Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Application site skin reactions (usually mild to moderate application site erythema), are the most frequent adverse reactions observed with the use of Exelon transdermal patch. The next most common adverse reactions are gastrointestinal in nature including nausea and vomiting.

Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: 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).

Tabulated list of adverse reactions

Table 1 displays the adverse reactions reported in 1,670 patients with Alzheimer’s dementia treated in randomised, double-blind, placebo and active-controlled clinical studies with Exelon transdermal patches for a duration of 24-48 weeks and from post-marketing data.


EXE APL JUL23 V11                         Page 6 of 14                      EU SmPC Apr.2023 Table 1

Infections and infestations
Common                 Urinary tract infection
Metabolism and nutrition disorders
Common                 Anorexia, decreased appetite
Uncommon               Dehydration
Psychiatric disorders
Common                 Anxiety, depression, delirium, agitation
Uncommon               Aggression
Not known              Hallucinations, restlessness, nightmares
Nervous system disorders
Common                 Headache, syncope, dizziness
Uncommon               Psychomotor hyperactivity
Very rare              Extrapyramidal symptoms
Not known              Worsening of Parkinson’s disease, seizure, tremor, somnolence Cardiac disorders
Uncommon               Bradycardia
Not known              Atrioventricular block, atrial fibrillation, tachycardia, sick sinus syndrome
Vascular disorders
Not known              Hypertension
Gastrointestinal disorders
Common                 Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain Uncommon               Gastric ulcer
Not known              Pancreatitis
Hepatobiliary disorders
Not known              Hepatitis, elevated liver function tests
Skin and subcutaneous tissue disorders
Common                 Rash
Not known              Pruritus, erythema, urticaria, vesicles, allergic dermatitis (disseminated)
Renal and urinary disorders
Common                 Urinary incontinence
General disorders and administration site conditions
Common                 Application site skin reactions (e.g. application site erythema*, application site pruritus*, application site oedema*, application site dermatitis, application site irritation), asthenic conditions (e.g. fatigue, asthenia), pyrexia, weight decreased
Rare                   Fall
*In a 24-week controlled study in Japanese patients, application site erythema, application site oedema and application site pruritus were reported as “very common”.

Description of selected adverse reactions

When doses higher than 13.3 mg/24 h (Exelon patch 15) were used in the above-mentioned placebo- controlled study, insomnia and cardiac failure were observed more frequently than with 13.3 mg/24 h (Exelon patch 15) or placebo, suggesting a dose effect relationship. However, these events did not occur at a higher frequency with Exelon 13.3 mg/24 h transdermal patches (Exelon patch 15) than with placebo.

The following adverse reactions have only been observed with Exelon capsules and oral solution and not in clinical studies with Exelon transdermal patches: malaise, confusion, sweating increased (common); duodenal ulcers, angina pectoris (rare); gastrointestinal haemorrhage (very rare); and some cases of severe vomiting were associated with oesophageal rupture (not known).

Skin irritation
In double-blind controlled clinical trials, application site reactions were mostly mild to moderate in EXE APL JUL23 V11                          Page 7 of 14                      EU SmPC Apr.2023 severity. The incidence of application site skin reactions leading to discontinuation was ≤2.3% in patients treated with Exelon transdermal patches. The incidence of application site skin reactions leading to discontinuation was higher in the Asian population with 4.9% and 8.4% in the Chinese and Japanese population respectively.

In two 24-week double-blind, placebo-controlled clinical trials, skin reactions were measured at each visit using a skin irritation rating scale. When observed in patients treated with Exelon transdermal patches, skin irritation was mostly slight or mild in severity. It was rated as severe in ≤2.2% of patients in these studies and in ≤3.7% of patients treated with Exelon transdermal patches in a Japanese study.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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/