Among the serious adverse reactions occurring during MIRCERA® treatment belong:
- Increased mortality, myocardial infarction, stroke, and thromboembolism
- Increased mortality and/or tumor progression in patients with cancer
- Pure red cell aplasia (PRCA)
- Serious allergic reactions
- Severe cutaneous reactions
Adverse Reactions in Clinical Trials in Adult Patients
In clinical trials, 2737 adult patients were exposed to MIRCERA®, including 1451 exposed for 6 months and 1144 exposed for greater than one year. MIRCERA® was studied primarily in active-controlled studies (n = 1789 received MIRCERA®, n = 948 received another ESA) and in long-term follow-up studies.
In the controlled trials, the rates of serious adverse reactions did not significantly differ between patients receiving MIRCERA® and another ESA (38% vs 42%), except for the occurrence of serious gastrointestinal hemorrhage (1.2% vs 0.2%). Adverse reaction rates did not importantly differ between patients receiving MIRCERA® or another ESA.
The most commonly reported adverse reactions in ≥ 10% of patients were hypertension, diarrhea, and nasopharyngitis. The most common adverse reactions that led to treatment discontinuation in the MIRCERA® clinical studies were hypertension, coronary artery disease, anemia, concomitant termination of other CKD therapy, and septic shock.
Adverse Reactions Occurring in ≥ 5% of Adult Patients with CKD
Adverse Reactions in Clinical Trials in Pediatric Patients
- In an open-label, multiple dose study, 64 pediatric patients (ages 5 to 17 years) with CKD who were on hemodialysis and who had stable hemoglobin levels while previously receiving another ESA (epoetin alfa/beta or darbepoetin alfa) were then converted to MIRCERA® administered intravenously once every 4 weeks for 20 weeks (core study period).
- Patients who completed the core study period with hemoglobin within ± 1 g/dL of their baseline hemoglobin and within the target range of 10 to 12 g/dL were eligible to enter an optional 52-week safety extension period (total duration of treatment, up to 73 weeks).
- In the extension period, 25 (out of 37) patients were treated for at least an additional 5 months.
- During the whole study (core study and safety extension), 33 patients were exposed to MIRCERA® for at least 6 months and 19 were exposed for greater than 15 months.
- The adverse reaction profile observed in pediatric patients was consistent with the safety profile found in adults.
- The efficacy and safety of MIRCERA® have not been established in patients less than 5 years of age.
All reported adverse reactions regardless of causality (more than 5% incidence) in the pediatric population included headache (22%), nasopharyngitis (22%), hypertension (19%), vomiting (11%), bronchitis (9%), abdominal pain (8%), arteriovenous fistula thrombosis (6%), cough (6%), device related infection (6%), hyperkalemia (6%), pharyngitis (6%), pyrexia (6%), thrombocytopenia (6%), and thrombosis in device (6%).
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to MIRCERA® in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
Neutralizing antibodies to MIRCERA® that cross-react with endogenous erythropoietin (EPO) and other ESAs can result in PRCA or severe anemia (with or without other cytopenias). Compared to subcutaneous administration, the intravenous route of administration may lessen the risk for development of antibodies to MIRCERA®.
In 1789 patients treated with MIRCERA® in clinical studies, antibody testing using an enzyme-linked immunosorbent assay (ELISA) was conducted at baseline and during treatment. Antibody development was not detected in any of the patients.
The following adverse reactions have been identified during post-approval use of MIRCERA®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has been reported.
Pure Red Cell Aplasia (PRCA)
Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to EPO, have been reported in patients treated with MIRCERA®.
MIRCERA® is contraindicated in patients with:
- Uncontrolled hypertension
- PRCA that begins after treatment with MIRCERA® or other EPO protein drugs
- History of serious or severe allergic reactions to MIRCERA® (e.g., anaphylactic reactions, angioedema, bronchospasm, pruritus, skin rash, urticaria)
For more information, please see the full Prescribing Information, including Boxed WARNING, and Medication Guide (English, Español) for MIRCERA®.
1MIRCERA® [prescribing information]. St. Gallen, Switzerland: Vifor (International) Inc.; June 2018.