Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Based on results from clinical trials including 1725 patients approximately 8 % of patients treated with Recormon are expected to experience adverse reactions.

Anaemic patients with chronic renal failure
The most frequent adverse reaction during treatment with Recormon is an increase in blood pressure or aggravation of existing hypertension, especially in cases of rapid PCV increase (see section 4.4). Hypertensive crisis with encephalopathy-like symptoms (e.g. headaches and confused state, sensorimotor disorders - such as speech disturbance or impaired gait - up to tonoclonic seizures) may also occur in individual patients with otherwise normal or low blood pressure (see section 4.4).

Shunt thromboses may occur, especially in patients who have a tendency to hypotension or whose arteriovenous fistulae exhibit complications (e.g. stenoses, aneurisms), see section 4.4. In most cases, a fall in serum ferritin values simultaneous with a rise in packed cell volume is observed (see section 4.4). In addition, transient increases in serum potassium and phosphate levels have been observed in isolated cases (see section 4.4).

In isolated cases, neutralising anti erythropoietin antibody-mediated pure red cell aplasia (PRCA) associated with Recormon therapy has been reported. In case anti-erythropoietin antibody-mediated PRCA is diagnosed, therapy with Recormon must be discontinued and patients should not be switched to another erythropoietic protein (see section 4.4).

Adverse reactions are listed in Table 1 below.

Patients with cancer
Epoetin beta treatment-related headache and hypertension which can be treated with drugs are common (see section 4.4).

In some patients, a fall in serum iron parameters is observed (see section 4.4).

Clinical studies have shown a higher frequency of thromboembolic events in cancer patients treated with Recormon compared to untreated controls or placebo. In patients treated with Recormon, this incidence is 7 % compared to 4 % in controls; this is not associated with any increase in thromboembolic mortality compared with controls.

Adverse reactions are listed in Table 2 below.

Patients in an autologous blood predonation programme
Patients in an autologous blood predonation programme have been reported to show a slightly higher frequency of thromboembolic events. However, a causal relationship with treatment with Recormon could not be established.

In placebo controlled trials temporary iron deficiency was more pronounced in patients treated with Recormon than in controls (see section 4.4).

Adverse reactions are listed in Table 3 below.

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment (see section 4.4)

Tabulated list of adverse reactions
Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: 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).



Table 1: Adverse reactions attributed to the treatment with Recormon in controlled clinical trials in CKD patients System organ class             Adverse reaction                Frequency Vascular disorders             Hypertension                    Common Hypertensive crisis             Uncommon
Nervous system disorders       Headache                        Common Blood and the lymphatic        Shunt thrombosis                Rare system disorders               Thrombocytosis                  Very rare 
Table 2:        Adverse reactions attributed to the treatment with Recormon in controlled clinical trials in cancer patients
System organ class            Adverse reaction                  Frequency Vascular disorders            Hypertension                     Common Blood and the lymphatic       Thromboembolic event             Common system disorders
Nervous system disorders      Headache                         Common 
Table 3:        Adverse reactions attributed to the treatment with Recormon in controlled clinical trials in patients in an autologous blood predonation programme

System organ class             Adverse reaction                  Frequency Nervous system disorders       Headache                          Common 
Description of selected adverse reactions
Rarely epoetin beta treatment-related skin reactions such as rash, pruritus, urticaria or injection site reactions may occur. In very rare cases epoetin beta treatment-related anaphylactoid reactions have been reported.
However, in controlled clinical studies no increased incidence of hypersensitivity reactions was found.
In very rare cases particularly when starting treatment, epoetin beta treatment-related flu-like symptoms such as fever, chills, headaches, pain in the limbs, malaise and/or bone pain have been reported. These reactions were mild or moderate in nature and subsided after a couple of hours or days.
Data from a controlled clinical trial with epoetin alfa or darbepoetin alfa, reported an incidence of stroke as common.

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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il