AAN GUIDELINES Bundle

Levodopa carbidopa 1 /levodopa Parcopa 10/100, 25/100, 25/250 mg orally disintegrating immediate release tablets Initial: 25/100 mg tid; titrate up by 25/100 mg/d or every other day until 200/800 mg/d OR 10/100 mg tid-qid; titrate up by 10/100 mg/d or every other day until 20/200 mg qid Maintenance: ≥ 70-100 mg/d carbidopa to max 200 mg/d > Contraindicated with use of nonselective MAOIs, in narrow-angle glaucoma > Caution if history of melanoma, of psychoses, or of cardiac, pulmonary, renal, hepatic, or endocrine disease > If transferring from levodopa alone, discontinue levodopa 12-24 h before starting carbidopa/levodopa (25% of previous levodopa dosage) > Abrupt dose reduction or discontinuation may cause neuroleptic malignant syndrome Sinemet, generics Sinemet CR, generics 10/100, 25/100, 25/250 mg immediate release tablets 25/100, 50/200 mg sustained release tablets Initial: 25/100 mg tid; titrate up by 25/100 mg/d or every other day until 200/800 mg/d Maintenance: ≥ 70-100 mg/d carbidopa to max 200 mg/d Initial: 50/200 mg bid (≥6 h); titrate up (q ≥ 3 d) until 400-1600 mg/d levodopa in divided doses 4-8 h > Contraindicated in patients with melanoma carbidopa 1 /levodopa/ entacapone 2 Stalevo 12.5/50/200, 25/100/200, 37.5/150/200 mg tablets Follow dosage for immediate release carbidopa/levidopa above (only one tablet per dose) to max 1600 mg/d entacapone > Intended to replace immediate release carbidopa/levidopa (without entacapone) therapy if patient experiences end-of-dose "wearing off" with total daily dose of < _ 600 mg levodopa without dyskinesia OR to switch patients on entacapone and carbidopa/levodopa as separate drugs onto one drug > See comments above for carbidopa/levodopa and entacapone > Cannot be used with entacapone nor can more than one tablet be taken at one time > Contraindicated in patients with melanoma Table partially constructed from individual drug Prescribing Information labeling. * 3/29/2007 FDA announces voluntary withdrawal of pergolide products 1. Carbidopa added to levodopa reduces peripheral effects (e.g., nausea, vomiting) of levodopa but does not decrease CNS effects (e.g., dyskinesia, akinesia) of levodopa. 2. Entacapone in conjunction with levodopa and carbidopa produces greater and more sustained plasma levels of levodopa than after administration of levodopa and carbidopa alone. ese more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson disease. Higher levodopa levels may also lead to increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. NOTE: e transdermal patch was not available for delivering medication when the original guideline was written. **Recommendations are based only on evidence available in the literature and are limited by the quality of the studies reviewed. Studies are limited in recommendations of one drug over another. C OMT (catechol-O-methyl transferase) inhibitors entacapone Comtan 200 mg tablet 200 mg concomitant with each carbidopa/levodopa dose to max 1600 mg/d > Use only as adjunct to carbidopa/levodopa therapy for "wearing off" episodes > Avoid concomitant use with non-selective MAOIs, but may be taken with selective MAO-B inhibitor > Caution if hepatic impairment > Orthostatic hypotension, syncope, diarrhea, hallucinations, dyskinesia tolcapone Tasmar 100, 200 mg tablets 100 mg tid (1st dose concomitant with 1st dose carbidopa/levodopa, subsequent doses 6 and 12 hr later) 200 mg tid if anticipated incremental clinical benefit justified > Use only as adjunct to carbidopa/levodopa therapy if symptom fluctuations and unsatisfactory response to or inappropriate candidate for other adjunctive therapies > Should not be used by patients without a complete discussion of risks and patient has provided written acknowledgement that the risks have been explained > Because of the risk of liver injury, withdraw from therapy if no substantial clinical benefit is seen within 3 weeks > Test with serum ALT/AST before starting therapy, every 2–4 wk as clinically indicated for 6 mo, and thereafter as clinically indicated > Avoid concomitant use with non-selective MAOIs, but may be taken with selective MAO-B inhibitor > Orthostatic hypotension, syncope, diarrhea, hallucinations, dyskinesia Recommendations for medications that reduce off time for patients with motor fluctuations: Î Offer: > Entacapone > Rasagiline Î Consider: > Pergolide (use with caution; requires monitoring for valvular fibrosis) > Pramipexole > Ropinirole > Tolcapone (use with caution; requires monitoring for hepatoxicity) > Zelapar Adapted from: American Academy of Neurology (AAN) Summary of Evidence-based Guideline for Clinicians Î See product labeling for complete prescribing information. Î Medications are symptomatic and not considered neuroprotective. Î Medications to reduce off time in patients with motor f luctuations:** Table 3. Pharmacotherapeutic Options for Symptomatic Treatment of Parkinson Disease (continued)

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