Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile
Headache, abdominal pain, diarrhoea and nausea are among those adverse reactions that have been most commonly reported in clinical trials (and also from post-marketing use). In addition, the safety profile is similar for different formulations, treatment indications, age groups and patient populations. No dose-related adverse reactions have been identified.


Tabulated list of adverse reactions
The following adverse medicinal product reactions have been identified or suspected in the clinical trials programme for esomeprazole administered orally or intravenously and post- marketing when administered orally. The reactions are classified according to frequency: 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).



System Organ Class                Frequency      Undesirable Effect Blood and lymphatic system        Rare           Leukopenia, thrombocytopenia disorders                         Very rare      Agranulocytosis, pancytopenia Immune system disorders           Rare           Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock
Metabolism and nutrition          Uncommon       Peripheral oedema disorders                         Rare           Hyponatraemia
Not known      Hypomagnesaemia (see section 4.4); severe hypomagnesaemia can correlate with hypocalcaemia. Hypomagnesaemia may also be associated with hypokalaemia.
Psychiatric disorders             Uncommon       Insomnia
Rare        Agitation, confusion, depression
Very rare   Aggression, hallucinations

Nervous system disorders      Common      Headache
Uncommon    Dizziness, paraesthesia, somnolence
Rare        Taste disturbance
Eye disorders                 Uncommon    Blurred vision
Ear and labyrinth disorders   Uncommon    Vertigo
Respiratory, thoracic and     Rare        Bronchospasm mediastinal disorders
Gastrointestinal disorders    Common      Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting, fundic gland polyps (benign)
Uncommon    Dry mouth
Rare        Stomatitis, gastrointestinal candidiasis
Not known   Microscopic colitis
Hepatobiliary disorders       Uncommon    Increased liver enzymes
Rare        Hepatitis with or without jaundice
Very rare   Hepatic failure, encephalopathy in patients with pre-existing liver disease
Skin and subcutaneous         Common      Administration site reactions* tissue disorders              Uncommon    Dermatitis, pruritus, rash, urticaria Rare        Alopecia, photosensitivity
Very rare   Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)
Not known   Subacute cutaneous lupus erythematosus
(see section 4.4)
Musculoskeletal and           Uncommon    Fracture of the hip, wrist or spine (see connective tissue disorders               section 4.4)
Rare        Arthralgia, myalgia
Very rare   Muscular weakness
Renal and urinary disorders   Very rare   Interstitial nephritis: in some patients, renal failure has been reported concomitantly
Reproductive system and       Very rare   Gynaecomastia breast disorders
General disorders and         Rare        Malaise, increased sweating administration site
conditions


*Administration site reactions have mainly been observed in a study with high-dose exposure over 3 days (72 hours) (see section 5.3).


Irreversible visual impairment has been reported in isolated cases of critically ill patients who have received omeprazole (the racemate) intravenous injection, especially at high doses, but no causal relationship has been established.


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: https://sideeffects.health.gov.il


Paediatric population
A randomised, open-label, multi-national study was conducted to evaluate the pharmacokinetics of repeated intravenous doses for 4 days of once daily esomeprazole in paediatric patients 0 to 18 years old (see section 5.2). A total of 57 patients (8 children in the age group 1– 5 years) were included for safety evaluation. The safety results are consistent with the known safety profile of esomeprazole, and no new safety signals were identified.