BESREMI SIDE EFFECTS
- Generic Name: ropeginterferon alfa-2b-njft
- Brand Name: BESREMi
SIDE EFFECTS
Clinical Trials Experience
The following clinically significant adverse reactions are described elsewhere in the labeling.
- Depression and Suicide
- Endocrine Toxicity
- Cardiovascular Toxicity
- Decreased Peripheral Blood Counts
- Hypersensitivity Reactions
- Pancreatitis
- Colitis
- Pulmonary Toxicity
- Ophthalmologic Toxicity
- Hyperlipidemia
- Hepatotoxicity
- Renal Toxicity
- Dental and Periodontal Toxicity
- Dermatologic Toxicity
- Driving and Operating Machinery
- Embryo-Fetal Toxicity
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the Warnings and Precautions section reflects exposure to BESREMi as monotherapy for the treatment of polycythemia vera dosed every two to four weeks in 178 patients in two open-label trials [PEGINVERA, PROUD/CONTINUATION PV]. The mean age at baseline was 58.6 years (range 30-85 years), 88 (49.4%) women, 90 (50.6%) men, 177 (99%) Caucasian and 1 (1%) Asian. Among 178 patients who received BESREMi, 80% were exposed for 12 months or longer. The mean dose of BESREMi was 334 mcg SD ± 121 during the treatment period. In this pooled safety population, the most common adverse reactions greater than 10%, were liver enzyme elevations (20%), leukopenia (20%), thrombocytopenia (19%), arthralgia (13%), fatigue (12%), myalgia (11%), and influenza-like illness (11%).
The safety findings described below reflect exposure to BESREMi as monotherapy for the treatment of polycythemia vera in 51 patients in the PEGINVERA study. Among the 51 patients receiving BESREMi, 71% were exposed for 12 months or longer, 63% were exposed for three years or longer, and 53% were exposed for greater than five years.
Serious adverse reactions were reported in 16% of patients in the PEGINVERA study. The most common serious adverse reactions observed during the study (> 4%) included urinary tract infection (8%), transient ischemic attack (6%) and depression (4%).
Adverse reactions requiring permanent discontinuation in >2% of patients who received BESREMi included depression (8%) arthralgia (4%), fatigue (4%), and general physical health deterioration (4%) In the PEGINVERA study, patients were not pre-screened for depression or anxiety disorders.
The most common adverse reactions reported in ≥10% of patients in the PEGINVERA study are listed in Table 2.
Table 1 : Adverse Reactions in > 10% of Subjects with Polycythemia Vera in the PEGINVERA Study Over 7.5 Years
| Adverse Reactions* | BESREMi N=51 % |
| Influenza-like illness a | 59 |
| Arthralgia | 47 |
| Fatigue b | 47 |
| Pruritis | 45 |
| Nasopharyngitis c | 43 |
| Musculoskeletal pain d | 41 |
| Headache e | 39 |
| Diarrhea | 33 |
| Hyperhidrosis f | 29 |
| Nausea | 28 |
| Upper respiratory tract infection g | 27 |
| Local administration site reactions | 26 |
| Dizziness | 22 |
| Abdominal pain h | 20 |
| Depression | 20 |
| Sleep disorder i | 20 |
| Leukopenia | 18 |
| Decreased appetite | 18 |
| Alopecia | 16 |
| Edema j | 16 |
| Hypertension k | 16 |
| Muscle spasms | 16 |
| Neutropenia | 16 |
| Rash l | 16 |
| Transaminase elevations m | 16 |
| Urinary tract infection | 16 |
| Thrombocytopenia | 12 |
| Vertigo | 12 |
| *Adverse Reactions defined as all treatment emergent adverse events Grouped Term Definitions a Includes pyrexia, chills, and influenza-like illness. b Includes asthenia, malaise, and fatigue. c Includes pharyngitis and nasopharyngitis. d Includes musculoskeletal pain, back pain, pain in extremity, bone pain, flank pain, and spinal pain. e Includes headache, migraine, and head pain. f Includes night sweats and hyperhidrosis. g Includes upper respiratory tract infection, rhinitis, bronchitis, and respiratory tract infection. h Includes abdominal pain upper, abdominal pain lower, and abdominal pain. i Includes insomnia, sleep disorder, and abnormal dreams. j Includes peripheral edema and generalized edema. k Includes hypertension and hypertensive crisis. l Includes rash, maculopapular rash, and pruritic rash. m Includes transaminase increase, hepatic enzyme increase, GGT increase, AST increase, and ALT increase. |
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Clinically relevant adverse reactions in < 10% of patients include:
Cardiovascular System: Atrial fibrillation
Immunogenicity
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 in the studies described below with the incidence of antibodies in other studies or to other interferon alfa-2b products may be misleading.
The incidence of binding antibodies to ropeginterferon alfa-2b-njft was 1.4% (2/146) and they were observed as early as 8 weeks post-dosing. Among the patients who tested positive for binding antibodies, none developed neutralizing antibodies.
SRC: NLM .