TASMAR

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 No dose adjustment of Tasmar is recommended for elderly patients.

3) Tasmar is contraindicated for patients with liver disease or increased liver enzymes. 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. 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. 2). Tasmar tablets are film-coated and should be swallowed whole because tolcapone has a bitter taste. 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.

2). The recommended dose of Tasmar is 100 mg three times daily, always as an adjunct to levodopa/benserazide or levodopa/carbidopa therapy. 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.

8). 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.

The most commonly observed adverse reactions associated with the use of Tasmar, occurring more frequently than in placebo-treated patients are listed in the table below. However, Tasmar, as a COMT inhibitor, is known to increase the bioavailability of the co-administered levodopa.

The consequent increase in dopaminergic stimulation can lead to the dopaminergic side effects observed after treatment with COMT inhibitors. The most common of these are increased dyskinesia, nausea, vomiting, abdominal pain, syncope, orthostatic complains, constipation, sleep disorders, somnolence, hallucination.

4). 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 (frequency cannot be estimated from the available data) Experience with Tasmar obtained in parallel placebo-controlled randomised studies in patients with Parkinson’s disease is shown in the following table, which lists adverse reactions with a potential relationship to Tasmar.

e. where a specific adverse reaction was not observed in clinical trials but was reported post-marketing only) are indicated by an asterisk (*), and the frequency category has been calculated according to EU Guideline. Increase of alanine aminotransferase Increases to more than three times the upper limit of normal (ULN) in alanine aminotransferase (ALT) occurred in 1 % of patients receiving Tasmar 100 mg three times daily, and 3 % of patients at 200 mg three times daily.

Increases were approximately two times more likely in females. The increases usually appeared within 6 to 12 weeks of starting treatment, and were not associated with any clinical signs or symptoms. In about half the cases, transaminase levels returned spontaneously to baseline values whilst patients continued Tasmar treatment.

For the remainder, when treatment was discontinued, transaminase levels returned to pre- treatment levels. 4). 4) have been reported following reduction or discontinuation of Tasmar and following introduction of Tasmar when this was accompanied by a significant reduction in other concomitant dopaminergic medications.

Tasmar therapy should only be initiated by physicians experienced in the management of advanced Parkinson’s disease, to ensure an appropriate risk-benefit assessment. Tasmar should not be prescribed until there has been a complete informative discussion of the risks with the patient.

Tasmar should be discontinued if substantial clinical benefits are not seen within 3 weeks of the initiation of the treatment regardless of dose. Liver injury Because of the risk of rare but potentially fatal acute liver injury, Tasmar is only indicated for use in patients with levodopa-responsive idiopathic Parkinson’s disease and motor fluctuations, who failed to respond to or are intolerant of other COMT inhibitors.

Periodic monitoring of liver enzymes cannot reliably predict the occurrence of fulminant hepatitis. However, it is generally believed that early detection of medicine-induced hepatic injury along with immediate withdrawal of the suspect medication enhances the likelihood for recovery.

Liver injury has most often occurred between 1 month and 6 months after starting treatment with Tasmar. Additionally late onset hepatitis after approximately 18 months of treatment has been reported rarely. 8).

Before starting treatment:

If liver function tests are abnormal or there are signs of impaired liver function, Tasmar should not be prescribed. If Tasmar is to be prescribed, the patient should be informed about the signs and symptoms which may indicate liver injury, and to contact the physician immediately.

During treatment:

Liver function should be 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 re-initiated following the sequence of frequencies as above.

1. • Evidence of liver disease or increased liver enzymes. • Severe dyskinesia. • A previous history of Neuroleptic Malignant Syndrome (NMS) Symptom Complex and/or non- traumatic rhabdomyolysis or hyperthermia. • Phaeochromocytoma. • Treatment with non-selective mono amino oxidase (MAO) inhibitors.