Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
In clinical trials (in which a total of 1,931 patients were taking Circadin and 1,642 patients were taking placebo), 48.8% of patients receiving Circadin reported an adverse reaction compared with 37.8% taking placebo. Comparing the rate of patients with adverse reactions per 100 patient weeks, the rate was higher for placebo than Circadin (5.743– placebo vs. 3.013– Circadin). The most common adverse reactions were headache, nasopharyngitis, back pain, and arthralgia , which were common, by MedDRA definition, in both the Circadin and placebo treated groups.

Tabulated list of adverse reactions
The following adverse reactions were reported in clinical trials and from post-marketing spontaneous reporting.
In clinical trials a total of 9.5% of patients receiving Circadin reported an adverse reaction compared with 7.4% of patients taking placebo. Only those adverse reactions reported during clinical trials occurring in patients at an equivalent or greater rate than placebo have been included below.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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 established from the available data).

System Organ       Very       Common         Uncommon                    Rare               Not known: Class         Common                                                                     (Cannot be established from the available data)
Infections and                                                   Herpes zoster infestations
Blood and                                                        Leukopenia, lymphatic                                                        thrombocytopenia system disorders
Immune system                                                                               Hyper- disorders                                                                                   sensitivity reaction
Metabolism and                                                   Hypertriglyceridaemia, nutrition                                                        hypocalcaemia, disorders                                                        hyponatraemia Psychiatric                               Irritability,          Mood altered, disorders                                 nervousness,           aggression, agitation, restlessness,          crying, stress insomnia, abnormal     symptoms,
dreams, nightmares,    disorientation, early anxiety                morning awakening,
libido increased,
depressed mood,
depression
Nervous system                            Migraine, headache,    Syncope, memory disorders                                 lethargy,              impairment, psychomotor            disturbance in hyperactivity,         attention, dreamy state,
dizziness,             restless legs syndrome,
somnolence             poor quality sleep,
paraesthesia
Eye disorders                                                    Visual acuity reduced, vision blurred,
lacrimation increased
Ear and                                                          Vertigo positional, labyrinth                                                        vertigo disorders
Cardiac                                                          Angina pectoris, disorders                                                        palpitations Vascular                                  Hypertension           Hot flush disorders


System Organ        Very       Common          Uncommon                     Rare             Not known: Class          Common                                                                     (Cannot be established from the available data)
Gastrointestinal                           Abdominal pain,         Gastro-oesophageal disorders                                  abdominal pain          reflux disease, upper, dyspepsia,       gastrointestinal mouth ulceration,       disorder, oral mucosal dry mouth, nausea       blistering, tongue ulceration,
gastrointestinal upset,
vomiting, bowel sounds abnormal,
flatulence, salivary hypersecretion,
halitosis, abdominal discomfort, gastric disorder, gastritis
Hepatobiliary                              Hyperbilirubinaemia disorders
Skin and                                   Dermatitis, night       Eczema, erythema,         Angioedema, subcutaneous                               sweats, pruritus,       hand dermatitis,          oedema of tissue disorders                           rash, pruritus          psoriasis, rash           mouth, tongue generalised, dry skin   generalised, rash         oedema pruritic, nail disorder
Musculoskeletal                            Pain in extremity       Arthritis, muscle and connective                                                     spasms, neck pain, tissue disorders                                                   night cramps Renal and                                  Glycosuria,             Polyuria, haematuria, urinary disorders                          proteinuria             nocturia Reproductive                               Menopausal              Priapism, prostatitis     Galactorrhoea system and                                 symptoms breast disorders
General                                    Asthenia, chest pain    Fatigue, pain, thirst disorders and administration site conditions
Investigations                             Liver function test     Hepatic enzyme abnormal, weight        increased, blood increased               electrolyes abnormal,
laboratory test abnormal

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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic @moh.gov.il