openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 2 · 5 matching rows.
adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: Neutrophil Engraftment Failure [see Warnings and Precautions (5.1) ] Delayed Platelet Engraftment [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] The most common Grade 3 or 4 non-laboratory adverse reactions (incidence ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and TDT, and decreased appetite in patients with SCD. ( 6 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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 most common Grade 3 or 4 non-laboratory adverse reactions (occurring in ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and patients with TDT, and decreased appetite in patients with SCD. All (100%) of the patients with TDT and SCD experienced Grade 3 or 4 neutropenia and thrombocytopenia. Other common Grade 3 or 4 laboratory abnormalities (≥ 50%) include leukopenia, anemia and lymphopenia. Sickle Cell Disease The safety of CASGEVY in patients with SCD was evaluated in an open-label, single-arm trial (Trial 1) and a long-term follow-up trial (Trial 3), in which 44 adolescent and adult patients with SCD were treated with CASGEVY after undergoing myeloablative conditioning with busulfan. The adverse event profile was generally consistent with that expected from busulfan myeloablative conditioning and HSC transplant. The median (min, max) duration of follow-up for 44 patients with SCD after being administered CASGEVY was 19.3 (0.8, 48.1) months. Serious adverse reactions after myeloablative conditioning and CASGEVY infusion were observed in 45% of patients with SCD. The most common serious adverse reactions (≥ 2 patients) were cholelithiasis, pneumonia, abdominal pain, constipation, pyrexia, abdominal pain upper, non-cardiac chest pain, oropharyngeal pain, pain, and sepsis. One (2%) patient died due to a COVID-19 infection and subsequent respiratory failure. The event was not related to CASGEVY. Table 1 presents the Grade 3 or 4 non-laboratory adverse reactions observed after myeloablative conditioning and CASGEVY infusion in at least 10% of patients in Trial 1. Table 2 presents the Grade 3 or 4 laboratory abnormalities that occurred in at least 10% of patients with SCD. Table 1: Grade 3 or 4 non-laboratory adverse reactions in ≥ 10% of patients with SCD who underwent busulfan myeloablative conditioning and received CASGEVY in Trial 1: Day 1 to Month 24 after CASGEVY infusion Table includes adverse events associated with busulfan myeloablative conditioning and treatment with CASGEVY. Adverse event profile generally consistent with that expected from busulfan myeloablative conditioning and HSC transplant. System organ class, preferred term Patients with SCD (Trial 1) (N=44) n (%) Blood and lymphatic system disorders Febrile neutropenia 21 (48) Gastrointestinal disorders Mucositis Mucositis includes mucosal inflammation, pharyngeal inflammation, and stomatitis. , Encompasses preferred terms that belong to other system organ class. 38 (86) Abdominal pain Abdominal pain includes abdominal pain and abdominal pain upper. 5 (11) Hepatobiliary disorders Cholelithiasis 5 (11) Metabolism and nutrition disorders Decreased appetite 18 (41) Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes back pain, musculoskeletal chest pain, neck pain, non-cardiac chest pain, and pain in extremity. , 6 (14) Skin and subcutaneous tissue disorders Pruritus 5 (11) Other clinically important adverse reactions that occurred in less than 10% of patients or were Grade 1 or Grade 2 include the following: Hepatobiliary disorders : Veno-occlusive liver disease (1 [2%] patient). Infusion-related reactions : 6 (14%) patients, including preferred terms of abdominal pain in 3 (7%) patients; and infusion-related reaction, nausea, non-cardiac chest pain, pruritus, sinus tachycardia, and vomiting in 1 (2%) patient each. Table 2: Grade 3 or 4 laboratory abnormalities in ≥ 10% of patients with SCD who underwent busulfan myeloablative conditioning and received CASGEVY in Trial 1: Day 1 to Month 24 after CASGEVY infusion Table includes laboratory abnormalities associated with busulfan myeloablative conditioning and treatment with CASGEVY. Laboratory abnormalities were generally consistent with those expected from busulfan myeloablative conditioning and HSC transplant. Laboratory abnormality Patients with SCD (Trial 1) N=44 The denominator for CD4 lymphocytes decreased is 43 and the denominator for all other laboratory data is 44, based on evaluable data at the time of the interim analysis. (%) Neutropenia 100 Thrombocytopenia 100 Leukopenia 98 Anemia 84 Lymphopenia 50 CD4 lymphocytes decreased 23 Activated partial thromboplastin time prolonged 16 Hyperbilirubinemia 14 Platelet engraftment Platelet engraftment in patients with SCD is defined as 3 consecutive measurements of platelet counts ≥ 50 × 10 9 /L, obtained on 3 different days after CASGEVY infusion, without administration of platelet transfusions for 7 days. In Trial 1, the median (min, max) time to platelet engraftment was 35 (23, 126) days (n=43). There was no association observed between bleeding events and time to platelet engraftment. Neutrophil engraftment Neutrophil engraftment is defined as 3 consecutive measurements of ANC ≥ 500 cells/µL on 3 different days after CASGEVY infusion, without use of the unmodified rescue CD34 + cells. In Trial 1, the median (min, max) time to neutrophil engraftment was 27 (15, 40) days (n=44). There was no association observed between infections and time to neutrophil engraftment. There was no use of rescue CD34 + cells in any patient. Transfusion-dependent β-thalassemia The safety of CASGEVY in patients with TDT was evaluated in an open-label, single-arm trial (Trial 2) and a long-term follow-up trial (Trial 3), in which 52 adolescent and adult patients with TDT were treated with CASGEVY after undergoing myeloablative conditioning with busulfan. The adverse event profile was generally consistent with that expected from busulfan myeloablative conditioning and HSC transplant. The median (min, max) duration of follow-up for 52 patients with TDT after being administered CASGEVY was 20.4 (2.1, 48.1) months. Serious adverse reactions after myeloablative conditioning and CASGEVY infusion were observed in 33% of patients with TDT. The most common serious adverse reactions (≥ 2 patients) were veno-occlusive liver disease, pneumonia, hypoxia, thrombocytopenia, viral infection, and upper respiratory tract infection. Table 3 presents the Grade 3 or 4 non-laboratory adverse reactions observed after myeloablative conditioning and CASGEVY infusion in at least 10% of patients in Trial 2. Table 4 presents the Grade 3 or 4 laboratory abnormalities that occurred in at least 10% of patients with TDT. Table 3: Grade 3 or 4 non-laboratory adverse reactions in ≥ 10% of patients with TDT who underwent busulfan myeloablative conditioning and received CASGEVY in Trial 2: Day 1 to Month 24 after CASGEVY infusion Table includes adverse events associated with busulfan myeloablative conditioning and treatment with CASGEVY. Adverse event profile generally consistent with that expected from busulfan myeloablative conditioning and HSC transplant. System organ class, preferred term Patients with TDT (Trial 2) (N=52) n (%) Blood and lymphatic system disorders Febrile neutropenia 28 (54) Gastrointestinal disorders Mucositis Mucositis includes anal inflammation, mucosal inflammation, pharyngeal inflammation, and stomatitis. , Encompasses preferred terms that belong to other system organ class. 37 (71) Hepatobiliary disorders Veno-occlusive liver disease 5 (10) Metabolism and nutrition disorders Decreased appetite 12 (23) Respiratory, thoracic and mediastinal disorders Epistaxis 7 (13) Other clinically important adverse reactions that occurred in less than 10% of patients or were Grade 1 or Grade 2 include the following: Immune system disorders : Hemophagocytic lymphohistiocytosis (1 [2%] patient). Nervous system disorders: Cerebellar hemorrhage (intracranial hemorrhage) (1 [2%] patient). Infusion-related reactions: 12 (23%) patients, including preferred terms of abdominal pain and nausea in 4 (8%) patients each; pruritus and vomiting in 2 (4%) patients each; and abdominal pain lower, chills, sinus tachycardia, and tachycardia in 1 (2%) patient each. Table 4: Grade 3 or 4 laboratory abnormalities in ≥ 10% of patients with TDT who underwent busulfan myeloablative conditioning and received CASGEVY in Trial 2: Day 1 to Month 24 after CASGEVY infusion Table includes laboratory abnormalities associated with busulfan myeloablative conditioning and treatment with CASGEVY. Laboratory abnormalities were generally consistent with those expected from busulfan myeloablative conditioning and HSC transplant. Laboratory abnormality Patients with TDT (Trial 2) N=52 The denominator for CD4 lymphocytes decreased is 48 and the denominator for all other laboratory data is 52, based on evaluable data at the time of the interim analysis. (%) Neutropenia 100 Thrombocytopenia 100 Leukopenia 98 Anemia 92 Lymphopenia 79 CD4 lymphocytes decreased 23 Hyperbilirubinemia 23 Alanine aminotransferase increased 19 Hypokalemia 19 Gamma-glutamyltransferase increased 17 Activated partial thromboplastin time prolonged 13 Hypocalcemia 12 Platelet engraftment Platelet engraftment in patients with TDT is defined as 3 consecutive measurements of platelet counts ≥ 20 × 10 9 /L, obtained on 3 different days after CASGEVY infusion, without administration of platelet transfusions for 7 days. In Trial 2, the median (min, max) time to platelet engraftment was 44 (20, 200) days (n=52). There is an increased risk of bleeding until platelet engraftment is achieved. In the clinical trials, there was no association observed between incidence of bleeding events and time to platelet engraftment. Patients without a spleen had an earlier median time to platelet engraftment than patients with an intact spleen. Median (min, max) time to platelet engraftment was 34.5 (20, 78) days in patients without a spleen and 47.5 (27, 200) days in patients with an intact spleen. While the use of thrombopoietin (TPO) mimetics was not specified in the trial protocol, five patients (10%) received a TPO mimetic at the time of platelet engraftment. All 5 patients continued TPO mimetic use for thrombocytopenia beyond engraftment. The total duration of TPO mimetic use was 98-457 days. Neutrophil engraftment Neutrophil engraftment is defined as 3 consecutive measurements of absolute neutrophil count (ANC) ≥ 500 cells/µL on 3 different days after CASGEVY infusion, without use of the unmodified rescue CD34 + cells. In Trial 2, the median (min, max) time to neutrophil engraftment was 29 (12, 56) days (n=52). There was no association observed between infections and time to neutrophil engraftment. One patient had neutrophil engraftment on Day 56. There was no use of rescue CD34 + cells in any patient.
adverse reactions table
<table width="85%" ID="table1"><caption>Table 1: Grade 3 or 4 non-laboratory adverse reactions in ≥ 10% of patients with SCD who underwent busulfan myeloablative conditioning and received CASGEVY in Trial 1: Day 1 to Month 24 after CASGEVY infusion <footnote ID="K1315">Table includes adverse events associated with busulfan myeloablative conditioning and treatment with CASGEVY. Adverse event profile generally consistent with that expected from busulfan myeloablative conditioning and HSC transplant.</footnote></caption><col width="55%" align="left" valign="middle"/><col width="45%" align="center" valign="middle"/><thead><tr><th align="center" styleCode="Lrule Rrule">System organ class, preferred term</th><th styleCode="Rrule">Patients with SCD (Trial 1) (N=44) n (%) </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Blood and lymphatic system disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Febrile neutropenia</td><td styleCode="Rrule">21 (48)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Mucositis <footnote ID="K1370">Mucositis includes mucosal inflammation, pharyngeal inflammation, and stomatitis.</footnote><sup>,</sup><footnote ID="t1f1">Encompasses preferred terms that belong to other system organ class.</footnote></td><td styleCode="Rrule">38 (86)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Abdominal pain <footnote ID="K1385">Abdominal pain includes abdominal pain and abdominal pain upper.</footnote></td><td styleCode="Rrule">5 (11)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Hepatobiliary disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Cholelithiasis</td><td styleCode="Rrule">5 (11)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Metabolism and nutrition disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased appetite</td><td styleCode="Rrule">18 (41)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Musculoskeletal pain <footnote ID="K1438">Musculoskeletal pain includes back pain, musculoskeletal chest pain, neck pain, non-cardiac chest pain, and pain in extremity.</footnote><sup>,</sup><footnoteRef IDREF="t1f1"/></td><td styleCode="Rrule">6 (14)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Pruritus</td><td styleCode="Rrule">5 (11)</td></tr></tbody></table>