Adverse reactions : תופעות לוואי

4.8      Undesirable effects

The table below lists the adverse reactions identified through clinical trial experience and post- marketing surveillance by system organ class and frequency. The frequency grouping is 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); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and infestations:
Very common: Infection.
Uncommon: Sepsis/septicaemia.

Neoplasms benign, malignant and unspecified (incl. cysts and polyps): Uncommon: Secondary leukaemia (acute myeloid leukaemia and myelodysplastic syndrome).

Blood and lymphatic system disorders:
Very common: Anaemia, leukopoenia, neutropoenia, febrile neutropoenia, pancytopoenia, thrombocytopoenia.

Immune system disorders:
Very rare: Anaphylaxis.

Metabolism and nutrition disorders:
Very common: Anorexia.
Uncommon: Hyperuricaemia (tumour lysis syndrome), dehydration.
Unknown frequency: Hyperphosphatemia, hyperkalaemia, hypocalcaemia, hyperphosphaturia (tumour lysis syndrome).

Cardiac disorders:
Very common: Sinus tachycardia, tachyarrhythmia, bradycardia, asymptomatic reduced left ventricular ejection fraction.
Common: Cardiomyopathy
Uncommon: ECG abnormalities (including non-specific ST segment changes), myocardial infarction, congestive heart failure.
Very rare: Atrioventricular block, branch block, myocarditis, pericarditis.


Vascular disorders:
Common: Phlebitis, deep vein thrombosis, haemorrhage.
Uncommon: Shock.
Very rare: Hot flushes, pulmonary embolism.
Gastrointestinal disorders:
Very common: Nausea, vomiting and diarrhoea, mucositis/stomatitis, abdominal pain, burning sensations.
Common: Gastrointestinal tract bleeding, colic.
Uncommon: Oesophagitis and colitis (including severe enterocolitis/neutropenic enterocolitis with perforation).
Very rare: Erosion/ulceration.

Skin and subcutaneous tissue disorders:
Local toxicity (frequency not known):
•    In the event of extravasation: local pain, severe tissue damage (blistering, severe inflammation of subcutaneous tissue).
•    In the event of injection site reaction: sclerosis in small vessels.

Very common: Alopecia.
Common: Rash, pruritus, reactivated skin reactions in irradiated zone.
Uncommon: Urticaria, skin and nail hyperpigmentation, cellulitis that could be severe, tissue necrosis.
Very rare: Acral erythema.

Renal and urinary disorders:
Very common: Red discolouration of urine one to two days after administration.
General disorders and administration site conditions:
Very common: Fever, headaches, chills

Investigations:
Very common: Asymptomatic reduced left ventricular ejection fraction, ECG abnormalities (T-wave abnormality).
Common: Increased hepatic enzymes and bilirubin.

Nervous system disorders
Rare: Cerebral haemorrhage.

Haematopoietic system
Marked myelosuppression is the most severe adverse reaction of treatment with ZAVEDOS. This, however, may be necessary to eradicate leukaemia cells (see section 4.4).

Cardiotoxicity
Life-threatening congestive heart failure is the most severe form of cardiomyopathy induced by anthracyclines and represents cumulative dose-limiting toxicity (see section 4.4).

Description of certain undesirable effects
Gastrointestinal
Stomatitis and, in certain serious cases, ulceration of the mucosa, dehydration due to vomiting and severe diarrhoea; risk of perforated colon.

Other undesirable effects: hyperuricaemia
Preventing the symptoms of hyperuricaemia, with hydration, alkalinisation of the urine and prophylaxis with allopurinol may minimise the potential complications of tumour lysis syndrome.

The undesirable effects are similar in adults and children, except that there is a greater susceptibility to anthracycline-induced cardiac toxicity in children.

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 https://sideeffects.health.gov.il