Sinemet 25/100/Sinemet 25/250

Sinemet 25/100/Sinemet 25/250

carbidopa + levodopa

Manufacturer:

M & H Manufacturing

Distributor:

B L H Trading
Full Prescribing Info
Contents
Carbidopa, levodopa.
Description
Sinemet 25/100: Each tablet contains carbidopa 25 mg and levodopa 100 mg.
Sinemet 25/250: Each tablet contains carbidopa 25 mg and levodopa 250 mg.
Action
Sinemet is a combination of carbidopa, an aromatic amino acid decarboxylase inhibitor, and levodopa, the metabolic precursor of dopamine, for the treatment of Parkinson's disease and syndrome.
Levodopa relieves the symptoms of Parkinson's disease by being decarboxylated to dopamine in the brain. Carbidopa, which does not cross the blood-brain barrier, inhibits the extracerebral decarboxylation of levodopa, making more levodopa available for transport to the brain and subsequent conversion to dopamine.
Sinemet improves overall therapeutic response as compared to levodopa. Sinemet provides effective long-lasting levodopa plasma levels at doses that are approximately 80% lower than those needed with levodopa alone.
While pyridoxine HCl (vitamin B6) is known to accelerate the peripheral metabolism of levodopa to dopamine, carbidopa prevents this action.
Indications/Uses
Treatment of Parkinson's disease and syndrome. It is useful in relieving many of the symptoms of parkinsonism, particularly rigidity and bradykinesia. Sinemet frequently is helpful in the management of tremor, dysphagia, sialorrhea and postural instability associated with Parkinson's disease and syndrome.
When therapeutic response to levodopa alone is irregular, and signs and symptoms of Parkinson's disease are not evenly controlled throughout the day, substitution of Sinemet usually is effective in reducing fluctuations in response.
By reducing certain adverse reactions produced by levodopa alone, Sinemet permits more patients to obtain adequate relief of the symptoms of Parkinson's disease.
Sinemet is also indicated for patients with Parkinsonism who are taking vitamin preparations that contain pyridoxine HCl (vitamin B6).
Dosage/Direction for Use
The optimum daily dosage of Sinemet must be determined by careful titration in each patient. Sinemet tablets are available in a 1:4 ratio of carbidopa to levodopa (Sinemet 25/100) as well as a 1:10 ratio (Sinemet 25/250). Tablets of the 2 ratios may be given separately or combined as needed to provide the optimum dosage.
Each tablet of Sinemet is designed to be divided in ½ with minimal pressure.
General Considerations: Dosage should be titrated to individual patient needs and this may require adjusting both the individual dose and the frequency of administration.
Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70-100 mg/day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
Usual Initial Dosage: Dosage is best initiated with 1 tab of Sinemet 25/100 3 times/day. This dosage schedule provides carbidopa 75 mg/day. Dosage may be increased by 1 tab everyday or every other day, as necessary, until a dosage equivalent of 8 tabs of Sinemet 25/100 a day is reached.
For patients starting with Sinemet 25/250, the initial dose is ½ tab taken once or twice daily. However, this may not provide the optimal amount of carbidopa needed by many patients. If necessary, add ½ tab everyday or every other day until optimal response is reached.
Fully effective doses usually are reached within 7 days as compared to weeks or months with levodopa alone.
Maintenance: Therapy should be individualized and adjusted according to the desired therapeutic response. At least 70-100 mg of carbidopa/day should be provided for optimal inhibition of extracerebral decarboxylation of levodopa.
When more levodopa is required, Sinemet 25/250 should be substituted for Sinemet 25/100. If necessary, the dosage of Sinemet 25/250 may be increased by ½ or 1 tab everyday or every other day to a maximum of 8 tabs a day. Experience with total daily dosages of carbidopa >200 mg is limited.
Maximum Recommended Dose: 8 tabs of Sinemet 25/250/day (carbidopa 200 mg and levodopa 2 g). This is about 3 mg/kg of carbidopa and 30 mg/kg of levodopa in a patient weighing 70 kg.
Contraindications
Monoamine oxidase (MAO) inhibitors (except low doses of selective MAO-B inhibitors) and Sinemet should not be given concomitantly. These inhibitors must be discontinued at least 2 weeks prior to initiating therapy with Sinemet.
Sinemet is contraindicated in patients with known hypersensitivity to this drug and in patients with narrow-angle glaucoma.
Since levodopa may activate a malignant melanoma, Sinemet should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.
Special Precautions
Sinemet may be given to patients already receiving levodopa alone; however, the levodopa alone must be discontinued at least 12 hrs before Sinemet is started. Sinemet should be substituted at a dosage that will provide approximately 20% of the previous levodopa dosage (see Dosage & Administration).
Sinemet is not recommended for the treatment of drug-induced extrapyramidal reactions.
Sinemet should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.
As with levodopa, care should be exercised in administering Sinemet to patients with a history of myocardial infarction who have atrial, nodal or ventricular arrhythmia. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment.
All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, or other serious antisocial behavior.
As with levodopa, Sinemet may cause involuntary movements and mental disturbances. Patients with current or a history of severe involuntary movements or psychotic episodes should be monitored carefully. These reactions are thought to be due to increased brain dopamine.
A symptom complex resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, mental changes and increased serum creatine phosphokinase has been reported when antiparkinsonian agents were withdrawn abruptly. Therefore, patients should be observed carefully when the dosage of Sinemet is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
Caution should be exercised with concomitant administration of psychoactive drugs and Sinemet (see Interactions). Patients with a history of convulsion should be treated with caution.
Patients with chronic wide-angle glaucoma may be treated cautiously with Sinemet, provided the intraocular pressure is well controlled and the patient monitored carefully for changes in intraocular pressure during therapy.
As with levodopa, there is a possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.
If general anesthesia is required, Sinemet should be discontinued for at least 6-8 hrs prior to anesthetic procedure. Sinemet may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the usual daily dosage may be administered as soon as the patient is able to take oral medication.
Use in pregnancy & lactation: The effects of Sinemet on human pregnancy and lactation are unknown. Both levodopa and combination of levodopa and carbidopa have caused visceral and skeletal malformation in experimental animals. Therefore, use of Sinemet during pregnancy requires that the anticipated benefits of the drug be weighed against possible hazards.
Sinemet should not be given to nursing mothers.
Use in children: The safety of Sinemet in patients <18 years has not been established.
Use In Pregnancy & Lactation
The effects of Sinemet on human pregnancy and lactation are unknown. Both levodopa and combination of levodopa and carbidopa have caused visceral and skeletal malformation in experimental animals. Therefore, use of Sinemet during pregnancy requires that the anticipated benefits of the drug be weighed against possible hazards. Sinemet should not be given to nursing mothers.
Side Effects
Side effects that occur frequently in patients receiving Sinemet are those due to the central neuropharmacologic activity of dopamine. These reactions usually can be diminished by dosage reduction. The most common side effects are dyskinesias, including choreiform, dystonic and other involuntary movements. Muscle twitching and blepharospasm may be taken as early signs to consider dosage reduction.
Other serious side effects are mental changes, including paranoid ideation and psychotic episodes; depression with or without development of suicidal tendencies; and dementia. A common but less serious side effect is nausea.
Less frequent side effects are cardiac irregularities and/or palpitation, orthostatic hypotensive episodes, bradykinetic episodes (the "on-off" phenomenon), anorexia, vomiting, dizziness and somnolence.
Gastrointestinal bleeding, development of duodenal ulcer, hypertension, phlebitis, leukopenia, hemolytic and nonhemolytic anemia, thrombocytopenia, agranulocytosis, chest pain, dyspnea and paresthesia have occurred rarely.
Occasionally, convulsions have occurred; however, a causal relationship with Sinemet has not been established.
Laboratory Tests: Transient abnormalities in laboratory tests which, however, have not been associated with clinical evidence of disease, include elevations of blood urea nitrogen, SGOT, SGPT, LDH, bilirubin, alkaline phosphatase or protein-bound iodine.
Decreased hemoglobin and hematocrit, elevated serum glucose, and white blood cells, bacteria and blood in the urine have been reported.
Commonly, levels of blood urea nitrogen, creatinine and uric acid are lower during administration of Sinemet than with levodopa.
Positive Coombs' tests have been reported both with Sinemet and with levodopa alone, but hemolytic anemia is extremely rare.
Sinemet may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose-oxidase methods of testing for glucosuria.
Other side effects that have been reported with levodopa are:
Nervous System: Ataxia, numbness, increased hand tremor, muscle twitching, blepharospasm, muscle cramps, trismus, activation of latent Horner's syndrome.
Psychiatric: Confusion, sleepiness, insomnia, nightmares, hallucinations, delusions, agitation, anxiety, euphoria.
Gastrointestinal: Dry mouth, bitter taste, sialorrhea, dysphagia, bruxism, hiccups, abdominal pain and distress, constipation, diarrhea, flatulence, burning sensation of tongue.
Metabolic: Weight gain or loss, edema.
Integumentary: Flushing, increased sweating, dark sweat, rash, hair loss.
Genitourinary: Urinary retention, urinary incontinence, dark urine, priapism.
Special Senses: Diplopia, blurred vision, dilated pupils and oculogyric crises.
Miscellaneous: Weakness, faintness, fatigue, headache, hoarseness, malaise, hot flashes, sense of stimulation, bizarre breathing patterns, neuroleptic malignant syndrome, malignant melanoma (see Contraindications).
Drug Interactions
Caution should be exercised when the following drugs are administered concomitantly with Sinemet:
Symptomatic postural hypotension can occur when Sinemet is added to the treatment of patients receiving antihypertensive drugs. Therefore, when therapy with Sinemet is started, dosage adjustment of the antihypertensive drug may be required. (For patients receiving MAOIs, see Contraindications.)
There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and Sinemet.
Phenothiazines and butyrophenones may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with Sinemet should be carefully observed for loss of therapeutic response.
Since levodopa competes with certain amino acids, the absorption of levodopa may be impaired in some patients on a high-protein diet. Co-administration with milk will significantly reduce levodopa level.
ATC Classification
N04BA02 - levodopa and decarboxylase inhibitor ; Belongs to the class of dopa and dopa derivative dopaminergic agents. Used in the management of Parkinson's disease.
Presentation/Packing
Sinemet 25/100: Tab 10 x 10's, 100's.
Sinemet 25/250: Tab 10 x 10's, 100's, 500's.
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