SINEMET CR 50/200 TABLET

TABLET

**DOSAGE & ADMINISTRATION** SINEMET CR tablets contain a 1:4 ratio of carbidopa to levodopa. SINEMET CR 50/200 contains carbidopa 50 mg/levodopa 200 mg per tablet. SINEMET CR 25/100, the half-strength formulation, contains carbidopa 25 mg/levodopa 100 mg per tablet. The daily dosage of SINEMET CR must be determined by careful titration. Patients should be monitored closely during the dose adjustment period, particularly with regard to appearance or worsening of nausea or abnormal involuntary movements, including dyskinesias, chorea and dystonia. SINEMET CR 50/200 may be administered as whole or as half tablets. SINEMET CR 25/100 should only be administered as whole tablets. So that the controlled release properties of the products can be maintained, tablets should not be chewed or crushed. Standard antiparkinson drugs, other than levodopa alone, may be continued while SINEMET CR is being administered, although their dosage may have to be adjusted. Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, SINEMET CR can be given to patients receiving supplemental pyridoxine (vitamin B6). INITIAL DOSAGE Patients Who Have Not Received Prior Levodopa Therapy SINEMET CR 25/100 is designed to be used primarily in early stage patients who have not had prior levodopa therapy or to facilitate titration when necessary in patients receiving SINEMET CR 50/200. The initial recommended dose is 1 tablet of SINEMET CR 25/100 twice daily. For patients who require more levodopa, a daily dose of 1 to 4 tablets of SINEMET CR 25/100 twice a day is generally well-tolerated. When appropriate, levodopa therapy may also be initiated with SINEMET CR 50/200. The initial recommended dose is 1 tablet of SINEMET CR 50/200 two or three times daily. Initial dosages should not exceed 600 mg per day of levodopa or be given at intervals of less than 6 hours. Patients Currently Treated with Conventional Levodopa/Decarboxylase Inhibitor Combinations Dosage with SINEMET CR 50/200 should be substituted at an amount that provides approximately 10% more levodopa per day, although this may need to be increased to a dosage that provides up to 30% more levodopa per day depending on clinical response (see DOSAGE and ADMINISTRATION, Titration). The interval between doses of SINEMET CR 50/200 should be 4–8 hours during the waking day. A guide for substitution of SINEMET CR 50/200 treatment for conventional levodopa/decarboxylase inhibitor combinations is shown in the table below:  SINEMET CR 25/100 is available to facilitate titration when 100 mg steps are required and as an alternative to the half tablet of SINEMET CR 50/200. Patients Currently Treated With Levodopa Alone Levodopa must be discontinued at least eight hours before therapy with SINEMET CR 50/200 is started. In patients with mild to moderate disease, the initial recommended dose is 1 tablet of SINEMET CR 50/200 two or three times daily. TITRATION Following initiation of therapy, doses and dosing intervals may be increased or decreased, depending upon therapeutic response. Most patients have been adequately treated with 2 to 8 tablets of SINEMET CR 50/200 per day, administered as divided doses at intervals ranging from 4 to 12 hours during the waking day. Higher doses (up to 12 tablets) and shorter intervals (less than 4 hours) have been used, but are not usually recommended. When doses of SINEMET CR 50/200 are given at intervals of less than 4 hours, or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day. In some patients the onset of effect of the first morning dose may be delayed for up to 1 hour compared with the response usually obtained from the first morning dose of SINEMET. An interval of at least 3 days between dosage adjustments is recommended. MAINTENANCE Because Parkinson's disease is progressive, periodic clinical evaluations are recommended and adjustment of the dosage regimen of SINEMET CR may be required. ADDITION OF OTHER ANTIPARKINSON MEDICATIONS Anticholinergic agents, dopamine agonists and amantadine can be given with SINEMET CR. Dosage adjustment of SINEMET CR may be necessary when these agents are added to an existing treatment regimen for SINEMET CR. A dose of SINEMET 10/100 or 25/100 (one half or a whole tablet) can be added to the dosage regimen of SINEMET CR in selected patients with advanced disease who need additional levodopa for a brief time during daytime hours. INTERRUPTION OF THERAPY Patients should be observed carefully if abrupt reduction or discontinuation of SINEMET CR is required, especially if the patient is receiving neuroleptics (see PRECAUTIONS – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). If general anesthesia is required, SINEMET CR may be continued as long as the patient is permitted to take oral medication. If therapy is interrupted temporarily, the usual dosage should be administered as soon as the patient is able to take oral medication.