Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The following adverse drug reactions are based on post marketing data. They are listed in the table according to MedDRA system organ class and by frequency.
Side effect frequencies are based on the following categories:
Very common:                                Common:
( 1/10)                                    ( 1/100 to < 1/10) Uncommon:                                   Rare:
( 1/1,000 to < 1/100)                      ( 1/10,000 to < 1/1,000) Very rare:
(< 1/10,000)
Unknown:
Unknown (adverse reactions reported in the post-marketing experience) 

Adverse drug reactions
System organ class                          Side effect                        Frequency Infections and             Infections1                                        Common infestations               Pneumonias2                                        Uncommon Sepsis1                                            Uncommon
Septic shock                                       Unknown


Adverse drug reactions
System organ class                       Side effect                        Frequency Neoplasms benign,        Secondary tumors                                   Rare malignant and            Acute leukemia3                                    Rare unspecified (including
Myelodysplastic syndrome                           Rare incl cysts and polyps)
Bladder cancer                                     Rare
Tumor lysis syndrome                               Unknown
Blood and lymphatic      Myelosuppression4                                  Very common system disorders         Disseminated intravascular coagulation (DIC)       Very rare Hemolytic uremic syndrome                          Very common
Lymphopenia                                        Unknown

Immune system            Immunosuppression                                  Very common disorders                Hypersensitivity reactions                         Uncommon Anaphylactic/anaphylactoid reaction                Very rare
Endocrine disorders      Syndrome of inadequate ADH secretion               Rare (SIADH)
Metabolism and           Anorexia                                           Uncommon nutrition disorders      Dehydration                                        Rare Hyponatremia                                       Very rare
Fluid retention                                    Very rare
Changes in blood glucose level (increase or        Unknown decrease)

Psychiatric diseases     Confusion                                          Very rare Nervous system           Dizziness                                          Rare disorders                Convulsion                                         Very rare Encephalopathy                                     Unknown
Neurotoxicity5                                     Unknown
Eye disorders            Visual impairment                                  Rare Conjunctivitis                                     Very rare
Eye edema                                          Very rare
Lacrimation increased                              Unknown

Ear and labyrinth        Deafness                                           Unknown disorders                Tinnitus                                           Unknown Cardiac disorders        Cardiomyopathy                                     Unknown Myocarditis                                        Unknown
Cardiac failure (including isolated fatal cases)   Unknown
Arrhythmias6                                       Unknown
Myocardial infarction                              Unknown


Adverse drug reactions
System organ class                    Side effect                    Frequency Pericarditis                                 Unknown
Cardiogenic shock                            Unknown
Pericardial effusion                         Unknown
Electrocardiogram QT interval prolonged      Unknown
Ventricular fibrillation                     Unknown
Ventricular tachycardia                      Unknown
Vascular disorders      Flushing                                     Uncommon Pulmonary embolism                           Unknown
Venous thrombosis                            Unknown
Vasculitis                                   Unknown
Peripheral ischemia                          Unknown
Respiratory, thoracic   Acute respiratory distress syndrome (ARDS)   Unknown and mediastinal         Pulmonary edema                              Unknown disorders               Pulmonary hypertension                       Unknown Bronchospasm                                 Unknown
Dyspnea                                      Unknown
Hypoxia                                      Unknown
Cough                                        Unknown
Nasal congestion                             Unknown
Rhinorrhea                                   Unknown
Pulmonary veno-occlusive disease             Unknown
Interstitial Lung Diseases7                  Unknown
Oropharyngeal pain                           Unknown
Gastrointestinal        Stomatitis                                   Very rare disorders               Diarrhea                                     Very rare Vomiting                                     Very rare
Constipation                                 Very rare
Nausea                                       Very rare
Hemorrhagic enterocolitis                    Very rare
Acute pancreatitis                           Very rare
Mucosal ulceration                           Very rare
Gastrointestinal hemorrhage                  Unknown
Abdominal pain                               Unknown
Parotid gland inflammation                   Unknown
Colitis                                      Unknown
Enteritis                                    Unknown
Cecitis                                      Unknown


Adverse drug reactions
System organ class                       Side effect                       Frequency Hepatobiliary disorders   Hepatic function abnormal                        Common Veno-occlusive disorder                          Unknown
Hepatitis                                        Unknown
Cholestasis                                      Unknown
Hepatotoxicity8                                  Unknown
Skin and subcutaneous     Alopecia                                         Very common tissue disorders          Dermatitis                                       Rare Discoloration of palms, fingernails, and soles   Rare of the feet
Stevens Johnson syndrome (SJS)                   Very rare
Toxic epidermal necrolysis (TEN)                 Very rare
Erythema multiforme                              Unknown
Radiation recall dermatitis                      Unknown
Pruritus (including inflammatory itching)        Unknown
Palmar-plantar erythrodysesthesia                Unknown
Urticaria                                        Unknown
Blistering                                       Unknown
Facial swelling                                  Unknown
Hyperhidrosis                                    Unknown
Rash                                             Rare
Erythema in irradiated area                      Unknown
Erythema                                         Unknown
Musculoskeletal and       Rhabdomyolysis                                   Unknown connective tissue         Scleroderma                                      Unknown disorders                 Muscle spasms                                    Unknown Myalgia                                          Unknown
Arthralgia                                       Unknown
Renal and urinary         Cystitis                                         Very common disorders                 Microhematuria                                   Very common Hemorrhagic cystitis (including isolated fatal   Common cases)
Macrohematuria                                   Common
Suburethral bleeding                             Very rare
Edema of the bladder wall                        Very rare
Interstitial inflammation with fibrosis and      Very rare sclerosis of the bladder
Renal failure                                    Very rare
Blood creatinine increased                       Very rare

Adverse drug reactions
System organ class                         Side effect           Frequency Renal Tubular necrosis                Unknown
Renal tubular disorder                Unknown
Toxic nephropathy                     Unknown
Hemorrhagic ureteritis                Unknown
Ulcerative cystitis                   Unknown
Bladder contracture                   Unknown
Nephrogenic diabetes insipidus        Unknown
Atypical bladder epithelial cells     Unknown
Blood urea nitrogen increased         Unknown
Pregnancy, puerperium      Premature labor                       Unknown and perinatal conditions
Reproductive system        Impairment of spermatogenesis         Common and breast disorders       Ovulation disorder                    Uncommon Amenorrhea9                           Rare
Azoospermia9                          Rare
Oligospermia9                         Rare
Infertility                           Unknown
Ovarian failure                       Unknown
Oligomenorrhea                        Unknown
Testicular atrophy                    Unknown
Blood estrogen decreased              Unknown
Blood gonadotropin increased          Unknown
Congenital, familial and   Intra-uterine death of the fetus      Unknown genetic disorders          Fetal malformation                    Unknown Fetal growth retardation              Unknown
Fetal toxicity (including             Unknown myelosuppression/gastroenteritis)
General disorders and      Fever                                 Very common administration site        Asthenia                              Common conditions                 Mucosal inflammation                  Common Chest pain                            Rare
Headache                              Very rare
Multi-organ failure                   Unknown
Edema                                 Unknown
Flu-like illness                      Unknown
General physical deterioration        Unknown
Injection/infusion site reactions10   Unknown

Adverse drug reactions
System organ class                      Side effect                       Frequency Investigations            Blood lactate dehydrogenase increased            Unknown C-reactive protein increased                     Unknown
1   including other bacterial, fungal, viral, protozoal, parasitic, reactivation of latent infections, including viral hepatitis, tuberculosis, JC virus with progressive multifocal leukoencephalopathy (including fatal outcomes), Pneumocystis jiroveci, herpes zoster, Strongyloides.
2 including fatal outcomes.

3 including acute myeloid leukemia and acute promyelocytic leukemia.

4        manifested as Bone marrow failure, Pancytopenia, Neutropenia, Agranulocytosis,
Granulocytopenia, Thrombocytopenia (complicated by bleeding), Leukopenia, Anemia 5 manifested as reversible posterior leukoencephalopathy syndrome, myelopathy,  peripheral neuropathy, polyneuropathy, neuralgia, dysesthesia, hypoesthesia, paresthesia, tremor, dysgeusia, hypogeusia, parosmia.
6 manifested as Atrial fibrillation, Supraventricular arrhythmia, Ventricular arrhythmia, 
Bradycardia, Tachycardia, Palpitation
7 manifested by pulmonary fibrosis, obliterative bronchiolitis, organizing pneumonia,  alveolitis allergic, pneumonitis.
8 Hepatic failure, Hepatic encephalopathy, Ascites, Hepatomegaly, Jaundice, Blood bilirubin  increased, Hepatic enzymes increased (ASAT, ALAT, ALP, gamma-GT)
9 persistent

10 manifested by thrombosis, necrosis, phlebitis, inflammation, pain, swelling, erythema.
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