【medical-news】FDA修改克罗拉滨、美托咪啶、苯达莫司汀安全标签
发布于 2009-01-05 · 浏览 2209 · IP 浙江浙江
这个帖子发布于 16 年零 119 天前，其中的信息可能已发生改变或有所发展。
FDA Safety Changes: Clolar, Precedex, Treanda
http://www.medscape.com/viewarticle/586214
January 2, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions for clofarabine injection, dexmedetomidine HCl injection, and bendamustine HCl injection.
Clofarabine (Clolar) Linked to Increased Risk for Infection, Fetal Harm During Pregnancy
On October 17, 2008, the FDA approved safety labeling revisions for the purine nucleoside metabolic inhibitor clofarabine (Clolar injection for intravenous use; Genzyme Corp) to provide new or updated information regarding monitoring of complete blood and platelet counts, an increased risk for infection, monitoring for tumor lysis syndrome and cytokine release, observed elevations in hepatobiliary enzyme levels, potential risk for hepatotoxicity in patients who have undergone hematopoietic stem-cell transplantation, and potential fetal harm during pregnancy.
Clofarabine injection is indicated for the treatment of pediatric patients (ages 1 - 21 years) with relapsed or refractory acute lymphoblastic leukemia after at least 2 previous regimens.
Additional language was included under all warnings and precautions. Hematologic toxicity now includes a statement to monitor blood counts and platelet counts during therapy with clofarabine intravenous injection. Patients with infections should be monitored for signs and symptoms of infection and treated promptly.
For hyperuricemia (tumor lysis syndrome), clinicians are instructed to provide intravenous infusion fluids throughout the 5 days of clofarabine treatment to reduce the effects of tumor lysis syndrome and other adverse events and to administer allopurinol if hyperuricemia is expected.
Clinicians are also instructed to reinstitute clofarabine treatment at a 25% dose reduction for patients regaining stability after systemic inflammatory response syndrome or capillary leak syndrome and organ dysfunction, and the use of a prophylactic steroid to prevent signs and symptoms of cytokine release is suggested. Data regarding elevations in hepatobiliary enzyme levels are now addressed in the section on adverse reactions.
For hepatic and renal impairment, a potential increased risk for hepatotoxicity suggestive of veno-occlusive disease after clofarabine administration (40 mg/m2) when used in combination with etoposide (100 mg/m2) and cyclophosphamide (440 mg/m2) is noted for patients who have previously undergone hematopoietic stem-cell transplantation. Severe hepatotoxic events are also noted for an ongoing phase 1/2 combination study in pediatric patients with relapsed or refractory acute leukemia.
Clofarabine may also cause fetal harm when administered to a pregnant woman, according to the updated label.
For adverse reactions, data have been updated to include the most commonly reported (≥ 5% overall) adverse events by organ system class (N = 115; pooled analysis). The least common adverse reactions in 1% to 4% of patients with acute lymphoblastic leukemia or acute myelogenous leukemia were added, including cecitis and pancreatitis; hyperbilirubinemia; hypersensitivity; bacterial infection; bacteremia; fungal infection; sepsis; virus infection; pneumonia; sinusitis; increased blood creatinine levels; mental status change; and pulmonary edema.
The incidence of treatment-emergent laboratory abnormalities after clofarabine administration may occur; the abnormalities occurring in more than half of patients at grade 3 or higher are leukopenia (87.7%), lymphopenia (82.3%), thrombocytopenia (79.8%), anemia (75.4%), and neutropenia (63.7%).
Adverse reactions noted from postmarketing experience include bone marrow failures, serious hepatotoxic adverse reactions of veno-occlusive disease in adult patients after hematopoietic stem-cell transplantation, and occurrences of Stevens-Johnson syndrome and toxic epidermal necrolysis in patients treated with concomitant medications (allopurinol or antibiotics).
The safety and effectiveness of clofarabine have not been established in geriatric patients 65 years and older.
Dexmedetomidine HCl (Precedex) Adds Counseling Information, New Data for Procedural Sedation
On October 17, 2008, the FDA approved safety labeling revisions for dexmedetomidine HCl (Precedex injection; Hospira, Inc) to include counseling information and data for procedural sedation, carcinogenesis, mutagenesis, and impairment of fertility.
Dexmedetomidine is a relatively selective alpha2-adrenergic agonist indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive-care setting and sedation of nonintubated patients before and/or during surgical and other procedures.
According to patient counseling information, patients who receive an infusion for more than 6 hours should be informed to report nervousness, agitation, and headaches that may occur for up to 48 hours or symptoms that may occur within 48 hours such as weakness, confusion, excessive sweating, weight loss, abdominal pain, salt cravings, diarrhea, constipation, dizziness, or lightheadedness.
The section for warnings and precautions has been amended to note that withdrawal symptoms were not seen after discontinuation of short-term (< 6 hours) infusions of dexmedetomidine. Data regarding adverse reactions during procedural sedation were derived from 2 trials in 318 adult patients, for which hypotension (54%), bradycardia (14%), and dry mouth (3%) were the most common adverse reactions.
Data regarding the use of dexmedetomidine for procedural sedation in geriatric patients indicated that hypotension occurred at a higher incidence in patients 65 years or older (72%) and in those 75 years or older (74%) vs patients younger than 65 years. For patients older than 65 years, a recommendation was added for a reduced loading dose of 0.5 µg/kg given for 10 minutes and a reduction in the maintenance infusion.
Bendamustine (Treanda) Receives Additional Warnings and Precautions
On October 31, 2008, the FDA approved safety labeling revisions for bendamustine (Treanda; Cephalon, Inc) for injection, an alkylating drug indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin's lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.
Safety changes for warnings and precautions included data for myelosuppression from 2 studies in which 98% of patients had grade 3 to 4 myelosuppression, and 2% of patients died of myelosuppression-related adverse reactions (neutropenic sepsis, diffuse alveolar hemorrhage with grade 3 thrombocytopenia, pneumonia from opportunistic infection).
Data regarding skin reactions were added to warnings and precautions, for which 1 case of toxic epidermal necrolysis occurred in a study of bendamustine (90 mg/m2) in combination with rituximab. Toxic epidermal necrolysis has been reported for rituximab, but the relationship of toxic epidermal necrolysis to bendamustine has not been determined.
Other malignant neoplasms were added to warnings and precautions, noting reports of premalignant and malignant diseases that developed in patients treated with bendamustine. The link of bendamustine with these diseases has not been determined. Conditions included myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma.
For adverse reactions, data have been updated to include nonhematologic adverse reactions occurring in 5% or more of patients with NHL treated with bendamustine by organ system class (N = 176). Common adverse reactions by organ system class included nausea (75%, gastrointestinal tract), fatigue (57%, general), anorexia (23%, metabolism and nutrition), cough (22%, respiratory tract), headache (21%, nervous system), and rash (16%, skin and subcutaneous tissue). Hematologic laboratory abnormalities were also added: patients with grade 3 to 4 disease had decreased levels of lymphocytes (94%), leukocytes (56%), hemoglobin (11%), neutrophils (60%), and platelets (25%). The most common serious adverse reactions included febrile neutropenia and pneumonia.
Information added to address specific patient populations included similar efficacy between geriatric patients (> age 65 years) and younger patients (< age 65 years) and no difference in efficacy between the sexes. Both of these patient populations were included in CLL and NHL studies
http://www.medscape.com/viewarticle/586214
January 2, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions for clofarabine injection, dexmedetomidine HCl injection, and bendamustine HCl injection.
Clofarabine (Clolar) Linked to Increased Risk for Infection, Fetal Harm During Pregnancy
On October 17, 2008, the FDA approved safety labeling revisions for the purine nucleoside metabolic inhibitor clofarabine (Clolar injection for intravenous use; Genzyme Corp) to provide new or updated information regarding monitoring of complete blood and platelet counts, an increased risk for infection, monitoring for tumor lysis syndrome and cytokine release, observed elevations in hepatobiliary enzyme levels, potential risk for hepatotoxicity in patients who have undergone hematopoietic stem-cell transplantation, and potential fetal harm during pregnancy.
Clofarabine injection is indicated for the treatment of pediatric patients (ages 1 - 21 years) with relapsed or refractory acute lymphoblastic leukemia after at least 2 previous regimens.
Additional language was included under all warnings and precautions. Hematologic toxicity now includes a statement to monitor blood counts and platelet counts during therapy with clofarabine intravenous injection. Patients with infections should be monitored for signs and symptoms of infection and treated promptly.
For hyperuricemia (tumor lysis syndrome), clinicians are instructed to provide intravenous infusion fluids throughout the 5 days of clofarabine treatment to reduce the effects of tumor lysis syndrome and other adverse events and to administer allopurinol if hyperuricemia is expected.
Clinicians are also instructed to reinstitute clofarabine treatment at a 25% dose reduction for patients regaining stability after systemic inflammatory response syndrome or capillary leak syndrome and organ dysfunction, and the use of a prophylactic steroid to prevent signs and symptoms of cytokine release is suggested. Data regarding elevations in hepatobiliary enzyme levels are now addressed in the section on adverse reactions.
For hepatic and renal impairment, a potential increased risk for hepatotoxicity suggestive of veno-occlusive disease after clofarabine administration (40 mg/m2) when used in combination with etoposide (100 mg/m2) and cyclophosphamide (440 mg/m2) is noted for patients who have previously undergone hematopoietic stem-cell transplantation. Severe hepatotoxic events are also noted for an ongoing phase 1/2 combination study in pediatric patients with relapsed or refractory acute leukemia.
Clofarabine may also cause fetal harm when administered to a pregnant woman, according to the updated label.
For adverse reactions, data have been updated to include the most commonly reported (≥ 5% overall) adverse events by organ system class (N = 115; pooled analysis). The least common adverse reactions in 1% to 4% of patients with acute lymphoblastic leukemia or acute myelogenous leukemia were added, including cecitis and pancreatitis; hyperbilirubinemia; hypersensitivity; bacterial infection; bacteremia; fungal infection; sepsis; virus infection; pneumonia; sinusitis; increased blood creatinine levels; mental status change; and pulmonary edema.
The incidence of treatment-emergent laboratory abnormalities after clofarabine administration may occur; the abnormalities occurring in more than half of patients at grade 3 or higher are leukopenia (87.7%), lymphopenia (82.3%), thrombocytopenia (79.8%), anemia (75.4%), and neutropenia (63.7%).
Adverse reactions noted from postmarketing experience include bone marrow failures, serious hepatotoxic adverse reactions of veno-occlusive disease in adult patients after hematopoietic stem-cell transplantation, and occurrences of Stevens-Johnson syndrome and toxic epidermal necrolysis in patients treated with concomitant medications (allopurinol or antibiotics).
The safety and effectiveness of clofarabine have not been established in geriatric patients 65 years and older.
Dexmedetomidine HCl (Precedex) Adds Counseling Information, New Data for Procedural Sedation
On October 17, 2008, the FDA approved safety labeling revisions for dexmedetomidine HCl (Precedex injection; Hospira, Inc) to include counseling information and data for procedural sedation, carcinogenesis, mutagenesis, and impairment of fertility.
Dexmedetomidine is a relatively selective alpha2-adrenergic agonist indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive-care setting and sedation of nonintubated patients before and/or during surgical and other procedures.
According to patient counseling information, patients who receive an infusion for more than 6 hours should be informed to report nervousness, agitation, and headaches that may occur for up to 48 hours or symptoms that may occur within 48 hours such as weakness, confusion, excessive sweating, weight loss, abdominal pain, salt cravings, diarrhea, constipation, dizziness, or lightheadedness.
The section for warnings and precautions has been amended to note that withdrawal symptoms were not seen after discontinuation of short-term (< 6 hours) infusions of dexmedetomidine. Data regarding adverse reactions during procedural sedation were derived from 2 trials in 318 adult patients, for which hypotension (54%), bradycardia (14%), and dry mouth (3%) were the most common adverse reactions.
Data regarding the use of dexmedetomidine for procedural sedation in geriatric patients indicated that hypotension occurred at a higher incidence in patients 65 years or older (72%) and in those 75 years or older (74%) vs patients younger than 65 years. For patients older than 65 years, a recommendation was added for a reduced loading dose of 0.5 µg/kg given for 10 minutes and a reduction in the maintenance infusion.
Bendamustine (Treanda) Receives Additional Warnings and Precautions
On October 31, 2008, the FDA approved safety labeling revisions for bendamustine (Treanda; Cephalon, Inc) for injection, an alkylating drug indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin's lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.
Safety changes for warnings and precautions included data for myelosuppression from 2 studies in which 98% of patients had grade 3 to 4 myelosuppression, and 2% of patients died of myelosuppression-related adverse reactions (neutropenic sepsis, diffuse alveolar hemorrhage with grade 3 thrombocytopenia, pneumonia from opportunistic infection).
Data regarding skin reactions were added to warnings and precautions, for which 1 case of toxic epidermal necrolysis occurred in a study of bendamustine (90 mg/m2) in combination with rituximab. Toxic epidermal necrolysis has been reported for rituximab, but the relationship of toxic epidermal necrolysis to bendamustine has not been determined.
Other malignant neoplasms were added to warnings and precautions, noting reports of premalignant and malignant diseases that developed in patients treated with bendamustine. The link of bendamustine with these diseases has not been determined. Conditions included myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma.
For adverse reactions, data have been updated to include nonhematologic adverse reactions occurring in 5% or more of patients with NHL treated with bendamustine by organ system class (N = 176). Common adverse reactions by organ system class included nausea (75%, gastrointestinal tract), fatigue (57%, general), anorexia (23%, metabolism and nutrition), cough (22%, respiratory tract), headache (21%, nervous system), and rash (16%, skin and subcutaneous tissue). Hematologic laboratory abnormalities were also added: patients with grade 3 to 4 disease had decreased levels of lymphocytes (94%), leukocytes (56%), hemoglobin (11%), neutrophils (60%), and platelets (25%). The most common serious adverse reactions included febrile neutropenia and pneumonia.
Information added to address specific patient populations included similar efficacy between geriatric patients (> age 65 years) and younger patients (< age 65 years) and no difference in efficacy between the sexes. Both of these patient populations were included in CLL and NHL studies
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