Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,923 patients on pramipexole and 1,354 patients on placebo, adverse drug reactions were frequently reported for both groups. 63% of patients on pramipexole and 52% 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.

Sifrol IR                                                                        Updated Prescribing Information 0.25 mg, 1 mg                                                                                         April 2020 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).

Parkinson's disease, most common adverse reactions
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.


Table 1: Parkinson’s disease
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,
behavioural       hypersexuality,
symptoms of       delusion,
impulse control   libido disorder,
disorders and     paranoia,
compulsions       delirium,
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, Sifrol IR                                                                                         Updated Prescribing Information 0.25 mg, 1 mg                                                                                                          April 2020 subcutaneous                                                      Pruritus, tissue disorders                                                  rash 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.

Restless Legs Syndrome, most common adverse reactions
The most commonly ( 5%) reported adverse drug reactions in patients with Restless Legs Syndrome treated with Pramipexole were nausea, headache, dizziness and fatigue. Nausea and fatigue were more often reported in female patients treated with SIFROL (20.8% and 10.5%, respectively) compared to males (6.7% and 7.3%, respectively).


Table 2: Restless Legs Syndrome
Body              Very common             Common              Uncommon (≥1/1,000 to <                Not known System                (≥1/10)              (≥1/100 to                 1/100) <1/10)
Infections and                                                 pneumonia1 infestations

Endocrine                                                      inappropriate antidiuretic disorders                                                      hormone secretion1 

Psychiatric                                  Insomnia,         Restlessness, confusion, disorders                                    abnormal          hallucinations, libido disorder, dreams            delusion1, hyperphagia1, paranoia1
, mania1 , delirium1, behavioural symptoms of impulse control disorders and compulsions1 (such as: compulsive shopping,
pathological gambling,
hypersexuality, binge eating)
Nervous                                      Headache,         sudden onset of sleep, syncope, system                                       dizziness,        dyskinesia, amnesia1, disorders                                    somnolence        hyperkinesia1 
Eye disorders                                                  visual impairment including visual acuity,
reduced diplopia,
vision blurred

Sifrol IR                                                                                Updated Prescribing Information 0.25 mg, 1 mg                                                                                                 April 2020 Cardiac                                                  cardiac failure1 disorders
Vascular                                                 Hypotension disorders
Respiratory,                                             Dyspnoea, hiccups thoracic, and mediastinal disorders
Gastrointestina nausea                   constipation,
l disorders                              vomiting
Skin and                                                 Hypersensitivity, pruritus, rash subcutaneous tissue disorders

General                                  fatigue         peripheral oedema                  Dopamine disorders and                                                                               agonist administration                                                                              withdrawal site conditions                                                                             syndrome including apathy, anxiety,
depression,
fatigue,
sweating and pain

Investigations                                           weight decrease including decreased appetite weight increase

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 1,395 patients with Restless Legs Syndrome 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 Sifrol IR                                                                        Updated Prescribing Information 0.25 mg, 1 mg                                                                                         April 2020 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).


You can report side effects to the Ministry of Health by following the link ‘Reporting Side Effects of Drug Treatment' on the Ministry of Health home page (www.health.gov.il) which links to an online form for reporting side effects. You can also use this link: https://sideeffects.health.gov.il