Adverse reactions : תופעות לוואי

Adverse reactions
MedDRA system           Very common         Common              Uncommon             Rare organ class      (≥ 1/10)            (≥ 1/100 to         (≥ 1/1,000 to        (≥ 1/10,000 to < 1/10)             < 1/100)             < 1/1,000)
Infections                           Sepsis and                                  Bronchitis
Infestations                         Upper respiratory tract infection
Urinary tract infection
Blood and        Thrombocytopenia    Splenomegalya       Leukocytosisa        Splenic rupturea lymphatic        Anaemia             Haemoglobin                              Sickle cell anaemia system                               decreasede                               with crisis disorders                                                                     Extramedullary haematopoiesis
Immune                                                   Hypersensitivity     Anaphylactic system                                                   Drug                 reaction disorders                                                Hypersensitivitya Graft versus Host
Diseaseb
Metabolism                           Decreased           Hyperuricaemia       Blood glucose and                                  appetitee           Blood uric acid      decreased nutrition                            Blood lactate       increased            Pseudogouta disorders                            dehydrogenase                            (Chondrocalcinosis increased                                Pyrophosphate)
Fluid volume disturbances
Psychiatic                           Insomnia diorders
Nervous          Headachea           Dizziness system                               Hypoaesthesia disorders                            Paraesthesia
Vascular                             Hypertension        Veno-occlusive       Capillary leak disorders                            Hypotension         diseased             syndromea Aortitis
Respiratory,                         Haemoptysis         Acute respiratory thoracic                             Dyspnoea            distress and                                  Cougha              syndromea mediastinal                          Oropharyngeal       Respiratory disorders                            paina,e             failurea
Epistaxis           Pulmonary oedemaa
Pulmonary haemorrhage
Interstitial lung diseasea
Lung infiltrationa
Hypoxia
Gastro-          Diarrhoeaa, e       Oral pain intestinal       Vomitinga,e         Constipatione disorders        Nauseaa


Hepato-                               Hepatomegaly         Aspartate biliary                               Blood alkaline       Amino- disorders                             phosphatase          transferase increased            increased
Gamma-glutamyl transferase increased
Skin and         Alopeciaa            Rasha                Rash maculo-          Cutaneous sub-                                  Erythema             papular               vasculitisa cutaneous                                                                        Sweets syndrome tissue                                                                           (acute febrile disorders                                                                        neutrophilic dermatosis)
Musculo-       Musculoskeletal        Muscle spasms        Osteoporosis         Bone density skeletal and painc                                                              decreased connective                                                                      Exacerbation of tissue                                                                          rheumatoid arthritis disorders
Renal and                             Dysuria              Proteinuria         Glomerulonephritis urinary                               Haematuria                               Urine abnormality disorders
General        Fatiguea               Chest paina          Injection site disorders      Mucosal                Paina                reaction a                 a and ad-        inflammation           Asthenia ministration Pyrexia                  Malaisee site                                  Oedema conditions                            peripherale
Injury,                               Transfusion poisoning                             reactione and procedural complicatio ns a
See section c (Description of selected adverse reactions) b
There have been reports of GvHD and fatalities in patients after allogeneic bone marrow transplantation (see section c) c
Includes bone pain, back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain, musculoskeletal chest pain, neck pain d
Cases were observed in the post-marketing setting in patients undergoing bone marrow transplant or PBPC mobilisation e
Adverse events with higher incidence in filgrastim patients compared to placebo and associated with the sequelae of the underlying malignancy or cytotoxic chemotherapy
 c. Description of selected adverse reactions

Hypersensitivity
Hypersensitivity-type reactions including anaphylaxis, rash, urticaria, angioedema, dyspnoea and hypotension occurring on initial or subsequent treatment have been reported in clinical studies and in post marketing experience. Overall, reports were more common after IV administration. In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship. Tevagrastim should be permanently discontinued in patients who experience a serious allergic reaction.

Pulmonary adverse events

In clinical studies and the post-marketing setting pulmonary adverse effects including interstitial lung 

disease, pulmonary oedema, and lung infiltration have been reported in some cases with an outcome of respiratory failure or acute respiratory distress syndrome (ARDS), which may be fatal (see section 4.4).

Splenomegaly and splenic rupture

Cases of splenomegaly and splenic rupture have been reported following administration of filgrastim.
Some cases of splenic rupture were fatal (see section 4.4).
Capillary leak syndrome

Cases of capillary leak syndrome have been reported with granulocyte colony-stimulating factor use.
These have generally occurred in patients with advanced malignant diseases, sepsis, taking multiple chemotherapy medications or undergoing apheresis (see section 4.4).

Cutaneous vasculitis

Cutaneous vasculitis has been reported in patients treated with filgrastim. The mechanism of vasculitis in patients receiving filgrastim is unknown. During long term use cutaneous vasculitis has been reported in 2% of SCN patients.

Leukocytosis
Leukocytosis (WBC > 50 x 109/l) was observed in 41% of normal donors and transient thrombocytopenia (platelets < 100 x 109/l) following filgrastim and leukapheresis was observed in 35% of donors (see section 4.4).

Sweets syndrome

Cases of Sweets syndrome (acute febrile neutrophilic dermatosis) have been reported in patients treated with filgrastim.

Pseudogout (chondrocalcinosis pyrophosphate)

Pseudogout (chondrocalcinosis pyrophosphate) has been reported in patients with cancer treated with filgrastim.

GvHD

There have been reports of GvHD and fatalities in patients receiving G CSF after allogeneic bone marrow transplantation (see sections 4.4 and 5.1).
 d. Paediatric population

Data from clinical studies in paediatric patients indicate that the safety and efficacy of filgrastim are similar in both adults and children receiving cytotoxic chemotherapy suggesting no age-related differences in the pharmacokinetics of filgrastim. The only consistently reported adverse event was musculoskeletal pain‚ which is no different from the experience in the adult population.

There is insufficient data to further evaluate filgrastim use in paediatric subjects.


e. Other special populations

Geriatric use
No overall differences in safety or effectiveness were observed between subjects over 65 years of age compared to younger adult (>18 years of age) subjects receiving cytotoxic chemotherapy and clinical experience has not identified differences in the responses between elderly and younger adult patients.

There is insufficient data to evaluate filgrastim use in geriatric subjects for other approved filgrastim indications.

Paediatric SCN patients

Cases of decreased bone density and osteoporosis have been reported in paediatric patients with SCN receiving chronic treatment with filgrastim.

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/