Special Warning : אזהרת שימוש

4.4        Special warnings and precautions for use
Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson’s disease. Isolated cases of rhabdomyolysis have been reported with entacapone treatment.
NMS, including rhabdomyolysis and hyperthermia, is characterized by motor symptoms (rigidity, myoclonus, tremor), mental status changes (e.g. agitation, confusion, coma), COM API FEB14 CL V8 COR CPO CL                                                   REF BPI 180613 hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase (CPK). In individual cases, only some of these symptoms and/or findings may be evident.
Isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other dopaminergic medications. 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 with caution 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. Thus, entacapone should be administered cautiously to patients being treated with medicinal products metabolized by catechol-O-methyl transferase (COMT), e.g. rimiterol, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, alpha-methyldopa, and apomorphine (see section 4.5 Interaction with other medicinal products and other forms of interaction).
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 to 10% more than from standard levodopa/carbidopa preparations.
Consequently, undesirable dopaminergic effects may be more frequent when entacapone is added to levodopa/benserazide treatment (see section 4.8 Undesirable effects). To reduce levodopa-related dopaminergic adverse reactions, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment, according to the clinical condition of the patient (see section 4.2 Posology and method of administration and 4.8 Undesirable effects).
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.
In clinical studies, undesirable dopaminergic effects, e.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. The doses of other antiparkinsonian medications may need to be adjusted when entacapone treatment is initiated.
Entacapone used in combination with levodopa has been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson’s disease and caution should therefore be exercised when driving or operating machines (see section 4.7 Effects on ability to drive and use machines).
For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease. Prolonged or persistent diarrhoea suspected to be related to entacapone may be a sign of colitis. In the event of prolonged or persistent diarrhoea, entacapone should be discontinued and appropriate medical therapy and investigations considered.
For patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time, a general medical evaluation including liver function should be considered.
COM API FEB14 CL V8 COR CPO CL                                                  REF BPI 180613 Patients should be regularly monitored for the development of impulse control disorders.
Patients and caregivers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments such as entacapone in association with levodopa. Review of treatment is recommended if such symptoms develop.
Comtan tablets contain sucrose. Therefore, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Effects on Driving

4.7       Effects on ability to drive and use machines
Comtan in association with levodopa may have major influence on the ability to drive and use machines. Patients being treated with entacapone in association with levodopa and presenting with somnolence and/or sudden sleep onset episodes must be instructed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such recurrent episodes have resolved (see section 4.4 Special warnings and precautions for use).
Entacapone may, together with levodopa, cause dizziness and symptomatic orthostatism.
Therefore, caution should be exercised when driving or using machines.