CO-CARELDOPA

Posology The optimum daily dosage of carbidopa/levodopa must be determined by careful titration in each patient. Co-Careldopa 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.

For doses not attainable with this medicine, other medicines and strengths are available. 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 carbidopa/levodopa is being administered, although their dosage may have to be adjusted.

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. Dosage may be best initiated with one tablet of Co-Careldopa 25 mg/100 mg three times a day.

This dosage schedule provides 75 mg of carbidopa per day. 5 mg/50 mg or Co-Careldopa 25 mg/100 mg every day or every other day, as necessary, until a dosage equivalent of eight tablets of Co-Careldopa 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 Co-Careldopa 10 mg/100 mg tablets may be used to facilitate dosage titration according to the needs of the individual patient. Maintenance Therapy with Co-Careldopa should be individualised and adjusted gradually according to response.

5 mg/50 mg. When more levodopa is required, Co-Careldopa 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 Co-Careldopa 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 inhibitor Begin with a dosage of Co-Careldopa that will provide the same amount of levodopa as contained in the other levodopa/decarboxylase inhibitor combination.

Summary of the safety profile Side effects that occur frequently with carbidopa/levodopa 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. 4). Tabulated list of adverse reactions MedDRA System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (>1/1,000 to <1/100) Rare (>1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) Blood and lymphatic system disorders Leukopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia Agranulocytosis Metabolism and nutrition disorders Anorexia Weight gain or loss Psychiatric Hallucinations, Agitation, fear, Dopamine disorders confusion, reduced thinking dysregulation dizziness, capacity, syndrome nightmares, disorientation, sleepiness, headache, increased fatigue, libido, numbness insomnia, and convulsions, depression with psychotic episodes very rare suicide including delusions attempts, and paranoid euphoria, ideation dementia, feeling of stimulation, dream abnormalities Nervous system Dyskinesia, Ataxia, Malignant Levodopa/carbi Muscle disorders chorea, increased hand neuroleptic dopa is twitching dystonia, tremor syndrome, associated with extrapyramidal paraesthesia, somnolence and and movement falling, walking has been disorders, defects, trismus associated very bradykinetic rarely with episodes (the excessive “on-off” daytime phenomenon) somnolence and may appear sudden sleep some months to onset episodes.

years after the beginning of treatment with levodopa and is probably related to the progression of the disease. The adaptation of dose schedule and dose intervals may be required Eye disorders Blurred vision, blepharospasm, activation of a latent Horner's syndrome, diplopia, dilated pupils, and oculogyric crises.

Co-Careldopa is not recommended for the treatment of drug-induced extrapyramidal reactions. Co-Careldopa 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 Co-Careldopa 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.

Co-Careldopa may induce orthostatic hypotension. Therefore Co-Careldopa should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension. 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, Co-Careldopa 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 Co- Careldopa is substituted.

1. Non-selective monoamine oxidase (MAO) inhibitors and selective MAO type A inhibitors are contraindicated for use with Co-Careldopa. These inhibitors must be discontinued at least two weeks before starting therapy with Co-Careldopa.

g. 5). Co-Careldopa 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. g. pheochromocytoma, hyperthyroidism, Cushing's syndrome, severe cardiovascular diseases.