Presentation and Status in Health Basket
‘Sinemet CR’ tablets contain a 1:4 ratio of carbidopa to levodopa (‘Sinemet CR’: carbidopa 50 mg/levodopa 200 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. Route of administration: oral ‘Sinemet CR’ may be administered as whole or broken in half. So that the controlled release properties of the product 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 Dose Patients currently treated with conventional levodopa/decarboxylase inhibitor combinations Dosage with ‘Sinemet CR’ should be substituted initially at an amount that provides no more than approximately 10% more levodopa per day when higher dosages are given (more than 900 mg per day). The dosing interval between doses should be prolonged by 30 to 50% at intervals ranging from 4 to 12 hours. It is recommended to give the smaller dose, if divided doses are not equal, at the end of the day. The dose needs to be titrated further depending on clinical response, as indicated below under ‘Titration’. Dosages that provide up to 30% more levodopa per day may be necessary.
For full details see prescribing information.
Idiopathic Parkinson’s disease. Postencephalitic parkinsonism. Symptomatic parkinsonism (carbon monoxide or manganese intoxication). To reduce “off” time in patients previously treated with levodopa/decarboxylase inhibitor preparations, or with levodopa alone, who have had motor fluctuations characterized by end-of-dose deterioration (“wearing-off” phenomenon), peak dose dyskinesias, akinesia, or similar evidence of short-duration motor disturbances.
‘Sinemet CR’ should not be given when administration of a sympathomimetic amine is contraindicated. Non-selective monoamine oxidase (MAO) inhibitors are contraindicated for use with ‘Sinemet CR’. These inhibitors must be discontinued at least two weeks prior to initiating therapy with ‘Sinemet CR’. ‘Sinemet CR’ may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g. selegiline hydrochloride). ‘Sinemet CR’ is contraindicated in patients with known hypersensitivity to any component of this medication, and in patients with narrow-angle glaucoma. Because levodopa may activate a malignant melanoma, ‘Sinemet CR’ should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma. Use in patients with severe psychoses.
When patients are receiving levodopa monotherapy, levodopa must be discontinued at least eight hours before therapy with ‘Sinemet CR’ is started (at least 12 hours if slowrelease levodopa has been administered). Dyskinesias may occur in patients previously treated with levodopa alone because carbidopa permits more levodopa to reach the brain and, thus, more dopamine to be formed. The occurrence of dyskinesias may require dosage reduction. ‘Sinemet CR’ is not recommended for the treatment of drug-induced extrapyramidal reactions or for the treatment of Huntingdon’s chorea. Based on the pharmacokinetic profile of ‘Sinemet CR’ the onset of effect in patients with early morning dyskinesias may be slower than with conventional ‘Sinemet’. 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. ‘Sinemet CR’ should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or with a history of peptic ulcer disease or of convulsions. Care should be exercised in administering ‘Sinemet CR’ to patients with a history of recent myocardial infarction who have residual atrial, nodal, or ventricular arrhythmia. In such patients, cardiac function should be monitored with particular care during the period of initial dosage administration and titration. Levodopa has been associated with somnolence and episodes of sudden sleep onset. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with levodopa. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a reduction of dosage or termination of therapy may be considered. As with levodopa, ‘Sinemet CR’ may cause involuntary movements and mental disturbances. Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone or levodopa/decarboxylase inhibitor combination should be observed carefully when ‘Sinemet CR’ is substituted. These reactions are thought to be due to increased brain dopamine following administration of levodopa and use of ‘Sinemet CR’ may cause recurrence. Dosage reduction may be required. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution.
Impulse control disorders: Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Sinemet CR. Review of treatment is recommended if such symptoms develop. 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 carbidopa-levodopa combinations is reduced abruptly or discontinued, especially if the patient is receiving antipsychotics. Patients with chronic wide-angle glaucoma may be treated cautiously with ‘Sinemet CR’, provided the intraocular pressure is well controlled and the patient monitored carefully for changes in intraocular pressure during therapy. Periodic evaluations of hepatic, haematopoietic, cardiovascular and renal function are recommended during extended therapy. If general anaesthesia 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 medicine. Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk of developing melanoma than the general population (approximately 2-6 fold higher). It is unclear whether the increased risk observed was due to Parkinson’s disease, or other factors such as drugs used to treat Parkinson’s disease. Therefore patients and providers are advised to monitor for melanomas on a regular basis when using ‘Sinemet CR’ for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
For full details see prescribing information.
Choreiform, dystonic, and other involuntary movements. Mental changes, including paranoid ideation and psychotic episodes, depression with or without development of suicidal tendencies, and dementia. Convulsions have also occurred. Nausea. Rarely, gastrointestinal bleeding, development of duodenal ulcer, hypertension, phlebitis, hemolytic and non-hemolytic anemia, thrombocytopenia, leukopenia and agranulocytosis have occurred. Ataxia, numbness, confusion, sleepiness, insomnia, nightmares, hallucinations, delusions, agitation, anxiety, euphoria, dry mouth, bitter taste, sialorrhea, dysphagia, bruxism, hiccups, abdominal pain and distress, constipation, diarrhea, flatulence, burning sensation of tongue, weight gain or loss, edema, urinary retention, urinary incontinence, dark urine, priapism, diplopia, blurred vision, dilated pupils, oculogyric crises, weakness, faintness, fatigue, headache, hoarseness, malaise, hot flushes, sense of stimulation, bizarre breathing patterns, neuroleptic malignant syndrome.
Baclofen, benzodiazepines, clomidine, ferrous sulphate, methyldopa. MAOIs, antihypertensives, reserpine, phenothiazines, thioxanthines, butyrophenones, pimozide, sulpiride. Pyridoxine, amantadine, metoclopramide, domperidone, iron, halothane.
For full details see prescribing information.
Pregnancy and Lactation
There are insufficient data to evaluate the possible harmfulness of this substance when used in human pregnancy. It is not known whether carbidopa is excreted in human milk. In a study of one nursing mother with Parkinson’s disease, excretion of levodopa in breast milk was reported. ‘Sinemet CR’ should not be given during pregnancy and to nursing mothers.
Management of acute overdose with ‘Sinemet CR’ is basically the same as management of acute overdose with levodopa; however, pyridoxine is not effective in reversing the actions of ‘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. The possibility that the patient may have taken other drugs as well as ‘Sinemet CR’ should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdose is not known.