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The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of tolvaptan (Jinarc, Otuska) to slow progression of cyst developmen"...
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
- Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism [see WARNINGS AND PRECAUTIONS]
- Increased mortality and/or tumor progression in patients with cancer [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Pure red cell aplasia [see WARNINGS AND PRECAUTIONS]
- Serious allergic reactions [see WARNINGS AND PRECAUTIONS]
The most commonly reported adverse reactions in > 10% of patients were hypertension [see WARNINGS AND PRECAUTIONS], 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.
Clinical Trials Experience
The data described below reflect exposure to Mircera in 2737 patients, 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, and n=948 received another ESA) and in long-term follow up studies. The population was 18 to 92 years of age, 58% male, and the percentage of Caucasian, Black (including African Americans), Asian and Hispanic patients were 73%, 20%, 5%, and 9%, respectively. Approximately 85% of the patients were receiving dialysis. Most patients received Mircera using dosing regimens of once every two or four weeks, administered SC or IV.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of Mircera cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
Some of the adverse reactions reported are typically associated with CKD, or recognized complications of dialysis, and may not necessarily be attributable to Mircera therapy. Adverse reaction rates did not importantly differ between patients receiving Mircera or another ESA.
Table 4 summarizes the most frequent adverse reactions ( ≥ 5%) in patients treated with Mircera.
Table 4 : Adverse Reactions Occurring in ≥ 5% of
|Adverse Reaction||Patients Treated with Mircera (n=1789)|
|INFECTIONS AND INFESTATIONS|
|Upper Respiratory Tract Infection||9%|
|Urinary Tract Infection||5%|
|MUSCULOSKELETAL AND CONNECTIVE TISSUE|
|Pain in Extremity||5%|
|INJURY, POISONING AND PROCEDURAL COMPLICATIONS|
|Arteriovenous Fistula Thrombosis||5%|
|Arteriovenous Fistula Site Complication||5%|
|METABOLISM AND NUTRITION|
|RESPIRATORY, THORACIC AND MEDIASTINAL|
In the controlled trials, the rates of serious adverse reactions did not importantly differ between patients receiving Mircera and another ESA (38% vs. 42%) except for the occurrence of serious gastrointestinal hemorrhage (1.2% vs. 0.2%). Serious hemorrhagic adverse reactions of all types occurred among 5% and 4% of patients receiving Mircera or another ESA, respectively.
As with all therapeutic proteins, there is a potential for immunogenicity. Neutralizing antibodies to Mircera that cross-react with endogenous erythropoietin and other ESAs can result in PRCA or severe anemia (with or without other cytopenias) [see WARNINGS AND PRECAUTIONS]. Compared to SC administration, the IV 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 incidence 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 with the incidence of antibodies to other ESAs may be misleading.
Read the Mircera (methoxy polyethylene glycol-epoetin beta) Side Effects Center for a complete guide to possible side effects
No formal drug/drug interaction studies have been performed.
Last reviewed on RxList: 10/16/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Mircera Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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