SINEMET

Posology The optimum daily dosage of 'Sinemet' must be determined by careful titration in each patient. 'Sinemet' Tablets are available in a ratio of 1:4 or 1:10 of carbidopa to levodopa to provide facility for fine dosage titration for each patient.

General Considerations Studies 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 levodopa Dosage 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. 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.

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. ) 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. 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 levodopa Discontinue 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. Maintenance Therapy with 'Sinemet' should be individualised and adjusted gradually according to response.

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.

Side effects that occur frequently with 'Sinemet' are those due to the central neuropharmacological activity of dopamine. These reactions can usually be diminished by dosage reduction. The most common are dyskinesias including choreiform, dystonic and other involuntary movements and nausea.

Muscle twitching and blepharospasm may be taken as early signs to consider dosage reduction. Other side effects reported in clinical trials or in post-marketing experience include: Infections and infestations: urinary tract infections (frequency: very common) Body as a whole: syncope, chest pain, anorexia.

Cardiovascular: cardiac irregularities and/or palpitations, orthostatic effects including hypotensive episodes, hypertension, phlebitis. Gastro-intestinal: vomiting, gastro-intestinal bleeding, development of duodenal ulcer, diarrhoea, dark saliva.

Haemotologic: leucopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis. Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Schonlein purpura. 3 ‘Contraindications’), bradykinetic episodes (the “on-off” phenomenon), dizziness, paraesthesia, psychotic episodes including delusions, hallucinations and paranoid ideation, depression with or without development of suicidal tendencies, dementia, dream abnormalities, agitation, confusion, increased libido.

Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes. Respiratory: dyspnoea. Skin: alopecia, rash, dark sweat. Urogenital: dark urine. Rarely convulsions have occurred; however, a causal relationship with 'Sinemet' has not been established.

Other side effects that have been reported with levodopa or levodopa/carbidopa combinations and may be potential side effects with 'Sinemet' include: Gastro-intestinal: dyspepsia, dry mouth, bitter taste, sialorrhoea, dysphagia, bruxism, hiccups, abdominal pain and distress, constipation, flatulence, burning sensation of the tongue.

'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, or history of peptic ulcer disease (because of the possibility of upper gastro-intestinal haemorrhage).

Care should be exercised when 'Sinemet' is administered to patients with a history of myocardial infarction who have residual atrial nodal, or ventricular arrhythmias. Cardiac function should be monitored with particular care in such patients during the period of initial dosage adjustment.

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. All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious antisocial behaviour.

Patients with current psychoses should be treated with caution. 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. As with levodopa, 'Sinemet' may cause involuntary movements and mental disturbances. Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone should be observed carefully when 'Sinemet' is substituted.

Non-selective monoamine oxidase (MAO) inhibitors are contraindicated for use with 'Sinemet'. These inhibitors must be discontinued at least two weeks before starting 'Sinemet'. g. selegiline hydrochloride). 1. 'Sinemet' is contraindicated in patients with narrow-angle glaucoma.

Since levodopa may activate a malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma. Use in patients with severe psychoses. 6 ‘Fertility, pregnancy and lactation’.