Syndopa CR 100 mg+25 mg

INDICATIONS

Idiopathic Parkinson's disease, in particular to reduce off-period in patients who previously have been treated with levodopa/decarboxylase inhibitors, or with levodopa alone and who have experienced motor fluctuations.

DOSAGE

Patients currently treated with conventional levodopa/decarboxylase inhibitor combinations: Dosage with Levodopa-Carbidopa prolonged-release tablet 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. A guide for substitution of Levodopa Carbidopa prolonged-release tablet treatment for conventional levodopa/decarboxylase inhibitor combinations is shown in the table below:Guideline for conversion from conventional Levodopa/Carbidopa tablet to Levodopa-Carbidopa prolonged-release tablet:



ConventionalLevodopa+Carbidopa Tablet
prolonged-release Levodopa+Carbidopa tablet
 


Daily Dosage (Levodopa)
Daily Dosage (Levodopa)
Dosage Regimen


300-400 mg
400 mg
1 tablet 2x daily


500-600 mg
600 mg
1 tablet 3x daily


700-800 mg
800 mg
4 tablets in 3 or 4 divided doses


900-1000
1000
5 tablets in 3 or more divided doses


1100-1200
1200
6 tablets in 3 or more divided doses


1300-1400
1400
7 tablets in 3 or more divided doses


1500-1600
1600
8 tablets in 3 or more divided doses

INTERACTION

Caution should be exercised when the following drugs are administered concomitantly with Levodopa-Carbidopa prolonged-release tablet. Antihypertensive agents: Symptomatic postural hypotension has occurred when levodopa/decarboxylase inhibitor combinations were added to the treatment of patients receiving some antihypertensive drugs. Therefore when therapy with Levodopa-Carbidopa prolonged-release tablet is started, dosage adjustment of the antihypertensive drug may be required. Antidepressants: There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa-levodopa preparations. Anticholinergics: Anticholinergics may affect the absorption and thus the patient’s response. Iron: Studies demonstrate a decrease in the bioavailability of carbidopa and/or levodopa when it is ingested with ferrous sulphate or ferrous gluconate. Other 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 Levodopa-Carbidopa prolonged-release tablet should be observed carefully for loss of therapeutic response. Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone. Since levodopa competes with certain amino acids, the absorption of levodopa may be impaired in some patients on a high protein diet. The effect of simultaneous administration of antacids with Levodopa-Carbidopa prolonged-release tablet on the bioavailability of levodopa has not been studied.

SIDE EFFECTS

The side-effect reported most frequently was dyskinesia (a form of abnormal involuntary movements). A greater incidence of dyskinesias was seen with Levodopa-Carbidopa prolonged-release tablet than with Levodopa-Carbidopa tablet. Other side-effects: nausea, hallucinations, confusion, dizziness, chorea, dry mouth, dream abnormalities, dystonia, insomnia, depression, asthenia, vomiting, anorexia, chest pain, palpitation, constipation, diarrhoea, dyspepsia, gastro-intestinal pain, dark saliva, angioedema, urticaria, pruritus, weight loss, neuroleptic malignant syndrome, agitation, anxiety, decreased mental acuity, paraesthesia, disorientation, fatigue, headache, extrapyramidal and movement disorders, falling, gait abnormalities, muscle cramps, on-off phenomenon, increased libido, psychotic episodes, dyspnoea, flushing, alopecia, rash, dark sweat, blurred vision, dark urine, cardiac irregularities, hypertension, phlebitis, bitter taste, sialorrhoea, dysphagia, bruxism, hiccups, gastro-intestinal bleeding, flatulence, burning sensation of tongue, development of duodenal ulcer, leucopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis.

PREGNANCY & 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. Levodopa-Carbidopa prolonged-release tablet should not be given during pregnancy and to nursing mothers.

PRECAUTIONS & WARNINGS

When patients are receiving levodopa monotherapy, levodopa must be discontinued at least eight hours before therapy with Levodopa-Carbidopa prolonged-release tablet is started (at least 12 hours if slow-release 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. Levodopa-Carbidopa prolonged-release tablet 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 Levodopa-Carbidopa prolonged-release tablet the onset of effect in patients with early morning dyskinesias may be slower than with conventional Levodopa-Carbidopa tablet. The incidence of dyskinesias is slightly higher during treatment with Levodopa-Carbidopa prolonged-release tablet than with conventional Levodopa-Carbidopa tablet (16.5% vs 12.2%) in advanced patients with motor fluctuations. Levodopa-Carbidopa prolonged-release tablet 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 Levodopa-Carbidopa prolonged-release tablet 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, Levodopa-Carbidopa prolonged-release tablet 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 Levodopa-Carbidopa prolonged-release tablet is substituted. These reactions are thought to be due to increased brain dopamine following administration of levodopa and use of Levodopa-Carbidopa prolonged-release tablet 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 Levodopa-Carbidopa tablet. Review of treatment is recommended if such symptoms develop.

USE IN SPECIAL POPULATIONS

Use in Children: Safety and effectiveness of Levodopa-Carbidopa prolonged-release tablet in infants and children have not been established, and its use in patients below the age of 18 is not recommended.

THERAPEUTIC CLASS

Antiparkinson drugs

STORAGE CONDITIONS

Store in a cool and dry place, protected from light.