Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Depressed patients display a number of symptoms that are associated with the illness itself. It is therefore sometimes difficult to ascertain which symptoms are a result of the illness itself and which are a result of treatment with Remeron.
The most commonly reported adverse reactions, occurring in more than 5 % of patients treated with Remeron in randomized placebo-controlled trials (see below) are somnolence, sedation, dry mouth, weight increased, increase in appetite, dizziness and fatigue.
All randomized placebo-controlled trials in patients (including indications other than major depressive disorder), have been evaluated for adverse reactions of Remeron.
The meta-analysis considered 20 trials, with a planned duration of treatment up to 12 weeks, with 1,501 patients (134 person years) receiving doses of mirtazapine up to 60 mg and 850 patients (79 person years) receiving placebo.
Extension phases of these trials have been excluded to maintain comparability to placebo treatment.
Table 1 shows the categorized incidence of the adverse reactions, which occurred in the clinical trials statistically significantly more frequently during treatment with Remeron than with placebo, added with adverse reactions from spontaneous reporting. The frequencies of the adverse reactions from spontaneous reporting are based on the reporting rate of these events in the clinical trials. The frequency of adverse reactions from spontaneous reporting for which no cases in the randomized placebo-controlled patient trials were observed with mirtazapine has been classified as ‘not known’.
Table 1.              Adverse reactions of Remeron.
System organ         Very common              Common                 Uncommon               Rare               Frequency not class                (≥1/10)                  (≥1/100 to             (≥1/1,000 to           (≥1/10,000 to      Known (cannot be <1/10)                 ≤1/100)                ≤1/1,000)          estimated from the available data)
Blood and the                                                                                                   Bone marrow lymphatic                                                                                                        depression system                                                                                                           (granulocytopenia, disorders                                                                                                        agranulocytosis, aplastic anaemia,
thrombocytopenia)
 Eosinophilia
Endocrine                                                                                                       Inappropriate disorders                                                                                                        antidiuretic hormone secretion
Metabolism and        Weight                                                                                   Hyponatraemia 1 nutrition              increased disorders             Increase in
1 appetite
2                                                6
Psychiatric                                    Abnormal              Nightmares            Aggression        Suicidal ideation disorders                                       dreams                Mania                                    Suicidal 2                                          6
 Confusion             Agitation                                 behaviour 2, 5
 Anxiety               Hallucinations
3, 5
 Insomnia              Psychomotor restlessness
(incl. akathisia,
hyperkinesia)
1, 4                1                            2
Nervous system        Somnolence              Lethargy              Paraesthesia          Myoclonus         Convulsions 1, 4 disorders             Sedation                Dizziness             Restless legs                             (insults) 2
 Headache                Tremor                Syncope                                  Serotonin syndrome
 Oral paresthesia
 Dysarthria
2
Vascular                                           Orthostatic       Hypotension disorders                                           hypotension
3
Gastrointestinal      Dry mouth                 Nausea              Oral hypo-              Pancreatitis    Mouth oedema 2 disorders                                        Diarrhea             aesthesia                                Increased 2
   Vomiting                                                       salivation 1
   Constipation
Hepatobiliary                                                                                Elevations in disorders                                                                                     serum transaminase activities
2
Skin and                                           Exanthema                                                    Stevens- Johnson subcutaneous                                                                                                      Syndrome tissue disorders                                                                                                 Dermatitis bullous
 Erythema multiforme
 Toxic epidermal necrolysis
Musculoskeletal                                Arthralgia                                                      Rhabdomyolysis and connective                                 Myalgia
1 tissue disorders                               Back pain
Renal and                                                                                                       Urinary retention urinary disorders
General                                        Oedema                                                          Somnambulism 1 disorders and                                   peripheral                                                      Generalised administration                                 Fatigue                                                          oedema site conditions                                                                                                 Localised oedema Investigations                                                                                                  Increased creatine kinase
1
In clinical trials these events occurred statistically significantly more frequently during treatment with Remeron than with placebo.
2
In clinical trials these events occurred more frequently during treatment with placebo than with Remeron, however not statistically significantly more frequently.
3
In clinical trials these events occurred statistically significantly more frequently during treatment with placebo than with Remeron.
4 N.B. dose reduction generally does not lead to less somnolence/sedation but can jeopardize antidepressant efficacy.
5 Upon treatment with antidepressants in general, anxiety and insomnia (which may be symptoms of depression) can develop or become aggravated. Under mirtazapine treatment, development or aggravation of anxiety and insomnia has been reported.
6 Cases of suicidal ideation and suicidal behaviours have been reported during mirtazapine therapy or early after treatment discontinuation (see section 4.4).

In laboratory evaluations in clinical trials transient increases in transaminases and gamma- glutamyltransferase have been observed (however associated adverse events have not been reported statistically significantly more frequently with Remeron than with placebo).

Paediatric population
The following adverse events were observed commonly in clinical trials in children: weight gain, urticaria and hypertriglyceridaemia (see also section 5.1).

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=AdversEffect Medic@moh.gov.il