Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,778 Parkinson’s disease patients on pramipexole and 1,297 patients on placebo, adverse drug reactions were frequently reported for both groups. 67% of patients on pramipexole and 54% of patients on placebo reported at least one adverse drug reaction.

The majority of adverse drug reactions usually start early in therapy and most tend to disappear even as therapy is continued.

Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: 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).

The most commonly (≥ 5%) reported adverse drug reactions in patients with Parkinson’s disease more frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue. The incidence of somnolence is increased at doses higher than 1.5 mg pramipexole salt per day (see section 4.2). A more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.

Body System      Very common        Common               Uncommon              Rare       Not known (≥1/10)         (≥1/100 to           (≥1/1,000 to       (≥1/10,000 <1/10)               < 1/100)        to <1/1,000)
Infections and                                          pneumonia infestations
Endocrine                                               inappropriate disorders                                               antidiuretic hormone secretion1
Psychiatric                       insomnia,             compulsive         mania disorders                         hallucinations,       shopping,
abnormal              pathological dreams,               gambling,
confusion             restlessness,
hypersexuality,
behavioural           delusion,
symptoms of           libido disorder,
impulse control       paranoia,
disorders and         delirium,
compulsions           binge eating1,
hyperphagia1
Nervous system    somnolence      headache              sudden onset of disorders         dizziness                             sleep,
dyskinesia                            amnesia,
hyperkinesia,
syncope
Eye disorders                     visual impairment including diplopia,
vision blurred,
visual acuity reduced
Cardiac                                                cardiac failure1 disorders
Vascular                         hypotension disorders
Respiratory,                                           dyspnoea,
thoracic, and                                          hiccups
mediastinal disorders
Gastrointestinal   nausea       constipation,
disorders                       vomiting
Skin and                                              hypersensitivity, subcutaneous                                          pruritus,
tissue disorders                                      rash
Reproductive                                                              spontaneous system and                                                                penile erection breast disorder
General                         fatigue,                                                    dopamine disorders and                   peripheral                                                  agonist administration                  oedema                                                      withdrawal site conditions                                                                             syndrome including apathy,
anxiety,
depression,
fatigue,
sweating and pain.
Investigations                  weight decrease       weight increase including decreased appetite
1
This side effect has been observed in post-marketing experience. With 95 % certainty, the frequency category is not greater than uncommon, but might be lower. A precise frequency estimation is not possible as the side effect did not occur in a clinical trial database of 2,762 patients with Parkinson’s Disease treated with pramipexole.

Description of selected adverse reactions
Somnolence
Pramipexole is commonly associated with somnolence and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes (see also section 4.4).

Libido disorders
Pramipexole may uncommonly be associated with libido disorders (increased or decreased).

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 including SIFROL (see section 4.4).

In a cross-sectional, retrospective screening and case-control study including 3,090 Parkinson’s disease patients, 13.6% of all patients receiving dopaminergic or non-dopaminergic treatment had symptoms of an impulse control disorder during the past six months. Manifestations observed include pathological gambling, compulsive shopping, binge eating, and compulsive sexual behaviour (hypersexuality). Possible independent risk factors for impulse control disorders included dopaminergic treatments and higher doses of dopaminergic treatment, younger age (≤ 65 years), not being married and self-reported family history of gambling behaviours.

Dopamine agonist withdrawal syndrome
Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including pramipexole. Symptoms include apathy, anxiety, depression, fatigue, sweating and pain (see section 4.4).

Cardiac failure
In clinical studies and post-marketing experience cardiac failure has been reported in patients with pramipexole. In a pharmacoepidemiological study pramipexole use was associated with an increased risk of cardiac failure compared with non-use of pramipexole (observed risk ratio 1.86; 95% CI, 1.21- 2.85).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il.