. Lewy body dementia has PS onset within the first year Are anticholinergics in the elderly a good idea? features with dementia . Drug benefits must but unproven superiority be evaluated against any side effects to ensure benefits Although useful for tremor predominant PD , outweigh the risks. Individualize therapy! mild PD symptoms, drooling and dystonia, use in the elderly frequently causes constipation, confusion, and What medications can induce PS? hallucinations. If stopping anticholinergics, taper to prevent Select medications can induce PS either acutely or within 3 PD exacerbations. Using lower doses minimizes toxicity. months of use (eg. amiodarone, amphotericin B, calcium How to manage a psychotic PD patient? channel blockers, chemotherapy, lithium, meperidine, metoclopramide, neuroleptics, cholinergics, reserpine, It is important to rule out drug induced confusion/hallucinations. SSRI's & valproate). After the offending drug is stopped it In general decrease the dose, or discontinue the drug in the may take up to 2-6 months for PS symptoms to resolve. following order: anticholinergic, selegiline, amantadine, DA & then levodopa. Consider quetiapine after other offending drugs Is levodopa still the most powerful med? are stopped. It may take 1-4 weeks for psychosis to resolve. Levodopa (LD) provides superior motor benefit, but is (Alternately clozapine but requires weekly blood tests, expensive & lacks coverage for this indication SK.) associated with increased dyskinesias. In early PD, LD use is How to manage behavior in a PD patient? often delayed to preserve LD usefulness, but LD is very Antidepressants (eg. tricyclics,SSRI's) may be required for valuable in the elderly. Other early PD considerations are depression, but rare cases of SSRI's worsening PD are reported. amantadine or selegiline. Initial Sinemet dose is usually 100/25mg bid, increasing in ~1week if needed. An adequate trial How to manage wearing off effects in PD patient? dose is considered to be ≤200/50mg qid x 3 months. Consider smaller & more frequent LD dosing (liquid forms an option), an addition of Sinemet CR, combination DA & How can I get the Sinemet to work faster? LD, entacapone, amantadine, selegiline, apomorphine SC or Chewing the tablets or drinking with carbonated beverages possibly decreasing protein in the diet may help. (IF adding will increase absorption (whereas high protein foods may DA or entacapone a decrease in LD dose may be needed.) slow absorption). Clinically this is useful for patients with severe early morning symptoms and/or painful dystonia. How to manage dyskinesia in a PD patient? Dyskinesias are best prevented by avoiding large doses of LD Ways to overcome troubling LD side effects? early in the disease. Treat if bothersome; consider lowering LD Nausea: ensure 75-200mg of carbidopa is being used with dose (CR form hard to adjust dose), add amantadine, add/↑/switch to a LD, LD with food or consider using domperidone 5-10mg po tid ac. DA, possibly stop entacapone or selegiline or consider surgery. Hypotension: ensure adequate water & salt intake; consider How about alternative therapies? midodrine 7.5-15mg/d, domperidone or fludrocortisone 0.05-0.4mg/d. Lack evidence for benefit for vitamins, herbs or chelation; Cowhage Is Sinemet CR best for my patient? however, broad beans do contain LD. PS documented with There is no evidence that CR levodopa is better than regular manganese, but only "shakes" from lead or mercury. PD seems to release, but it is more costly. However, if early morning have a genetic predisposition with environmental factors playing "off" episodes are occurring, giving CR at bedtime may a role. Benefits of Coenzyme Q10 in PD requires further study. We would like to acknowledge the following contributors and reviewers: Dr. Alex Rajput (SHR-Neurology), help. Taking with food increases absorption, but overall only Dr. Tejal Patel (RQHR-Pharmacy) & the RxFiles Advisory Committee. B. Jensen BSP, L. Regier BSP, BA DISCLAIMER: The content of this newsletter represents the research, experience and opinions of the authors and not those of the Board or Administration of Saskatoon Health 70% is bioavailable (eg. ↑ dose by 20-30% if switching to Region (SHR). Neither the authors nor Saskatoon Health Region nor any other party who has been involved in the preparation or publication of this work warrants or represents that the information contained herein is accurate or complete, and they are not responsible for any errors or omissions or for the result obtained from the use of such information. Any use of the newsletter will imply acknowledgment of this disclaimer and release any responsibility of SHR, its employees, servants or agents. Readers are encouraged to confirm the information CR from regular release, if an equivalent dose is desired). contained herein with other sources. Copyright 2005 – RxFiles, Saskatoon Health Region (SHR) www.RxFiles.ca PARKINSON'S DISEASE (PD) – Drug Comparison Chart 1,2,3,4,5,6 Brent Jensen BSP - www.RxFiles.ca June 05 Generic/TRADE Class/Mechanism of Action/ Side effects / = Therapeutic Use / Comments / INITIAL & USUAL DOSE $ 7 (Strength & forms) Pregnancy category Contraindications CI Drug Interactions DI MAX DOSE RANGE /30d P 50/12.5mg bid 100/25mg tid-qid cc 54-70 Levodopa/benserazide Common: GI: nausea, vomiting, idiopathic, postencephalitic & symptomatic ↑ 200/50mg tid cc 87 PROLOPA =P anorexia; CNS: headache, confusion, PD esp. if pt rigid, bradykinesia or elderly. Not q3-7d Max 2g/d (contains phenylalanine) 50/12.5, 100/25, 200/50mg cap dizziness, hallucinations, mood useful for freezing. For restless leg sx (eg. 100/25@hs). changes, nightmares, insomnia, 100/25mg tid-qid cc Levodopa/carbidopa 8 Dopamine precursor: -initiate PD tx with either levodopa or a DA; S 50/12.5mg bid 45-58 depression; rash, alopecia, discolored ↑q3-7d Max 2g/d 250/25mg tid cc 49 SINEMET/generic =S Levodopa (LD): most potent ↑ levodopa provides superior motor benefit but is ς ς ς urine, dark saliva/sweat & libido. 1 American 2002 100/25mg CR tid cc 76 100/10 ,100/25 ,250/25 mg IR tab; med available for PD Dose unresponsiveness & freezing, assoc. with an ↑risk of dyskinesia. ς Dosing frequency 200/50mg CR bid-tid cc 60-86 100/25,200/50mg CR tab: {regular tab/cap: peak level at fluctuations (wearing off, on-off), -wearing off, on-off phenomena, sudden offs & is 3-6x/day for Chew tabs & carbonated 70% bioavailable vs immediate release ~30minutes & ~4hr duration} dyskinesia (chorea, peak dose, freezing & dyskinesia incl. painful dystonia affect regular release. drink will ↑absorption even Oral liquid form 9,10 diphasic & dystoniaoff period; hand/foot in AM). 15 ↓ ≤ 70% of pts within 5yr of starting levodopa. An adequate trial useful for IR tab esp. good for manufactured by some pharmacies Benserazide & carbidopa Serious: dyskinesia, BP, psychosis, 16 (Koller) arrhythmias, sudden sleep, blood -No evidence that CR levodopa better than is often ~3months of severe early morning Sx. carbidopa/levodopa/ are peripheral dopamine dyscrasia, neuroleptic malignant regular release, but may help to give CR @HS if 200/50mg qid, but ↑ 18 entacapone STALEVO 11 decarboxylation inhibitors syndrome (esp. after abrupt D/C early morning OFF episodes occurring most pts. respond to protein foods -not in yet which ↓ nausea from levodopa. med), malignant melanoma, anemia lower dosages. may ↓ absorption. ≥ 14 ↑ -on-off phenomenon (reduced by giving smaller, 50= 12.5/50/200 ( 75mg carbidopa blocks & possible gambling behavior. ↑ dose by 20-30% Take cc if nausea; enzyme; may need up to 200mg) CI: MAOI use, caution if psychosis more frequent levodopa doses or adding DA) 100= 25/100/200 if switching to ac for ↑ absorption history, glaucoma,sympathomimetic -can be given up to 4hrs before surgery 150= 37.5/150/200mg tab CR if want of regular formulation amines & may activate melanoma. -may slow progression or ↓ severity of sx (NEJM'04) 17 (don't cut these doses in half) C -all equivalent dose. Correct ↓BP SE by: ↑water & salt → (PARCOPA: rapid dissolving form of -avoid abrupt withdrawal worsen PD/cause NMS CR useful 5-10-20mg tid ac 7.5-30mg/d Domperidone ~20 12 intake, midodrine , ↓ levo/carbidopa avail in USA only , DI: ↓ effect of levodopa: antipsychotics, iron absorption , sometimes since ↓ 0.05-0.4mg/d to nausea / hypotension DUODOPA: levo/carbidopa gel for domperidone,fludrocortisone isoniazid, metoclopramide & pyridoxine only if levodopa alone ; no duration of action 13 & adjust antihypertensive
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