Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
The most commonly reported adverse drug reactions (ADRs) are gastrointestinal, including nausea (38%) and vomiting (23%), especially during titration. Female patients in clinical studies were found to be more susceptible to gastrointestinal adverse reactions and weight loss.


Tabulated list of adverse reactions
Adverse reactions in Table 1 and Table 2 are listed according to the MedDRA system organ class and frequency category. Frequency categories are defined 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).
The following adverse reactions, listed below in Table 1, have been accumulated in patients with Alzheimer’s dementia treated with Exelon.
Table 1
Infections and infestations
Very rare                        Urinary infection
Metabolism and nutrition disorders
Very common                         Anorexia
Common                              Decreased appetite
Not known                           Dehydration
Psychiatric disorders
Common                              Nightmares
Common                              Agitation
Common                              Confusion
Common                              Anxiety
Uncommon                            Insomnia
Uncommon                            Depression
Very rare                           Hallucinations
Not known                           Aggression, restlessness
Nervous system disorders
Very common                         Dizziness
Common                              Headache
Common                              Somnolence
Common                              Tremor
Uncommon                            Syncope
Rare                                Seizures
Very rare                           Extrapyramidal symptoms (including worsening of Parkinson’s disease)
Cardiac disorders
Rare                                Angina pectoris
Very rare                           Cardiac arrhythmia (e.g. bradycardia, atrio-ventricular block, atrial fibrillation and tachycardia)
Not known                           Sick sinus syndrome
Vascular disorders
Very rare                           Hypertension



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        Gastrointestinal disorders
Very common                        Nausea
Very common                        Vomiting
Very common                        Diarrhoea
Common                             Abdominal pain and dyspepsia
Rare                               Gastric and duodenal ulcers
Very rare                          Gastrointestinal haemorrhage
Very rare                          Pancreatitis
Not known                          Some cases of severe vomiting were associated with oesophageal rupture (see section 4.4)
.
Hepatobiliary disorders
Uncommon                      Elevated liver function tests
Not known                     Hepatitis
Skin and subcutaneous tissue disorders
Common                        Hyperhydrosis
Rare                          Rash
Not known                     Pruritus, allergic dermatitis (disseminated) General disorders and administration site conditions
Common                        Fatigue and asthenia
Common                        Malaise
Uncommon                      Fall
Investigations
Common                           Weight loss

The following additional adverse reactions have been observed with Exelon transdermal patches: delirium, pyrexia, decreased appetite, urinary incontinence (common), psychomotor hyperactivity (uncommon), erythema, urticaria, vesicles, allergic dermatitis (not known).

Table 2 shows the adverse reactions reported during clinical studies conducted in patients with dementia associated with Parkinson’s disease treated with Exelon capsules.

Table 2
Metabolism and nutrition disorders
Common                            Decreased appetite
Common                            Dehydration
Psychiatric disorders
Common                            Insomnia
Common                            Anxiety
Common                            Restlessness
Common                            Hallucination, visual
Common                            Depression Aggression
Not known
Nervous system disorders
Very common                        Tremor
Common                             Dizziness
Common                             Somnolence
Common                             Headache
Common                             Parkinson’s disease (worsening)
Common                             Bradykinesia
Common                             Dyskinesia
Common                             Hypokinesia
Common                             Cogwheel rigidity
Uncommon                           Dystonia



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        Cardiac disorders
Common                        Bradycardia
Uncommon                      Atrial Fibrillation
Uncommon                      Atrioventricular block
Not known                     Sick sinus syndrome
Vascular disorders
Common                        Hypertension
Uncommon                      Hypotension
Gastrointestinal disorders
Very common                   Nausea
Very common                   Vomiting
Common                        Diarrhoea
Common                        Abdominal pain and dyspepsia
Common                        Salivary hypersecretion
Hepatobiliary disorders
Not known                     Hepatitis
Skin and subcutaneous tissue disorders
Common                        Hyperhydrosis
Not known                     Allergic dermatitis (disseminated)
General disorders and administration site conditions
Very common                   Fall
Common                        Fatigue and asthenia
Common                        Gait disturbance
Common                        Parkinson gait
The following additional adverse reaction has been observed in a study of patients with dementia associated with Parkinson’s disease treated with Exelon transdermal patches: agitation (common).

Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted with Exelon in patients with dementia associated with Parkinson’s disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.

Table 3

Pre-defined adverse events that may reflect         Exelon                           Placebo worsening of parkinsonian symptoms in patients with     n(%)                          n (%) dementia associated  with
Total patients    Parkinson’s disease studied                                  362 (100)                   179 (100) Total patients with pre-defined AE(s)                    99 (27.3)                  28 (15.6) Tremor                                               37 (10.2)                       7 (3.9) Fall                                                  21 (5.8)                       11 (6.1) Parkinson’s disease (worsening)                       12 (3.3)                       2 (1.1) Salivary hypersecretion                                     5                           0 Dyskinesia                                                 (1.
5                        1 (0.6)
Parkinsonism                                               4)
8
(1.                       1 (0.6)
Hypokinesia                                                (2.
4)
1                           0
Movement disorder                                          2)
(0.
1                           0
Bradykinesia                                               (0.
3)
9                        3 (1.7)
Dystonia                                                   3)
(2.
3                        1 (0.6)
Gait abnormality                                           5)
(0.
5                           0
Muscle rigidity                                            (1.
8)
1                           0
Balance disorder                                           4)
(0.
3                        2 (1.1)
Musculoskeletal stiffness                                  (0.
3)
3                           0
Rigors                                                     8)
(0.
1                           0
Motor dysfunction                                          8)
(0.
1                           0
(0.3
3)
Reporting of suspected adverse reactions                      )
Reporting suspected adverse reactions after authorization of the medicinal product is important. It 
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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/