Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile (see also section 4.4)
Most frequent adverse reactions include nausea, vomiting, diarrhoea, fever, rash, anorexia, oral and anal inflammation or ulceration, and hepatic dysfunction.

Blood and lymphatic system disorders:
Because cytarabine is a bone marrow suppressant, anaemia, leukopenia, thrombocytopenia, megaloblastosis and reduced reticulocytes can be expected as a result of its administration.
The severity of these reactions are dose and schedule dependent. Cellular changes in the morphology of bone marrow and peripheral smears can be expected.

Infections and infestations:
Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body, may be associated with the use of Cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe and at times fatal.

Musculoskeletal and connective tissue disorders:
A Cytarabine syndrome has been described. It is characterised by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise. It usually occurs 6 - 12 hours following drug administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated as well as continuation of therapy with cytarabine.

The reported adverse reactions are listed below by MedDRA System Organ Class and by frequency. Frequencies are defined as: Very common (>10%), Common (>1%, ≤10%), Uncommon (>0.1%, ≤1%), Rare (>0.01%, ≤0.1%), and Frequency not known (cannot be estimated from available data).


Adverse Reactions Table
Infections and Infestations:
Very common             Sepsis, pneumonia, infectiona
Frequency not known        Injection site cellulitis, liver abscess
Blood and Lymphatic System Disorders:
Very common             Bone marrow failure, thrombocytopenia, anaemia, anaemia megaloblastic, leukopenia, reticulocyte count decreased
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Immune System Disorders:
Frequency not known       Anaphylactic reaction, allergic oedema
Metabolism and Nutrition Disorders:
Frequency not known       Decreased appetite
Nervous System Disorders:
Frequency not known       Neurotoxicity, neuritis, dizziness, headache Eye Disorders:
Frequency not known       Conjunctivitisb
Cardiac Disorders:
Frequency not known       Pericarditis, sinus bradycardia
Vascular Disorders:
Frequency not known       Thrombophlebitis
Respiratory, Thoracic and Mediastinal Disorders:
Frequency not known       Dyspnoea, oropharyngeal pain
Gastrointestinal Disorders:
Very common            Stomatitis, mouth ulceration, anal ulcer, anal inflammation, diarrhoea, vomiting, nausea, abdominal pain
Frequency not known       Pancreatitis, oesophageal ulcer, oesophagitis Hepatobiliary Disorders:
Very common            Hepatic function abnormal
Frequency not known       Jaundice
Skin and Subcutaneous Tissue Disorders:
Very common            Alopecia, rash
Common               Skin ulcer
Frequency not known       Palmar-plantar erythrodysaesthesia syndrome, urticaria, pruritus, ephelides
Musculoskeletal, Connective Tissue and Bone Disorders:
Very common            Cytarabine syndrome
Renal and Urinary Disorders:
Frequency not known       Renal impairment, urinary retention
General Disorders and Administration Site Conditions:
Very common            Pyrexia
Frequency not known       Chest pain, injection site reactionc
Investigations:
Very common            Biopsy bone marrow abnormal, blood smear test abnormal a may be mild, but can be severe and at times fatal b may occur with rash and may be hemorrhagic with high dose therapy c pain and inflammation at subcutaneous injection site


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Adverse reactions reported in association with high dose therapy (see section 4.4) are included in the following table:

Adverse Reactions Table (High Dose Therapy)
Infections and Infestations:
Frequency not known          Liver abscess, sepsis
Psychiatric Disorders:
Frequency not known           Personality changea
Nervous System Disorders:
Very common               Cerebral disorder, cerebellar disorder, somnolence Frequency not known          Coma, convulsion, peripheral motor neuropathy, peripheral sensory neuropathy
Eye Disorders:
Very common              Corneal disorder
Cardiac Disorders:
Frequency not known          Cardiomyopathyb, sinus bradycardia
Respiratory, Thoracic and Mediastinal Disorders:
Very common              Acute respiratory distress syndrome, pulmonary oedema Gastrointestinal Disorders:
Common                  Necrotising colitis
Frequency not known          Gastrointestinal necrosis, gastrointestinal ulcer, pneumatosis intestinalis, peritonitis
Hepatobiliary Disorders:
Frequency not known          Liver injury, hyperbilirubinaemia
Skin and Subcutaneous Tissue Disorders:
Common                Skin exfoliation,
a personality change was reported in association with cerebral and cerebellar dysfunction.
b with subsequent death

Other adverse reactions
A diffuse interstitial pneumonitis without clear cause that may have been related to cytarabine was reported in patients treated with experimental intermediate doses of cytarabine (1g/m2) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, VP-16).

A syndrome of sudden respiratory distress, rapidly progressing to pulmonary oedema and a radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia; fatal outcome has been reported.


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
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 https://sideeffects.health.gov.il