Summary of the safety profileThe most frequent adverse reactions caused by entacapone relate to the increased dopaminergic activity and occur most commonly at the beginning of the 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. In clinical studies the most common adverse reactions leading to discontinuation of entacapone treatment have been gastrointestinal symptoms (e.g. diarrhoea, 2.5%) and increased dopaminergic adverse reactions of levodopa (e.g. dyskinesias, 1.7%).Dyskinesias (27%), nausea (11%), diarrhoea (8%), abdominal pain (7%) and dry mouth (4.2%) 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 reactionsThe 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 . Adverse drug reactions *
* 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). ** The incidence rates of myocardial infarction and other ischemic heart disease events (0.43% and 1.54%, respectively) are derived from an analysis of 13 double-blind studies involving 2082 patients with end-of-dose motor fluctuations receiving entacapone.
|Common:||Insomnia, hallucinations, confusion, paroniria|
|Nervous system disorders|
||Parkinsonism aggravated, dizziness, dystonia, hyperkinesia
|Common:||Ischemic heart disease events other than myocardial infarction (e.g. angina pectoris)|
||Diarrhoea, abdominal pain, dry mouth, constipation, vomiting
|Rare:||Hepatic function tests abnormal|
||Hepatitis with mainly cholestatic features (see section 4.4.)
|Skin and subcutaneous tissue disorders|
|Rare:||Erythematous or maculopapular rash|
|Not known:||Skin, hair, beard and nail discolorations|
|Renal and urinary disorders|
|Very common:||Urine discoloration|
|General disorders and administration site conditions|
|Common:||Fatigue, sweating increased, fall|
Description of selected adverse reactionsEntacapone in association with levodopa has been associated with isolated cases of excessive daytime somnolence and sudden sleep onset episodes.Impulse control disorders: 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 Comtess in association with levodopa (see section 4.4).Isolated cases of NMS have been reported following abrupt reduction or discontinuation of entacapone and other dopaminergic treatments.Isolated cases of rhabdomyolysis have been reported.