TASMAR Film-coated tablet Ref.[9760] Active ingredients: Tolcapone

Posology

Paediatric population

Tasmar is not recommended for use in children below the age of 18 due to insufficient data on safety or efficacy. There is no relevant indication for use in children and adolescents.

Elderly patients

No dose adjustment of Tasmar is recommended for elderly patients.

Patients with hepatic impairment (see section 4.3)

Tasmar is contraindicated for patients with liver disease or increased liver enzymes.

Patients with renal impairment (see section 5.2)

No dose adjustment of Tasmar is recommended for patients with mild or moderate renal impairment (creatinine clearance of 30 ml/min or greater). Patients with severe renal impairment (creatinine clearance <30 ml/min) should be treated with caution. No information on the tolerability of tolcapone in these populations is available (see section 5.2).

Method of administration

The administration of Tasmar is restricted to prescription and supervision by physicians experienced in the management of advanced Parkinson’s disease.

Tasmar is administered orally three times daily. Tasmar may be taken with or without food (see section 5.2).

Tasmar tablets are film-coated and should be swallowed whole because tolcapone has a bitter taste.

Tasmar can be combined with all pharmaceutical formulations of levodopa/benserazide and levodopa/carbidopa (see also section 4.5).

The first dose of the day of Tasmar should be taken together the first dose of the day of a levodopa preparation, and the subsequent doses should be given approximately 6 and 12 hours later. Tasmar may be taken with or without food (see section 5.2).

The recommended dose of Tasmar is 100 mg three times daily, always as an adjunct to levodopa/benserazide or levodopa/carbidopa therapy. Only in exceptional circumstances, when the anticipated incremental clinical benefit justifies the increased risk of hepatic reactions, should the dose be increased to 200 mg three times daily (see sections 4.4 and 4.8). If substantial clinical benefits are not seen within 3 weeks of the initiation of the treatment (regardless of dose) Tasmar should be discontinued.

The maximum therapeutic dose of 200 mg three times daily should not be exceeded, as there is no evidence of additional efficacy at higher doses.

Liver function should be checked before starting treatment with Tasmar and then monitored every 2 weeks for the first year of therapy, every 4 weeks for the next 6 months and every 8 weeks thereafter. If the dose is increased to 200 mg tid, liver enzyme monitoring should take place before increasing the dose and then be reinitiated following the same sequence of frequencies as above (see sections 4.4 and 4.8).

Tasmar treatment should also be discontinued if ALT (alanine amino transferase) and/or AST (aspartate amino transferase) exceed the upper limit of normal or symptoms or signs suggest the onset of hepatic failure (see section 4.4).

Levodopa adjustments during Tasmar treatment

As Tasmar decreases the breakdown of levodopa in the body, side effects due to increased levodopa concentrations may occur when beginning Tasmar treatment. In clinical trials, more than 70% of patients required a decrease in their daily levodopa dose if their daily dose of levodopa was >600 mg or if patients had moderate or severe dyskinesias before beginning treatment.

The average reduction in daily levodopa dose was about 30% in those patients requiring a levodopa dose reduction. When beginning Tasmar, all patients should be informed of the symptoms of excessive levodopa dose and what to do if it occurs.

Levodopa adjustments when Tasmar is discontinued

The following suggestions are based on pharmacological considerations and have not been evaluated in clinical trials. Levodopa dose should not be decreased when Tasmar therapy is being discontinued due to side effects related to too much levodopa. However, when Tasmar therapy is being discontinued for reasons other than too much levodopa, levodopa dosemay have to be increased to levels equal to or greater than before initiation of Tasmar therapy, especially if the patient had large decreases in levodopa when starting Tasmar. In all cases, patients should be educated on the symptoms of levodopa under-dose and what to do if it occurs. Adjustments in levodopa are most likely to be required within 1-2 days of Tasmar discontinuation.

Isolated cases of either accidental or intentional overdose with tolcapone tablets have been reported. However clinical circumstances of these cases were so diverse, that no general conclusions can be drawn from the cases.

The highest dose of tolcapone administered to humans was 800 mg three times daily, with and without levodopa coadministration, in a one week study in healthy elderly volunteers. The peak plasma concentrations of tolcapone at this dose were on average 30 µg/ml (compared to 3 and 6 µg/ml with 100 mg tid and 200 mg tid of tolcapone respectively). Nausea, vomiting and dizziness were observed, particularly in combination with levodopa.

Management of overdose

Hospitalisation is advised. General supportive care is indicated. Based on the physicochemical properties of the compound, hemodialysis is unlikely to be of benefit.

5 years.

This medicinal product does not require any special storage conditions.

Tasmar is available in PVC/PE/PVDC blisters (pack sizes of 30 and 60 film-coated tablets) and in amber glass bottles without desiccant (pack sizes of 30, 60,100 and 200 film-coated tablets).

Not all pack sizes may be marketed.

No special requirements for disposal.