COMTESS

Entacapone should only be used in combination with levodopa/benserazide or levodopa/carbidopa. The prescribing information for these levodopa preparations is applicable to their concomitant use with entacapone. Posology One 200 mg tablet is taken with each levodopa/dopa decarboxylase inhibitor dose.

e. 2,000 mg of entacapone. Entacapone enhances the effects of levodopa. g. dyskinesias, nausea, vomiting and hallucinations, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment.

The daily dose of levodopa should be reduced by about 10-30% by extending the dosing intervals and/or by reducing the amount of levodopa per dose, according to the clinical condition of the patient. If entacapone treatment is discontinued, it is necessary to adjust the dosing of other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of control of the parkinsonian symptoms.

Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide preparations slightly (5-10%) more than from standard levodopa/carbidopa preparations. Hence, patients who are taking standard levodopa/benserazide preparations may need a larger reduction of levodopa dose when entacapone is initiated.

Renal impairment Renal insufficiency does not affect the pharmacokinetics of entacapone and there is no need for dose adjustment. 2). Hepatic impairment See section

Summary of the safety profile The most frequent adverse reactions caused by entacapone relate to the increased dopaminergic activity and occur most commonly at the beginning of treatment. Reduction of levodopa dosage decreases the severity and frequency of these reactions.

The other major class of adverse reactions are gastrointestinal symptoms, including nausea, vomiting, abdominal pain, constipation and diarrhoea. Urine may be discoloured reddish-brown by entacapone, but this is a harmless phenomenon.

Usually the adverse reactions caused by entacapone are mild to moderate. g. g. 7%). 2%) were reported significantly more often with entacapone than with placebo in pooled data from clinical studies involving 406 patients taking the medicinal product and 296 patients taking placebo.

Some of the adverse reactions, such as dyskinesia, nausea, and abdominal pain, may be more common with the higher doses (1,400 to 2,000 mg per day) than with the lower doses of entacapone. Tabulated list of adverse reactions The following adverse reactions, listed below in Table 1, have been accumulated both from clinical studies with entacapone and since the introduction of entacapone into the market.

Table 1. g. ) Skin and subcutaneous tissue disorders Rare: Erythematous or maculopapular rash Very rare: Urticaria Not known: Skin, hair, beard and nail discolourations Renal and urinary disorders Very common: Urine discoloration General disorders and administration site conditions Common: Fatigue, sweating increased, fall Very rare: Weight decrease * Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: 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, since no valid estimate can be derived from clinical trials or epidemiological studies).

Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson’s disease. g. agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase.

In individual cases, only some of these symptoms and/or findings may be evident. Neither NMS nor rhabdomyolysis have been reported in association with entacapone treatment from controlled trials in which entacapone was discontinued abruptly.

Since the introduction into the market, isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other concomitant dopaminergic medicinal products. When considered necessary, withdrawal of entacapone and other dopaminergic treatment should proceed slowly, and if signs and/or symptoms occur despite a slow withdrawal of entacapone, an increase in levodopa dosage may be necessary.

Entacapone therapy should be administered cautiously to patients with ischaemic heart disease. Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal products containing a catechol group and potentiate their action.

g. 5). Entacapone is always given as an adjunct to levodopa treatment. Hence, the precautions valid for levodopa treatment should also be taken into account for entacapone treatment. Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide preparations 5-10% more than from standard levodopa/carbidopa preparations.

8). 8). Entacapone may aggravate levodopa-induced orthostatic hypotension. Entacapone should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension. g. dyskinesia, were more common in patients who received entacapone and dopamine agonists (such as bromocriptine), selegiline or amantadine compared to those who received placebo with this combination.

3. Elderly No dosage adjustment of entacapone is required for elderly. Paediatric population The safety and efficacy of Comtess in children below age 18 have not been established. No data are available. Method of administration Entacapone is administered orally and simultaneously with each levodopa/carbidopa or levodopa/benserazide dose.

2). 1. - Hepatic impairment. - Phaeochromocytoma. g. phenelzine, tranylcypromine). 5). - A previous history of neuroleptic malignant syndrome (NMS) and/or non- traumatic rhabdomyolysis.