Adverse reactions : תופעות לוואי

4.8   Undesirable effects

(a)     Summary of the safety profile
The safety data base from clinical trials comprised 3,042 CKD patients, including 1,939 patients treated with MIRCERA and 1,103 with another ESA. Approximately 6% of patients treated with MIRCERA are expected to experience adverse reactions. The most frequent reported adverse reaction was hypertension (common).

(b)     Tabulated list of adverse reactions
Adverse reactions in Table 2 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 2: Adverse reactions attributed to the treatment with MIRCERA in CKD patients Adverse reactions observed only during post-marketing are marked (*).

System organ class            Frequency                  Adverse reaction Blood and lymphatic           Uncommon                   Thrombocytopenia* system disorders              Not known                  Pure red cell aplasia* Rare                       Hypersensitivity
Immune system disorders
Not known                  Anaphylactic reaction*
Uncommon                   Headache
Nervous system disorders
Rare                       Hypertensive encephalopathy
Common                     Hypertension
Rare                       Hot flush
Vascular disorders
Uncommon                   Thrombosis*
Rare                       Pulmonary embolism*
Rare                       Rash, maculopapular
Skin and subcutaneous
Stevens-Johnson syndrome / disorders                     Not known toxic epidermal necrolysis*
Injury, poisoning and
Uncommon                   Vascular access thrombosis procedural complications

(c)     Description of selected adverse reactions
Cases of thrombocytopenia have been reported from post-marketing setting. A slight decrease in platelet counts remaining within the normal range was observed in clinical studies.
Platelet counts below 100 x 109/l were observed in 7% of patients treated with MIRCERA and 4% of patients treated with other ESAs during clinical development. In a post- authorisation safety study with long treatment exposure of up to 8.4 years, baseline platelet counts below 100 x 109/l was present in 2.1% of patients in the MIRCERA group and 2.4% of patients in other ESAs group. During the study, platelet counts below 100 x 109/l were observed yearly in 1.5% to 3.0% of patients treated with MIRCERA and 1.6% to 2.5% of patients treated with other ESAs.’

Data from a controlled clinical trial with epoetin alfa or darbepoetin alfa reported an incidence of stroke as common. A post-authorisation safety study showed similar incidence of stroke between MIRCERA (6.3%) and reference ESAs groups (epoetin alfa, darbepoetin alfa and epoetin beta) (7%).

As with other ESAs, cases of thrombosis, including pulmonary embolism, have been reported in the post-marketing setting (see section 4.4).

Neutralising anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been reported, frequency unknown. In case PRCA is diagnosed, therapy with MIRCERA must be discontinued, and patients should not be switched to another recombinant erythropoietic protein (see section 4.4).

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://sideeffects.health.gov.il