- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- Legal category
General ConsiderationsStudies show that the peripheral dopa-decarboxylase is fully inhibited (saturated) by carbidopa at doses between 70 and 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.Standard antiparkinsonian drugs, other than levodopa alone, may be continued while 'Sinemet' is being administered, although their dosage may have to be adjusted.Because both therapeutic and adverse effects are seen more rapidly with 'Sinemet' than with levodopa, patients should be carefully monitored during the dosage adjustment period. Involuntary movements, particularly blepharospasm, are a useful early sign of excess dosage in some patients.
Patients not receiving levodopaDosage may be best initiated with one tablet of 'Sinemet Plus 25 mg/100 mg' three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet of 'Sinemet 12.5 mg/50 mg' or 'Sinemet Plus 25 mg/100 mg' every day or every other day, as necessary, until a dosage equivalent of eight tablets of 'Sinemet Plus 25 mg/100 mg' a day is reached.If 'Sinemet 10 mg/100 mg Tablets' or 'Sinemet 12.5 mg/50 mg Tablets' are used, dosage may be initiated with one tablet three or four times a day. Titration upward may be required in some patients to achieve optimum dosage of carbidopa. The dosage may be increased by one tablet every day or every other day until a total of eight tablets (two tablets q.d.s.) is reached. Response has been observed in one day, and sometimes after one dose. Fully effective doses usually are reached within seven days as compared to weeks or months with levodopa alone.'Sinemet 12.5 mg/50 mg Tablets' or 'Sinemet 10 mg/100 mg Tablets' may be used to facilitate dosage titration according to the needs of the individual patient.
Patients receiving levodopaDiscontinue levodopa at least 12 hours (24 hours for slow-release preparations) before starting therapy with 'Sinemet'. The easiest way to do this is to give 'Sinemet' as the first morning dose after a night without any levodopa. The dose of 'Sinemet' should be approximately 20% of the previous daily dosage of levodopa.Patients taking less than 1,500 mg levodopa a day should be started on one tablet of 'Sinemet Plus 25 mg/100 mg' three or four times a day dependent on patient need. The suggested starting dose for most patients taking more than 1,500 mg levodopa a day is one tablet of 'Sinemet 25 mg/250 mg' three or four times a day.
MaintenanceTherapy with 'Sinemet' should be individualised and adjusted gradually according to response. When a greater proportion of carbidopa is required, each tablet of 'Sinemet 10 mg/100 mg' may be replaced with a tablet of 'Sinemet Plus 25 mg/100 mg' or 'Sinemet 12.5 mg/50 mg'.When more levodopa is required, 'Sinemet 25 mg/250 mg Tablets' should be substituted at a dosage of one tablet three or four times a day. If necessary, the dosage of 'Sinemet 25 mg/250 mg Tablets' may be increased by one tablet every day or every other day to a maximum of eight tablets a day. Experience with a total daily dosage greater than 200 mg carbidopa is limited.
Patients receiving levodopa with another decarboxylase inhibitorWhen transferring a patient to 'Sinemet' from levodopa combined with another decarboxylase inhibitor, discontinue dosage at least 12 hours before 'Sinemet' is started. Begin with a dosage of 'Sinemet' that will provide the same amount of levodopa as contained in the other levodopa/decarboxylase inhibitor combination.
Patients receiving other antiparkinsonian agentsCurrent evidence indicates that other antiparkinsonian agents may be continued when 'Sinemet' is introduced, although dosage may have to be adjusted in line with manufacturers recommendations.
Use in childrenThe safety of 'Sinemet' in patients under 18 years of age has not been established and its use in patients below the age of 18 is not recommended.
Use in the elderlyThere is wide experience in the use of this product in elderly patients. The recommendations set out above reflect the clinical data derived from this experience.
Impulse control disordersPatients 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. Review of treatment is recommended if such symptoms develop. Concomitant administration of psycho-active drugs such as phenothiazines or butyrophenones should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect. Patients with a history of convulsions should be treated with caution.As with levodopa, periodic evaluation of hepatic, haematopoetic, cardiovascular and renal function are recommended during extended therapy.Patients with chronic wide-angle glaucoma may be treated cautiously with 'Sinemet', provided the intra-ocular pressure is well controlled and the patient monitored carefully for changes in intra-ocular pressure during therapy.If general anaesthesia is required, therapy with 'Sinemet' may be continued for as long as the patient is permitted to take fluids and medication by mouth. If therapy has to be stopped temporarily, 'Sinemet' may be restarted as soon as oral medication can be taken at the same daily dosage as before.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' for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Laboratory TestsCommonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of 'Sinemet' than with levodopa. Transient abnormalities include elevated levels of blood urea, AST (SGOT), ALT (SGPT), LDH, bilirubin, and alkaline phosphatase.Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.Positive Coombs' tests have been reported, both with 'Sinemet' and levodopa alone.'Sinemet' may cause a false positive result when a dipstick is used to test for urinary ketone; and this reaction is not altered by boiling the urine. The use of glucose oxidase methods may give false negative results for glycosuria.
Antihypertensive agentsPostural hypotension can occur when 'Sinemet' is added to the treatment of patients already receiving antihypertensive drugs. Dosage adjustment of the antihypertensive agent may be required.
AntidepressantsRarely, reactions including hypertension and dyskinesia have been reported with the concomitant use of tricyclic antidepressants. (See first paragraph of 4.3 'Contraindications' for patients receiving MAOIs).
AnticholinergicsAnticholinergics may affect the absorption and thus the patient's response.
IronStudies demonstrate a decrease in the bioavailability of carbidopa and/or levodopa when it is ingested with ferrous sulphate or ferrous gluconate.
Other drugsTo date there has been no indication of interactions that would preclude concurrent use of standard antiparkinsonian drugs.Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones, and risperidone) and isoniazid, may reduce the therapeutic effects of levodopa. 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. Use of 'Sinemet' 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 'Sinemet' may be impaired in some patients on a high protein diet.The effect of simultaneous administration of antacids with 'Sinemet' on the bioavailability of levodopa has not been studied.'Sinemet' may be given to patients with Parkinson's disease and syndrome who are taking vitamin preparations that contain pyridoxine hydrochloride (Vitamin B6).
PregnancyAlthough the effects of 'Sinemet' on human pregnancy are unknown, both levodopa and combinations of carbidopa and levodopa have caused visceral and skeletal malformations in rabbits. Therefore, the use of 'Sinemet' in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards should pregnancy occur.
Breast-feeding mothersIt 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 human breast milk was reported. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in infants, a decision should be made whether to discontinue breast-feeding or discontinue the use of 'Sinemet', taking into account the importance of the drug to the mother.
Impulse control disordersPathological 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 (see section 4.4. 'Special warnings and precautions for use') Skin: flushing, increased sweating.Special senses: diplopia, blurred vision, dilated pupils, oculogyric crises.Urogenital: urinary retention, urinary incontinence, priapism.Miscellaneous: weakness, faintness, fatigue, headache, hoarseness, malaise, hot flushes, sense of stimulation, bizarre breathing patterns, malignant melanoma (see 4.3 'Contraindications'). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at website www.mhra.gov.uk/yellowcard.
TreatmentManagement of acute overdosage with 'Sinemet' is basically the same as management of acute overdosage with levodopa; however pyridoxine is not effective in reversing the actions of 'Sinemet'. ECG monitoring should be instituted, and the patient carefully observed for the possible development of arrhythmias; if required, appropriate anti-arrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as 'Sinemet' should be taken into consideration. To date, no experience has been reported with dialysis, and hence its value in the treatment of overdosage is not known. The terminal half-life of levodopa is about two hours in the presence of carbidopa.
|Sinemet 12.5 mg/50 mg Tablets||PL 00025/0226|
|Sinemet 10 mg/100 mg Tablets||PL 00025/0084|
|Sinemet Plus 25 mg/100 mg Tablets||PL 00025/0150|
|Sinemet 25 mg/250 mg Tablets||PL 00025/0085|
|Sinemet 12.5 mg/50 mg Tablets||11 February 1988 / 16 April 2008|
|Sinemet 10 mg/100 mg Tablets||23 October 1973 / 16 April 2008|
|Sinemet Plus 25 mg/100 mg Tablets||11 June 1981 / 16 April 2008|
|Sinemet 25 mg/250 mg Tablets||23 October 1973 / 16 April 2008|
Merck Sharp & Dohme Limited
Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU
+44 (0)1992 479 292
Call MSD customer services on 01992 452094
+44 (0)1992 467 272