Adverse reactions : תופעות לוואי

4.8       Undesirable effects
Very common undesirable effects found in double-blind placebo controlled phase III studies are dyskinesia, nausea, and abnormal urine (see below).
Common undesirable effects found in double-blind placebo controlled phase III studies are diarrhoea, Parkinsonism aggravated, dizziness, abdominal pain, insomnia, dry mouth, fatigue, hallucinations, constipation, dystonia, increased sweating, hyperkinesia, headache, leg cramps, confusion, paroniria, fall, postural hypotension, vertigo and tremor.
Most of the undesirable effects caused by entacapone relate to the increased dopaminergic activity and occur most commonly at the beginning of treatment. Reduction of levodopa dosage may decrease the severity and frequency of these effects. The other major class of undesirable effects are gastrointestinal symptoms, including e.g. nausea, vomiting, abdominal pains, constipation and diarrhoea. Urine may be discoloured reddish-brown by entacapone, but this is a harmless phenomenon.
Usually undesirable effects caused by entacapone are mild to moderate. The most common undesirable effects leading to discontinuation of entacapone treatment have been gastrointestinal symptoms (e.g. diarrhoea, 2.5%) and dopaminergic symptoms (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 clinical studies.
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.
Slight decreases in haemoglobin, erythrocyte count and haematocrit have been reported during entacapone treatment. The underlying mechanism may involve decreased absorption of COM API FEB14 CL V8 COR CPO CL                                                 REF BPI 180613 iron from the gastrointestinal tract. During long-term treatment (6 months) with entacapone a clinically significant decrease in haemoglobin has been observed in 1.5% of patients.
Rare reports of clinically significant increases in liver enzymes have been received.
The following adverse drug 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 reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <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).
Psychiatric disorders
Common                  Insomnia, hallucinations, confusion, nightmares Very rare               Agitation
Nervous system disorders
Very common             Dyskinesia
Common                  Parkinsonism aggravated, dizziness, dystonia, hyperkinesia Cardiac disorders
Common                  Ischaemic heart disease events other than myocardial infarction*(e.g. angina pectoris) Uncommon                Myocardial infarction*
Gastrointestinal disorders
Very common             Nausea
Common                  Diarrhoea, abdominal pain, dry mouth, constipation, vomiting Very rare               Anorexia, colitis
Hepato-biliary disorders
Rare                    Hepatic function tests abnormal
Not known               Hepatitis with mainly cholestatic features 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 discolouration
General disorders and administration site conditions
Common                  Fatigue, sweating increased, fall
Very rare               Weight decrease
* The incidence rates of myocardial infarction and other ischaemic 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.

Entacapone used in combination with levodopa has been associated with isolated cases of excessive daytime somnolence and sudden sleep onset episodes (see section 4.7 Effects on ability to drive and use machines).
Isolated cases of neuroleptic malignant syndrome (NMS) have been reported especially following abrupt reduction or discontinuation of entacapone and other dopaminergic medications.
Isolated cases of rhabdomyolysis have been reported.
COM API FEB14 CL V8 COR CPO CL                                                                 REF BPI 180613 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 entacapone in association with levodopa (see section 4.4 Special warnings and precautions for use).