Adverse reactions : תופעות לוואי

4.8       Undesirable effects

Summary of safety profile
Based on the experience with the use of fludarabine, the most common adverse events include myelosuppression (neutropenia, thrombocytopenia and anaemia), infection including pneumonia, cough, fever, fatigue, weakness, nausea, vomiting and diarrhoea. Other commonly reported events include chills, oedema, malaise, peripheral neuropathy, visual disturbance, anorexia, mucositis, stomatitis and skin rash.
Serious opportunistic infections have occurred in patients treated with fludarabine. Fatalities as a consequence of serious adverse events have been reported.

Tabulated list of adverse reactions
The table below reports adverse events by MedDRA system organ classes (MedDRA SOCs). The frequencies are based on clinical trial data regardless of the causal relationship with fludarabine. The rare adverse reactions were mainly identified from the post-marketing experience.

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)
Not known          (cannot be estimated from the available data)


System          Very Common        Common             Uncommon         Rare Organ
Class
MedDRA and
Infections      Infections /                                           Lymphoproliferat infestations    Opportunistic                                          i disorder ve infections (like                                       (EBV- associated) latent viral reactivation,
e.g. progressive multifocal leucoencephalo pathy, herpes zoster virus,
Epstein-Barr- virus),
pneumonia



System Organ Very Common         Common               Uncommon                Rare Class
MedDRA
Neoplasms                        Myelodysplastic benign,                          syndrome and malignant                        acute myeloid and unspecified                  leukaemia (mainly
(incl cysts and                  associated with polyps)                          prior, concomitant or subsequent treatment with alkylating agents,
topoisomerase inhibitors or irradiation)
Blood and         Neutropenia,   Myelo-suppression lymphatic         anaemia,
system            thrombo- disorders         cytopenia
Immune system                                       Autoimmune disorder disorders                                           (including autoimmune haemolytic anaemia,
Evans syndrome,
thrombocytopenic purpura, acquired haemophilia,
pemphigus)
Metabolism                       Anorexia           Tumour lysis syndrome and nutrition                                       (including renal failure, disorders                                           metabolic acidosis, hyperkalaemia,
hypocalcemia,
hyperuricemia,
haematuria, urate crystalluria,
hyperphosphatemia)
Nervous system                   Neuropathy         Confusion                 Coma, seizures, disorders                        peripheral                                   agitation Eye disorders                    Visual disturbance                           Blindness, optic neuritis, optic neuropathy
Cardiac                                                                       Heart failure, disorders                                                                     arrhythmia Respiratory,      Cough                             Pulmonary toxicity thoracic and                                        (including pulmonary mediastinal                                         fibrosis, pneumonitis, disorders                                           dyspnoea)
Gastro-           Vomiting,      Stomatitis         Gastrointestinal intestinal        diarrhoea,                        haemorrhage,
disorders         nausea                            pancreatic enzymes abnormal



System Organ Very Common Common                         Uncommon                  Rare Class
MedDRA
Hepatobiliary                                           Hepatic enzyme disorders                                               abnormal
Skin and                 Rash                                                     Skin cancer, subcutaneous                                                                      necrolysis tissue disorders                                                                  epidermal toxic (Lyell type),
Stevens-Johnson
Syndrome
Renal and urinary disorder
General           Fever,           Oedema,
disorders         fatigue,         mucositis,
and               weakness         chills, malaise administrati on site conditions


The most appropriate MedDRA term to describe a certain adverse event is listed. Synonyms or related conditions are not listed, but should be taken into account as well. Adverse event term representation is based on MedDRA version 12.0.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Postmarketing experience with frequency unknown
•       Nervous system disorders
 o       Cerebral haemorrhage o       Leukoencephalopathy (see section 4.4) o       Acute toxic leukoencephalopathy (see section 4.4) o       Reversible posterior leukoencephalopathy syndrome (RPLS) (see section 4.4) 
Respiratory, thoracic and mediastinal disorders
 o       Pulmonary haemorrhage
•       Renal and urinary disorder
 o       Haemorrhagic cystitis

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 via the following link: https://sideeffects.health.gov.il/