Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The most frequently reported adverse reactions were bone pain (very common [≥ 1/10]) and musculoskeletal pain (common [≥ 1/100 to < 1/10]). Bone pain was generally of mild to moderate severity, transient and could be controlled in most patients with standard analgesics.

Hypersensitivity-type reactions, including skin rash, urticaria, angioedema, dyspnea, erythema, flushing, and hypotension occurred on initial or subsequent treatment with pegfilgrastim (uncommon [≥ 1/1,000 to < 1/100]). Serious allergic reactions, including anaphylaxis can occur in patients receiving pegfilgrastim (uncommon) (see section 4.4).

Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported as uncommon (≥ 1/1,000 to < 1/100) in cancer patients undergoing chemotherapy following administration of G-CSFs; see section 4.4 and section “Description of selected adverse reactions” below.

Splenomegaly, generally asymptomatic, is uncommon.

Splenic rupture including some fatal cases is uncommonly reported following administration of pegfilgrastim (see section 4.4).

Uncommon pulmonary adverse reactions including interstitial pneumonia, pulmonary edema, pulmonary infiltrates and pulmonary fibrosis have been reported. Uncommonly, cases have resulted in respiratory failure or ARDS, which may be fatal (see section 4.4).

Isolated cases of sickle cell crises have been reported in patients with sickle cell trait or sickle cell disease (uncommon in sickle cell patients) (see section 4.4).

Tabulated list of adverse reactions

The data in the table below describe adverse reactions reported from clinical trials and spontaneous reporting. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

MedDRA system                                             Adverse reactions organ class           Very common          Common                 Uncommon                      Rare (≥ 1/10)      (≥ 1/100 to < 1/10)   (≥ 1/1,000 to < 1/100)    (≥ 1/10,000 to < 1/1,000) Neoplasms benign,                                          Myelodysplastic malignant                                                  syndrome1 and unspecified                                            Acute myeloid leukemia1 (incl cysts and polyps)
Blood and                             Thrombocytopenia1; Sickle cell anemia lymphatic system                      Leukocytosis1      with crisis2; disorders                                                Splenomegaly2; Splenic rupture2
Immune system                                            Hypersensitivity disorders                                                reactions;
Anaphylaxis


Metabolism and                                                         Elevations in uric acid nutrition disorders

Nervous system             Headache1 disorders

Vascular disorders                                                     Capillary leak syndrome1 Aortitis 

Respiratory,                                                           Acute Respiratory            Pulmonary hemorrhage thoracic and                                                           Distress Syndrome2; mediastinal                                                            Pulmonary adverse disorders                                                              reactions (interstitial pneumonia, pulmonary edema, pulmonary infiltrates and pulmonary fibrosis);
Hemoptysis
Gastrointestinal    Nausea1 disorders
Skin and                                                               Sweet’s syndrome            Stevens-Johnson syndrome subcutaneous tissue                                                    (acute febrile neutrophilic disorders                                                              dermatosis)1,2; Cutaneous vasculitis1, 2

Musculoskeletal and Bone pain                Musculoskeletal pain connective tissue                            (myalgia, arthralgia,
disorders                                    pain in extremity,
back pain,
musculoskeletal pain,
neck pain)
Renal and urinary                                                      Glomerulonephritis2 disorders
General disorders                            Injection site pain1;     Injection site reactions2 and administrative                           Non-cardiac chest site conditions                              pain

Investigations                                                         Elevations in lactate dehydrogenase and alkaline phosphatase1;
Transient elevations in
LFT's for ALT or
AST1
1   See section “Description of selected adverse reactions” below.
2   This adverse reaction was identified through post-marketing surveillance but not observed in randomized, controlled clinical trials in adults. The frequency category was estimated from a statistical calculation based upon 1,576 patients receiving pegfilgrastim in nine randomized clinical trials.

Description of selected adverse reactions

Uncommon cases of Sweet’s syndrome have been reported, although in some cases underlying hematological malignancies may play a role.

Uncommon events of cutaneous vasculitis have been reported in patients treated with pegfilgrastim. The mechanism of vasculitis in patients receiving pegfilgrastim is unknown.


Injection site reactions, including injection site erythema (uncommon) as well as injection site pain (common) have occurred on initial or subsequent treatment with pegfilgrastim.

Common cases of leukocytosis (White Blood Count [WBC] > 100 × 109/L) have been reported (see section 4.4).

Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associated clinical effects, were uncommon; reversible, mild to moderate elevations in lactate dehydrogenase, with no associated clinical effects, were uncommon in patients receiving pegfilgrastim following cytotoxic chemotherapy.

Nausea and headaches were very commonly observed in patients receiving chemotherapy.

Uncommon elevations in liver function tests (LFTs) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), have been observed in patients after receiving pegfilgrastim following cytotoxic chemotherapy. These elevations are transient and return to baseline.

An increased risk of MDS/AML following treatment with pegfilgrastim in conjunction with chemotherapy and/or radiotherapy has been observed in an epidemiological study in breast and lung cancer patients (see section 4.4).

Common cases of thrombocytopenia have been reported.

Cases of capillary leak syndrome have been reported in the post-marketing setting with G-CSF use. These have generally occurred in patients with advanced malignant diseases, sepsis, taking multiple chemotherapy medications or undergoing apheresis (see section 4.4).

Pediatric population

The experience in children is limited. A higher frequency of serious adverse reactions in younger children aged 0-5 years (92%) has been observed compared to older children aged 6-11 and 12-21 years respectively (80% and 67%) and adults. The most common adverse reaction reported was bone pain (see sections 5.1 and 5.2).

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/ Additionally, you can report to Unipharm Ltd. via the following address: https://unipharm.co.il/