Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile
The most frequent adverse drug reaction during treatment with epoetin alfa is a dose- dependent increase in blood pressure or aggravation of existing hypertension.
Monitoring of the blood pressure should be performed, particularly at the start of therapy (see section 4.4: ”Special warnings and precautions for use”).

The most frequently occurring adverse drug reactions observed in clinical studies of epoetin alfa are diarrhoea, nausea, vomiting, pyrexia and headache. Influenza-like illness may occur especially at the start of treatment.

Respiratory tract congestion, which includes events of upper respiratory tract congestion, nasal congestion and nasopharyngitis, have been reported in studies with extended interval dosing in adult patients with renal insufficiency not yet undergoing dialysis.

An increased incidence of thrombotic vascular events (TVEs) has been observed in patients receiving ESAs (see section 4.4: ”Special warnings and precautions for use”).

Tabulated List of Adverse reactions

Of a total 3,417 subjects in 25 randomised, double-blinded, placebo or standard of care controlled studies, the overall safety profile of epoetin alfa was evaluated in 2,094 anaemic subjects. Included were 228 epoetin alfa-treated CRF subjects in 4 chronic renal failure studies (2 studies in pre-dialysis [N = 131 exposed CRF subjects] and 2 in dialysis [N = 97 exposed CRF subjects]; 1,404 exposed cancer subjects in 16 studies of anaemia due to chemotherapy; 147 exposed subjects in 2 studies for autologous blood donation; 213 exposed subjects in 1 study in the perisurgical period, and 102 exposed subjects in 2 MDS studies. Adverse drug reactions reported by ≥ 1% of subjects treated with epoetin alfa in these studies are shown in the table below.

Frequencies estimate 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), not known (cannot be estimated from the available data).
MedDRA System                Adverse Reaction              Frequency Organ Classification         (Preferred
(SOC)                        Term Level)
Blood and lymphatic          Pure red cell aplasia3,
Rare system disorders             Thrombocythaemia
Metabolism and
Hyperkalaemia1                Uncommon nutrition disorders
Immune system                Hypersensitivity3             Uncommon disorders                    Anaphylactic reaction3        Rare
Nervous system               Headache                      Common disorders                    Convulsion                    Uncommon
Hypertension, Venous
Common
Vascular disorders           and arterial thromboses2
Hypertensive crisis3          Not known
Respiratory, thoracic        Cough                         Common and mediastinal              Respiratory tract
Uncommon disorders                    congestion
Gastrointestinal             Diarrhoea, Nausea,
Very common disorders                    Vomiting
Rash                          Common
Skin and subcutaneous
Urticaria3                    Uncommon tissue disorders
Angioneurotic oedema3         Not known
Musculoskeletal and          Arthralgia, Bone pain,
connective tissue            Myalgia, Pain in              Common disorders                    extremity
Congenital, familial and
Porphyria acute3              Rare genetic disorders
Pyrexia                       Very common
Chills, Influenza like
General disorders and        illness, Injection site
Common administration site          reaction, Oedema conditions                   peripheral
Medicinal product
Not known ineffective3
Anti-erythropoietin
Investigations                                             Rare antibody positive
1
Common in dialysis
2
Includes arterial and venous, fatal and non fatal events, such as deep venous thrombosis, pulmonary emboli, retinal thrombosis, arterial thrombosis (including myocardial infarction), cerebrovascular accidents (including cerebral infarction and cerebral haemorrhage) transient ischaemic attacks, and shunt thrombosis (including dialysis equipment) and thrombosis within arteriovenous shunt aneurisms
3
Addressed in the subsection below and/or in section 4.4
Description of selected adverse reactions
Hypersensitivity reactions, including cases of rash (including urticaria), anaphylactic reactions, and angioneurotic oedema have been reported (see section 4.4: ”Special warnings and precautions for use”).

SCARs including SJS and TEN, which can be life-threatening or fatal, have been reported in association with epoetin treatment (see section 4.4).

Hypertensive crisis with encephalopathy and seizures, requiring the immediate attention of a physician and intensive medical care, have occurred also during epoetin alfa treatment in patients with previously normal or low blood pressure. Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning signal (see section 4.4: ”Special warnings and precautions for use”).

Antibody-mediated pure red cell aplasia has been very rarely reported in <1/10,000 cases per patient year after months to years of treatment with epoetin alfa (see section 4.4: ”Special warnings and precautions for use”). More cases have been reported with subcutaneous (SC) route of administration, compared with the IV route.


Paediatric population with chronic renal failure on haemodialysis

The exposure of paediatric patients with chronic renal failure on haemodialysis in clinical studies and post-marketing experience is limited. No paediatric-specific adverse reactions not mentioned previously in the table above, or any that were not consistent with the underlying disease were reported in this population.

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