CO-CARELDOPA

The optimum daily dosage of Co-Careldopa must be determined by careful titration in each patient. Co-Careldopa 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 Co-Careldopa is being administered, although their dosage may have to be adjusted. Because both therapeutic and adverse effects are seen more rapidly with carbidopa/levodopa 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. Posology Patients not receiving levodopa If Co-Careldopa 25 mg/250 mg tablets are used, the initial dose is one-half tablet taken once or twice daily.

However, this may not provide the optimal amount of carbidopa needed by many patients. If necessary, add one-half tablet every day or every other day until optimal response 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. Patients receiving levodopa Discontinue levodopa at least 12 hours (24 hours for slow-release preparations) before starting therapy with Co-Careldopa.

The easiest way to do this is to give Co-Careldopa as the first morning dose after a night without any levodopa. The dose of Co-Careldopa 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 100 mg levodopa and 25 mg carbidopa three to 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 25 mg carbidopa and 250 mg levodopa and three or four times a day. Maintenance Therapy with Co-Careldopa should be individualised and adjusted gradually according to response.

When a greater proportion of carbidopa is required, each tablet of Co-Careldopa 100 mg/10 mg may be replaced with a tablet of Co-Careldopa 100 mg/25 mg. When more levodopa is required, 25 mg carbidopa and 250 mg levodopa and should be given three or four times a day.

Summary of the safety profile Side effects that occur frequently with levodopa/carbidopa are those due to the central neuropharmacological activity of dopamine. These reactions can usually be diminished by dosage reduction. The most common are dyskinesia including choreiform, dystonic and other involuntary movements and nausea.

Muscle twitching and blepharospasm may be taken as early signs to consider dosage reduction. Tabulated list of adverse reactions Adverse reactions from clinical trials and post-marketing experience are per System Organ Class and per frequency.

4) Musculoskeletal, connective tissues, and bone disorders Uncommon Muscle cramp Not known Muscle twitching Renal and urinary disorders Uncommon Dark urine Rare Urinary retention, urinary incontinence Reproductive system and breast disorders Rare Priapism General disorders and administration site conditions Common Fatigue, faintness Uncommon Chest pain, asthenia, malaise, hot flushes, weakness 1 Rarely convulsions have occurred; however, a causal relationship with levodopa/carbidopa has not been established.

4). Dopamine Dysregulation Syndrome (DDS) Dopamine Dysregulation Syndrome (DDS) is an addictive disorder seen in some patients treated with levodopa/carbidopa. 4). 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. uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store.

Co-Careldopa can be administered to patients already receiving levodopa alone. However, the treatment with levodopa alone should be discontinued at least 12 hours (24 hours for slow-release preparations) prior to start of treatment with Co-Careldopa.

2). 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 or combination of levodopa and a decarboxylase inhibitor should be observed carefully when Co-Careldopa is substituted.

These reactions are thought to be due to increased brain dopamine following administration of levodopa, and use of Co-Careldopa may cause a recurrence. A reduction of dosage may be required. 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. Levodopa/carbidopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of convulsions or peptic ulcer disease (because of the possibility of upper gastrointestinal haemorrhage).

Care should be exercised when levodopa/carbidopa 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 and dosage adjustments.

As with levodopa, periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function are recommended during extended therapy. Levodopa/carbidopa is not recommended in the treatment of drug-induced extrapyramidal reactions and in the treatment of Huntington’s chorea.

1. • Levodopa/carbidopa should not be given when administration of a sympathomimetic compound is contraindicated. • Non-selective monoamine oxidase (MAO) inhibitors and selective MAO-type- A inhibitors. g. 5). • Narrow-angle glaucoma. • Malignant melanoma.

Since levodopa may activate a malignant melanoma, it should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.