The CR form is absorbed from the intestine into the blood slowly and can be useful for people with Parkinson’s disease who respond well to Sinemet but need to prolong the number of hours of benefit from each dose. 1 Sinemet CR 50/200 alone at 6pm. This situation rarely, if ever, occurs in PSP. The mean peak concentration of levodopa following administration of one 'Half Sinemet CR' tablet was greater than 50% of that following one 'Sinemet CR' tablet. Dosage adjustment of 'Sinemet CR' or 'Half Sinemet CR' may be necessary when these agents are added to an existing treatment regimen for 'Sinemet CR' or 'Half Sinemet CR'.Patients should be observed carefully if abrupt reduction or discontinuation of 'Sinemet CR' or 'Half Sinemet CR' is required, especially if the patient is receiving antipsychotics (see 4.4 'Special warnings and precautions for use').Safety and effectiveness of 'Sinemet CR' or 'Half Sinemet CR' in infants and children have not been established, and its use in patients below the age of 18 is not recommended. I can't speak for anyone else but this works for me. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with levodopa. Use of 'Sinemet CR' with dopamine-depleting agents (e.g., tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone (See 4.3 'Contraindications').Since levodopa competes with certain amino acids, the absorption of levodopa may be impaired in some patients on a high protein diet.The effect of simultaneous administration of antacids with 'Sinemet CR' or 'Half Sinemet CR' on the bioavailability of levodopa has not been studied.There are insufficient data to evaluate the possible harmfulness of this substance when used in human pregnancy (See 5.3 'Preclinical Safety Data'). © Merck Sharp & Dohme Limited 2017. The advanced form of motor fluctuations ('on-off' phenomenon) is characterised by unpredictable swings from mobility to immobility.
'Sinemet CR': peach-coloured, oval shaped, biconvex tablets, one side deep-scored and the other marked '521'. Higher doses (up to 12 tablets) and shorter intervals (less than four hours) have been used, but are not usually recommended.When doses of 'Sinemet CR' are given at intervals of less than four hours, or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day. 4.5 Interaction with other medicinal products and other forms of interaction6.6 Special precautions for disposal and other handling9. The most common side effect in patients with Parkinson’s disease, involuntary writhing movements “chorea” or dyskinesias) occur very rarely in PSP, even at high Sinemet dosages.Patients with PSP should generally receive the standard Sinemet (or generic levodopa/carbidopa) preparation rather than the controlled-release (Sinemet CR or generic levodopa/carbidopa ER) form.
The most common side effects of Sinemet in patients with PSP are confusion, hallucinations and dizziness. Initial dosages should not exceed 600 mg per day of levodopa, nor be given at intervals of less than six hours.Following initiation of therapy, doses and dosing intervals may be increased or decreased, depending upon therapeutic response. The bioavailability may be influenced by drugs which affect the gastro-intestinal propulsion.The medicine has appeared harmful in animal trials (visceral and skeletal malformations in rabbits). Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App StoreManagement of acute overdosage with 'Sinemet CR' or 'Half Sinemet CR' is basically the same as management of acute overdosage with levodopa; however, pyridoxine is not effective in reversing the actions of 'Sinemet CR' or 'Half Sinemet CR'.Electrocardiographic monitoring should be instituted and the patient observed carefully for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. These reactions are thought to be due to increased brain dopamine following administration of levodopa and use of 'Sinemet CR' or 'Half Sinemet CR' may cause recurrence. The incidence of dyskinesias is slightly higher during treatment with 'Sinemet CR' than with conventional 'Sinemet' (16.5% vs 12.2%) in advanced patients with motor fluctuations. Because Sinemet CR is sometimes absorbed very little or erratically, a poor CR response in a patient with PSP might be incorrectly blamed on the fact that the disease is usually unresponsive to the drug. The occurrence of dyskinesias may require dosage reduction.

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