LECADO

Posology The daily dose of levodopa/carbidopa should be carefully determined. Patients should be monitored closely during the period of dose adjustment, especially with regard to the occurrence or exacerbation of nausea and abnormal involuntary movements, such as dyskinesia, chorea and dystonia.

Blepharospasm could be an early sign of overdosing. • Starting dose Patients who have never before received Levodopa therapy Lecado 100/25 mg is designed for use in patients, who have not previously had levodopa treatment or to aid titration in patients who receive Lecado 200/50 mg.

The recommended starting dose is one tablet of Lecado 100/25 mg two times per day. In patients who need more levodopa a daily dose of three to four tablets of Lecado 100/25 mg is usually well tolerated. For Lecado 200/50 mg the recommended starting dose is one tablet two times per day.

The starting dose should not be higher than 600 mg levodopa per day and the doses should be administered with minimum intervals of six hours. Dose adjustments should occur with intervals of at least two to four days. Depending of the severity of the disease, six months of treatment may be required to achieve optimal disease control.

A guide to substitution for patients who are treated with the immediate-release combination of levodopa and decarboxylase inhibitor Transferring to Lecado 100/25 mg should initially occur in a dose that supplies at most about 10% more levodopa per day when higher doses are indicated (more than 900 mg daily).

Levodopa and decarboxylase inhibitor should be discontinued at least 12 hours before the administration of Lecado. The dose interval should be prolonged by 30 % to 50% at intervals of ranging from 4 – 12 hours. If the divided doses are not equal it is recommended to administer the lowest dose at the end of the day.

The dose should be adjusted depending on the clinical reaction, as indicated below in Dose Adjustment. It could be that doses which supply maximally 30% more levodopa per day are necessary. A guide for the substitution of Lecado prolonged-release treatment for immediate-release levodopa/carbidopa combinations is shown in the table below: Levodopa/carbidopa Lecado 100/25 mg Daily dose Levodopa (mg) Daily dose Levodopa (mg) Dose schedule 100-200 200 1 tablet, twice daily 300-400 400 4 tablets divided in 3 or more doses For higher doses Lecado200/50 mg is available.

Side effects that occur frequently in patients receiving levodopa/carbidopa are those due to the central neuropharmacologic activity of dopamine. These reactions usually can be diminished by dose reduction. The most common side effects are dyskinesias, including choreiform, dystonic, and other involuntary movements and nausea.

Muscle twitching and blepharospasm may be taken as early signs to consider dose reduction. During controlled clinical studies in patients with moderate to severe motor fluctuations Lecado caused no side effects which were unique to the modified release formulation.

4).

Psychiatric disorders: dementia Dopamine dysregulation syndrome:

Dopamine Dysregulation Syndrome (DDS) is an addictive disorder seen in some patients treated with carbidopa/ levodopa. 4).

Nervous system disorders Common (≥ 1/100 to < 1/10):

Dyskinesia (a higher frequency of dyskinesia was seen with Lecado than with the immediate-release formulation of Levodopa/Carbidopa), chorea, dystonia, extrapyramidal and movement disorders, the “on-off”-appearance Bradykinesia (on-off episodes) may appear some months to 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. ), paraesthesia, falling, walking defects, trismus Levodopa/carbidopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

Eye disorders Rare (≥ 1/10,000 to < 1/1,000):

Hazy vision, blepharospasm, activation of a latent Horner’s syndrome, double vision, dilated pupils and oculogyric crises Blepharospasm can be an early sign of overdosage. 3) Musculoskeletal, connective tissue and bone disorders Uncommon (≥ 1/1,000 to < 1/100): Muscle spasms Renal and urinary disorders Uncommon (≥ 1/1,000 to < 1/100): Dark urine Rare (≥ 1/10,000 to < 1/1,000): Urinary retention, urinary incontinence, priapism General disorders and administration site conditions Uncommon (≥ 1/1,000 to < 1/100): Weakness, malaise, flare ups Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

In patients who are treated with just levodopa, treatment should have been discontinued for at 12 hours before starting with the therapy of Lecado. Based on the pharmacokinetic profile of Lecado the onset of effect in patients with early morning dyskinesia may be slower than with immediate-release levodopa/ carbidopa.

2%). Dyskinesia can occur in patients who previously were treated with just levodopa, because carbidopa makes it possible for more levodopa to reach the brain, which causes more dopamine to be formed. 8). Lecado is not recommended for the treatment of drug-induced extrapyramidal reactions or for the treatment of Huntingdon’s chorea.

Lecado 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, haematemesis or of convulsions. Care should be exercised in administering Lecado to patients with a history of 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 or an episode of sudden sleep onset must refrain from driving or operating machines.

A reduction of dosage or termination of therapy may be considered. Lecado can, just like levodopa, cause involuntary movements and mental disturbances. Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone or with carbidopa- levodopa combination should be observed carefully when Lecado is substituted.

Lecado should not be given when administration of a sympathomimetic amine is contraindicated. Non-selective mono-amino-oxydase (MAO) inhibitors and selective MAO type A inhibitors are contraindicated for concomitant use with Lecado.

The administration of these inhibitors should be discontinued at least two weeks before starting the treatment with Lecado. 5). Lecado is contraindicated in: - patients with a hypersensitivity to levodopa, carbidopa or any of the excipients - patients with narrow-angle glaucoma - patients with severe heart failure - severe cardiac arrhythmia - acute stroke - patients with severe phychoses.

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