Drug Detail:Sinemet cr (Carbidopa and levodopa [ kar-bi-doe-pa-and-lee-voe-doe-pa ])
Generic Name: carbidopa 25mg, levodopa 100mg
Dosage Form: tablet, extended release
Drug Class: Dopaminergic antiparkinsonism agents
SINEMET CR contains carbidopa and levodopa in a 1:4 ratio as either the 50-200 tablet or the 25-100 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 involuntary movements, dyskinesias or nausea. SINEMET CR should not be chewed or crushed.
Standard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly 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 currently treated with conventional carbidopa levodopa preparations: Studies show that peripheral dopa-decarboxylase is saturated by the bioavailable carbidopa at doses of 70 mg a day and greater. Because the bioavailabilities of carbidopa and levodopa in SINEMET and SINEMET CR are different, appropriate adjustments should be made, as shown in Table 2.
| Tablet | Amount of Levodopa (mg) in Each Tablet |
Approximate Bioavailability |
Approximate Amount of Bioavailable Levodopa (mg) in Each Tablet |
|---|---|---|---|
|
|||
| SINEMET CR 50-200 |
200 |
0.70-0.75† |
140-150 |
| SINEMET 25-100 |
100 |
0.99‡ |
99 |
Dosage with SINEMET CR 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 with SINEMET CR). The interval between doses of SINEMET CR should be 4-8 hours during the waking day. (See CLINICAL PHARMACOLOGY, Pharmacodynamics.)
A guideline for initiation of SINEMET CR is shown in Table 3.
|
|
| SINEMET Total Daily Dose* Levodopa (mg) |
SINEMET CR Suggested Dosage Regimen |
| 300-400 | 200 mg b.i.d. |
| 500-600 | 300 mg b.i.d. or 200 mg t.i.d. |
| 700-800 | A total of 800 mg in 3 or more divided doses (e.g., 300 mg a.m., 300 mg early p.m., and 200 mg later p.m.) |
| 900-1000 | A total of 1000 mg in 3 or more divided doses (e.g., 400 mg a.m., 400 mg early p.m., and 200 mg later p.m.) |
Patients currently treated with levodopa without a decarboxylase inhibitor: Levodopa must be discontinued at least twelve hours before therapy with SINEMET CR is started. SINEMET CR should be substituted at a dosage that will provide approximately 25% of the previous levodopa dosage. In patients with mild to moderate disease, the initial dose is usually 1 tablet of SINEMET CR 50-200 b.i.d.
Patients not receiving levodopa: In patients with mild to moderate disease, the initial recommended dose is 1 tablet of SINEMET CR 50-200 b.i.d. Initial dosage should not be given at intervals of less than 6 hours.
Titration with SINEMET CR
Following initiation of therapy, doses and dosing intervals may be increased or decreased depending upon therapeutic response. Most patients have been adequately treated with doses of SINEMET CR that provide 400 to 1600 mg of levodopa per day, administered as divided doses at intervals ranging from 4 to 8 hours during the waking day. Higher doses of SINEMET CR (2400 mg or more of levodopa per day) and shorter intervals (less than 4 hours) have been used, but are not usually recommended.
When doses of SINEMET CR are given at intervals of less than 4 hours, and/or if the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day.
An interval of at least 3 days between dosage adjustments is recommended.
Maintenance
Because Parkinson's disease is progressive, periodic clinical evaluations are recommended; 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.
A dose of carbidopa levodopa immediate release 25-100 or 10-100 (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 immediate-release levodopa for a brief time during daytime hours.
Interruption of Therapy
Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of SINEMET or SINEMET CR.
Patients should be observed carefully if abrupt reduction or discontinuation of SINEMET CR is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)
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 patient should be observed for symptoms resembling NMS, and the usual dosage should be administered as soon as the patient is able to take oral medication.
