Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 28 June 2018

Indication(s)

1 INDICATIONS AND USAGE BLINCYTO is a bispecific CD19-directed CD3 T-cell engager indicated for the treatment of adults and children with: B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. (1.1) Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). (1.2) 1.1 MRD-positive B-cell Precursor ALL BLINCYTO is indicated for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. 1.2 Relapsed or Refractory B-cell Precursor ALL BLINCYTO is indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.

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Advisory information

contraindications
4 CONTRAINDICATIONS BLINCYTO is contraindicated in patients with known hypersensitivity to blinatumomab or to any component of the product formulation. Known hypersensitivity to blinatumomab or to any component of the product formulation. (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Cytokine Release Syndrome [see Warnings and Precautions ( 5.1 )] Neurological Toxicities [see Warnings and Precautions ( 5.2 )] Infections [see Warnings and Precautions ( 5.3 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.4 )] Neutropenia and Febrile Neutropenia [see Warnings and Precautions ( 5.5 )] Effects on Ability to Drive and Use Machines [see Warnings and Precautions ( 5.6 )] Elevated Liver Enzymes [see Warnings and Precautions ( 5.7 )] Pancreatitis [see Warnings and Precautions ( 5.8 )] Leukoencephalopathy [see Warnings and Precautions ( 5.9 )] The most common adverse reactions (≥ 20%) were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) 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. MRD-positive B-cell Precursor ALL The safety of BLINCYTO in patients with MRD-positive B-cell precursor ALL was evaluated in two single-arm clinical studies in which 137 patients were treated with BLINCYTO. The median age of the study population was 45 years (range: 18 to 77 years). The most common adverse reactions (≥ 20%) were pyrexia, infusion related reactions, headache, infections (pathogen unspecified), tremor, and chills. Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection. Adverse reactions of Grade 3 or higher were reported in 64% of patients. Discontinuation of therapy due to adverse reactions occurred in 17% of patients; neurologic events were the most frequently reported reasons for discontinuation. There were 2 fatal adverse events that occurred within 30 days of the end of BLINCYTO treatment (atypical pneumonia and subdural hemorrhage). Table 9 summarizes the adverse reactions occurring at a ≥ 10% incidence for any grade or ≥ 5% incidence for Grade 3 or higher. Table 9. Adverse Reactions Occurring at ≥ 10% Incidence for Any Grade or ≥ 5% Incidence for Grade 3 or Higher in BLINCYTO-Treated Patients with MRD-Positive B-cell Precursor ALL (N=137) Adverse Reaction Any Grade * n (%) ≥ Grade 3* n (%) Blood and lymphatic system disorders Neutropenia1 21 (15) 21 (15) Leukopenia2 19 (14) 13 (9) Thrombocytopenia3 14 (10) 8 (6) Cardiac disorders Arrhythmia4 17 (12) 3 (2) General disorders and administration site conditions Pyrexia5 125 (91) 9 (7) Chills 39 (28) 0 (0) Infections and infestations Infections - pathogen unspecified 53 (39) 11 (8) Injury, poisoning and procedural complications Infusion related reaction6 105 (77) 7 (5) Investigations Decreased immunoglobulins7 25 (18) 7 (5) Weight increased 14 (10) 1 (<1) Hypertransaminasemia8 13 (9) 9 (7) Musculoskeletal and connective tissue disorders Back pain 16 (12) 1 (<1) Nervous system disorders Headache 54 (39) 5 (4) Tremor9 43 (31) 6 (4) Aphasia 16 (12) 1 (<1) Dizziness 14 (10) 1 (<1) Encephalopathy10 14 (10) 6 (4) Psychiatric disorders Insomnia1 1 24 (18) 1 (<1) Respiratory, thoracic and mediastinal disorders Cough 18 (13) 0 (0) Skin and subcutaneous tissue disorders Rash1 2 22 (16) 1 (<1) Vascular disorders Hypotension 19 (14) 1 (<1) * Grading based on NCI Common Terminology for Adverse Events (CTCAE) version 4.0. 1 Neutropenia includes febrile neutropenia, neutropenia, and neutrophil count decreased. 2 Leukopenia includes leukopenia and white blood cell count decreased. 3 Thrombocytopenia includes platelet count decreased and thrombocytopenia. 4 Arrhythmia includes bradycardia, sinus arrhythmia, sinus bradycardia, sinus tachycardia, tachycardia and ventricular extrasystoles. 5 Pyrexia includes body temperature increased and pyrexia. 6 Infusion-related reaction is a composite term that includes the term infusion-related reaction and the following events occurring with the first 48 hours of infusion and the event lasted ≤ 2 days: cytokine release syndrome, eye swelling, hypertension, hypotension, myalgia, periorbital edema, pruritus generalized, pyrexia, and rash. 7 Decreased immunoglobulins includes blood immunoglobulin A decreased, blood immunoglobulin G decreased, blood immunoglobulin M decreased, hypogammaglobulinemia, hypoglobulinemia, and immunoglobulins decreased. 8 Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, and hepatic enzyme increased. 9 Tremor includes essential tremor, intention tremor, and tremor. 10 Encephalopathy includes cognitive disorder, depressed level of consciousness, disturbance in attention, encephalopathy, lethargy, leukoencephalopathy, memory impairment, somnolence, and toxic encephalopathy. 11 Insomnia includes initial insomnia, insomnia, and terminal insomnia. 12 Rash includes dermatitis contact, eczema, erythema, rash, and rash maculopapular. Additional adverse reactions in patients with MRD-positive ALL that did not meet the threshold criteria for inclusion in Table 9 were: Blood and lymphatic system disorders: anemia General disorders and administration site conditions: edema peripheral, pain, and chest pain (includes chest pain and musculoskeletal chest pain) Hepatobiliary disorders: blood bilirubin increased Immune system disorders: hypersensitivity and cytokine release syndrome Infections and infestations: viral infectious disorders, bacterial infectious disorders, and fungal infectious disorders Injury, poisoning and procedural complications: medication error and overdose (includes overdose and accidental overdose) Investigations: blood alkaline phosphatase increased Musculoskeletal and connective tissue disorders: pain in extremity and bone pain Nervous system disorders: seizure (includes seizure and generalized tonic-clonic seizure), speech disorder, and hypoesthesia Psychiatric disorders: confusional state, disorientation, and depression Respiratory, thoracic and mediastinal disorders: dyspnea and productive cough Vascular disorders: hypertension (includes blood pressure increased and hypertension) flushing (includes flushing and hot flush), and capillary leak syndrome Philadelphia Chromosome -negative Relapsed or Refractory B -cell Precursor ALL The safety data described below reflect exposure to BLINCYTO in a randomized, open-label, active-controlled clinical study (TOWER Study) in which 376 patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL were treated with BLINCYTO (n = 267) or standard of care (SOC) chemotherapy (n = 109). The median age of BLINCYTO-treated patients was 37 years (range: 18 to 80 years), 60% were male, 84% were White, 7% Asian, 2% were Black or African American, 2% were American Indian or Alaska Native, and 5% were Multiple/Other. The most common adverse reactions (≥ 20%) in the BLINCYTO arm were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia. Adverse reactions of Grade 3 or higher were reported in 87% of patients. Discontinuation of therapy due to adverse reactions occurred in 12% of patients treated with BLINCYTO; neurologic events and infections were the most frequently reported reasons for discontinuation of treatment due to an adverse reaction. Fatal adverse events occurred in 16% of patients. The majority of the fatal events were infections. The adverse reactions occurring at a ≥ 10% incidence for any grade or ≥ 5% incidence for Grade 3 or higher in the BLINCYTO-treated patients in first cycle of therapy are summarized in Table 10. Table 10. Adverse Reactions Occurring at ≥ 10% Incidence for Any Grade or ≥ 5% Incidence for Grade 3 or Higher in BLINCYTO-treated Patients in First Cycle of Therapy Adverse Reaction BLINCYTO (N = 267) Standard of Care (SOC) Chemotherapy (N = 109) Any Grade* n (%) ≥ Grade 3* n (%) Any Grade* n (%) ≥ Grade 3* n (%) Blood and lymphatic system disorders Neutropenia1 84 (31) 76 (28) 67 (61) 61 (56) Anemia2 68 (25) 52 (19) 45 (41) 37 (34) Thrombocytopenia3 57 (21) 47 (18) 42 (39) 40 (37) Leukopenia4 21 (8) 18 (7) 9 (8) 9 (8) Cardiac disorders Arrhythmia5 37 (14) 5 (2) 18 (17) 0 (0) General disorders and administration site conditions Pyrexia 147 (55) 15 (6) 43 (39) 4 (4) Edema6 48 (18) 3 (1) 20 (18) 1 (1) Immune system disorders Cytokine release syndrome7 37 (14) 8 (3) 0 (0) 0 (0) Infections and infestations Infections - pathogen unspecified 74 (28) 40 (15) 50 (46) 35 (32) Bacterial infectious disorders 38 (14) 19 (7) 35 (32) 21 (19) Viral infectious disorders 30 (11) 4 (1) 14 (13) 0 (0) Fungal infectious disorders 27 (10) 13 (5) 15 (14) 9 (8) Injury, poisoning and procedural complications Infusion-related reaction8 79 (30) 9 (3) 9 (8) 1 (1) Investigations Hypertransaminasemia9 40 (15) 22 (8) 13 (12) 7 (6) Nervous system disorders Headache 61 (23) 1 (<1) 30 (28) 3 (3) Skin and subcutaneous tissue disorders Rash10 31 (12) 2 (1) 21 (19) 0 (0) * Grading based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. 1 Neutropenia includes agranulocytosis, febrile neutropenia, neutropenia, and neutrophil count decreased 2 Anemia includes anemia and hemoglobin decreased. 3 Thrombocytopenia includes platelet count decreased and thrombocytopenia. 4 Leukopenia includes leukopenia and white blood cell count decreased. 5 Arrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, bradycardia, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, and tachycardia. 6 Edema includes face edema, fluid retention, edema, edema peripheral, peripheral swelling, and swelling face 7 Cytokine release syndrome includes cytokine release syndrome and cytokine storm. 8 Infusion-related reaction is a composite term that includes the term infusion-related reaction and the following events occurring with the first 48 hours of infusion and the event lasted ≤ 2 days: pyrexia, cytokine release syndrome, hypotension, myalgia, acute kidney injury, hypertension, and rash erythematous. 9 Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, and transaminases increased. 10 Rash includes erythema, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash pruritic, skin exfoliation, and toxic skin eruption. Selected laboratory abnormalities worsening from baseline Grade 0-2 to treatment-related maximal Grade 3-4 in first cycle of therapy are shown in Table 11. Table 11. Selected Laboratory Abnormalities Worsening from Baseline Grade 0-2 to Treatment-related Maximal Grade 3-4* in First Cycle of Therapy BLINCYTO Grade 3 or 4 (%) SOC Chemotherapy Grade 3 or 4 (%) Hematology Decreased lymphocyte count 80 83 Decreased white blood cell count 53 97 Decreased hemoglobin 29 43 Decreased neutrophil count 57 68 Decreased platelet count 47 85 Chemistry Increased ALT 11 11 Increased bilirubin 5 4 Increased AST 8 4 * Includes only patients who had both baseline and at least one laboratory measurement during first cycle of therapy available. R elapsed or Refractory B -cell Precursor ALL Other important adverse reactions from pooled relapsed or refractory B-cell precursor ALL studies were: Blood and lymphatic system disorders: lymphadenopathy, hematophagic histiocytosis, and leukocytosis (includes leukocytosis and white blood cell count increased) General disorders and administration site conditions: chills, chest pain (includes chest discomfort, chest pain, musculoskeletal chest pain, and non-cardiac chest pain), pain, body temperature increased, hyperthermia, and systemic inflammatory response syndrome Hepatobiliary disorders: hyperbilirubinemia (includes blood bilirubin increased and hyperbilirubinemia) Immune system disorders: hypersensitivity (includes hypersensitivity, anaphylactic reaction, angioedema, dermatitis allergic, drug eruption, drug hypersensitivity, erythema multiforme, and urticaria) Injury, poisoning and procedural complications: medication error and overdose (includes overdose, medication error, and accidental overdose) Investigations: weight increased, decreased immunoglobulins (includes immunoglobulins decreased, blood immunoglobulin A decreased, blood immunoglobulin G decreased, blood immunoglobulin M decreased, and hypogammaglobulinemia), blood alkaline phosphatase increased, and hypertransaminasemia Metabolism and nutrition disorders: tumor lysis syndrome Musculoskeletal and connective tissue disorders: back pain, bone pain, and pain in extremity Nervous system disorders: tremor (resting tremor, intention tremor, essential tremor, and tremor), altered state of consciousness (includes altered state of consciousness, depressed level of consciousness, disturbance in attention, lethargy, mental status changes, stupor, and somnolence), dizziness, memory impairment, seizure (includes seizure, and atonic seizure), aphasia, cognitive disorder, speech disorder, hypoesthesia, encephalopathy, and cranial nerve disorders (trigeminal neuralgia, trigeminal nerve disorder, sixth nerve paralysis, cranial nerve disorder, facial nerve disorder, and facial paresis). Psychiatric disorders: insomnia, disorientation, confusional state, and depression (includes depressed mood, depression, suicidal ideation, and completed suicide) Respiratory, thoracic and mediastinal disorders: dyspnea (includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure, respiratory distress, bronchospasm, bronchial hyperreactivity, tachypnea, and wheezing), cough, and productive cough Vascular disorders: hypotension (includes blood pressure decreased, hypotension, hypovolemic shock, and circulatory collapse), hypertension (includes blood pressure increased, hypertension, and hypertensive crisis), flushing (includes flushing and hot flush), and capillary leak syndrome 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of BLINCYTO. 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. Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone [see Warnings and Precautions ( 5.8 )]. 6.3 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity of BLINCYTO has been evaluated using either an electrochemiluminescence detection technology (ECL) or an enzyme-linked immunosorbent assay (ELISA) screening immunoassay for the detection of binding anti-blinatumomab antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies. In clinical studies, less than 2% of patients treated with BLINCYTO tested positive for binding anti-blinatumomab antibodies. Of patients who developed anti-blinatumomab antibodies, 7 out of 9 (78%) had in vitro neutralizing activity. Anti-blinatumomab antibody formation may affect pharmacokinetics of BLINCYTO. If formation of anti-blinatumomab antibodies with a clinically significant effect is suspected, contact Amgen at 1-800-77-AMGEN (1-800-772-6436) to discuss antibody testing. The detection of anti-blinatumomab 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 blinatumomab with the incidence of antibodies to other products may be misleading.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION For the treatment of MRD-positive B-cell Precursor ALL • See Full Prescribing Information for recommended dose by patient weight and schedule. (2.1) - Hospitalization is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. (2.1) - Premedicate with prednisone or equivalent dexamethasone. (2.1) For the treatment of Relapsed or Refractory B -cell Precursor ALL - See Full Prescribing Information for recommended dose by patient weight and schedule. (2.2) - Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle. (2.2) - Premedicate with dexamethasone. (2.2) Refer to Full Prescribing Information for important preparation and administration information. (2.4, 2.5, 2.6) Administer as a continuous intravenous infusion at a constant flow rate using an infusion pump. (2.5, 2.6) - See Section 2.5 for infusion over 24 hours or 48 hours. - See Section 2.6 for infusion over 7 days using Bacteriostatic 0.9% Sodium Chloride Injection, USP (containing 0.9% benzyl alcohol). This option is not recommended for patients weighing less than 22 kg. 2.1 Treatment of MRD-positive B-cell Precursor ALL • A treatment course consists of 1 cycle of BLINCYTO for induction followed by up to 3 additional cycles for consolidation. • A single cycle of treatment of BLINCYTO induction or consolidation consists of 28 days of continuous intravenous infusion followed by a 14-day treatment-free interval (total 42 days). • See Table 1 for the recommended dose by patient weight and schedule. Patients greater than or equal to 45 kg receive a fixed-dose. For patients less than 45 kg, the dose is calculated using the patient’s body surface area (BSA). Table 1. Recommended BLINCYTO Dosage and Schedule for the Treatment of MRD-positive B-cell Precursor ALL Patient Weight Patient Weight Cycle Greater Than or Equal to 45 kg (Fixed -dose) Less Than 45 kg (BSA-based dose) Induction Cycle 1 Days 1-28 28 mcg/day 15 mcg/m2/day (not to exceed 28 mcg/day) Days 29-42 14-day treatment-free interval 14-day treatment-free interval Consolidation Cycles 2 -4 Days 1-28 28 mcg/day 15 mcg/m2/day (not to exceed 28 mcg/day) Days 29-42 14-day treatment-free interval 14-day treatment-free interval • Hospitalization is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. For all subsequent cycle starts and re-initiations (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended. • Premedicate with prednisone or equivalent for MRD-positive B-cell Precursor ALL ○ For adult patients, premedicate with prednisone 100 mg intravenously or equivalent (e.g., dexamethasone 16 mg) 1 hour prior to the first dose of BLINCYTO in each cycle. ○ For pediatric patients, premedicate with 5 mg/m2 of dexamethasone, to a maximum dose of 20 mg prior to the first dose of BLINCYTO in the first cycle and when restarting an infusion after an interruption of 4 or more hours in the first cycle. • For administration of BLINCYTO: ○ See Section 2.5 for infusion over 24 hours or 48 hours. ○ See Section 2.6 for infusion over 7 days using Bacteriostatic 0.9% Sodium Chloride Injection, USP (containing 0.9% benzyl alcohol). This option is available for patients weighing greater than or equal to 22 kg. It is not recommended for use in patients weighing less than 22 kg. 2.2 Treatment of Relapsed or Refractory B-cell Precursor ALL • A treatment course consists of up to 2 cycles of BLINCYTO for induction followed by 3 additional cycles for consolidation and up to 4 additional cycles of continued therapy. • A single cycle of treatment of BLINCYTO induction or consolidation consists of 28 days of continuous intravenous infusion followed by a 14-day treatment-free interval (total 42 days). • A single cycle of treatment of BLINCYTO continued therapy consists of 28 days of continuous intravenous infusion followed by a 56-day treatment-free interval (total 84 days). See Table 2 for the recommended dose by patient weight and schedule. Patients greater than or equal to 45 kg receive a fixed-dose and for patients less than 45 kg, the dose is calculated using the patient’s body surface area (BSA). Table 2. Recommended BLINCYTO Dosage and Schedule for the Treatment of Relapsed or Refractory B-cell Precursor ALL Cycle Patient Weight Patient Weight Greater Than or Equal to 45 kg (Fixed -dose) Less Than 45 kg (BSA-based dose) Induction Cycle 1 Days 1-7 9 mcg/day 5 mcg/m2/day (not to exceed 9 mcg/day) Days 8-28 28 mcg/day 15 mcg/m2/day (not to exceed 28 mcg/day) Days 29-42 14-day treatment-free interval 14-day treatment-free interval Induction Cycle 2 Days 1-28 28 mcg/day 15 mcg/m2/day (not to exceed 28 mcg/day) Days 29-42 14-day treatment-free interval 14-day treatment-free interval Consolidation Cycles 3 -5 Days 1-28 28 mcg/day 15 mcg/m2/day (not to exceed 28 mcg/day) Days 29-42 14-day treatment-free interval 14-day treatment-free interval Continued Therapy Cycles 6 -9 Days 1-28 28 mcg/day 15 mcg/m2/day (not to exceed 28 mcg/day) Days 29-84 56-day treatment-free interval 56-day treatment-free interval • Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle. For all subsequent cycle starts and re-initiation (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended. • Premedicate with dexamethasone. ○ For adult patients, premedicate with 20 mg dexamethasone 1 hour prior to the first dose of BLINCYTO of each cycle, prior to a step dose (such as Cycle 1 Day 8), and when restarting an infusion after an interruption of 4 or more hours. ○ For pediatric patients, premedicate with 5 mg/m2 of dexamethasone, to a maximum dose of 20 mg prior to the first dose of BLINCYTO in the first cycle, prior to a step dose (such as Cycle 1 Day 8), and when restarting an infusion after an interruption of 4 or more hours in the first cycle. • For administration of BLINCYTO: ○ See Section 2.5 for infusion over 24 hours or 48 hours. ○ See Section 2.6 for infusion over 7 days using Bacteriostatic 0.9% Sodium Chloride Injection, USP (containing 0.9% benzyl alcohol). This option is available for patients weighing greater than or equal to 22 kg. It is not recommended for use in patients weighing less than 22 kg. 2.3 Dosage Adjustments If the interruption after an adverse event is no longer than 7 days, continue the same cycle to a total of 28 days of infusion inclusive of days before and after the interruption in that cycle. If an interruption due to an adverse event is longer than 7 days, start a new cycle. Table 3. Dose Modifications for Toxicity Toxicity Grade* Patients Greater Than or Equal to 45 kg Patients Less Than 45 kg Cytokine Release Syndrome (CRS) Grade 3 Withhold BLINCYTO until resolved, then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the toxicity does not recur. Withhold BLINCYTO until resolved, then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the toxicity does not recur. Grade 4 Discontinue BLINCYTO permanently. Neurological Toxicity Seizure Discontinue BLINCYTO permanently if more than one seizure occurs. Grade 3 Withhold BLINCYTO until no more than Grade 1 (mild) and for at least 3 days, then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the toxicity does not recur. If the toxicity occurred at 9 mcg/day, or if the toxicity takes more than 7 days to resolve, discontinue BLINCYTO permanently. Withhold BLINCYTO until no more than Grade 1 (mild) and for at least 3 days, then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the toxicity does not recur. If the toxicity occurred at 5 mcg/m2/day, or if the toxicity takes more than 7 days to resolve, discontinue BLINCYTO permanently. Grade 4 Discontinue BLINCYTO permanently. Other Clinically Relevant Adverse Reactions Grade 3 Withhold BLINCYTO until no more than Grade 1 (mild), then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the toxicity does not recur. If the toxicity takes more than 14 days to resolve, discontinue BLINCYTO permanently. Withhold BLINCYTO until no more than Grade 1 (mild), then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the toxicity does not recur. If the toxicity takes more than 14 days to resolve, discontinue BLINCYTO permanently. Grade 4 Consider discontinuing BLINCYTO permanently. * Based on the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is severe, and Grade 4 is life-threatening. 2.4 Preparation It is very important that the instructions for preparation (including admixing) and administration provided in this section are strictly followed to minimize medication errors (including underdose and overdose) [see Warnings and Precautions ( 5.10 )]. BLINCYTO can be infused over 24 hours (preservative-free) or 48 hours (preservative-free), or 7 days (with preservative). The choice between these options for the infusion duration should be made by the treating physician considering the frequency of the infusion bag changes and the weight of the patient. The 7-day infusion is not recommended for patients weighing less than 22 kg. For preparation, reconstitution, and administration of BLINCYTO: See Section 2.5 for infusion over 24 hours or 48 hours. See Section 2.6 for infusion over 7 days using Bacteriostatic 0.9% Sodium Chloride Injection, USP (containing 0.9% benzyl alcohol). This option is available for patients weighing greater than or equal to 22 kg. It is not recommended for patients weighing less than 22 kg. Call 1-800-77-AMGEN (1-800-772-6436) if you have questions about the reconstitution and preparation of BLINCYTO. 2.4.1 Aseptic Preparation Strictly observe aseptic technique when preparing the solution for infusion since BLINCYTO vials do not contain antimicrobial preservatives. To prevent accidental contamination, prepare BLINCYTO according to aseptic standards, including but not limited to: • Prepare BLINCYTO in a USP <797> compliant facility. • Prepare BLINCYTO in an ISO Class 5 laminar flow hood or better. • Ensure that the admixing area has appropriate environmental specifications, confirmed by periodic monitoring. • Ensure that personnel are appropriately trained in aseptic manipulations and admixing of oncology drugs. • Ensure that personnel wear appropriate protective clothing and gloves. • Ensure that gloves and surfaces are disinfected. 2.4.2 Package Content 1 package BLINCYTO includes 1 vial of BLINCYTO and 1 vial of IV Solution Stabilizer. • Do not use IV Solution Stabilizer for reconstitution of BLINCYTO. IV Solution Stabilizer is provided with the BLINCYTO package and is used to coat the IV bag prior to addition of reconstituted BLINCYTO to prevent adhesion of BLINCYTO to IV bags and IV tubing. • More than 1 package of BLINCYTO may be needed to prepare some of the prescribed doses. 2. 4 .3 Incompatibility Information BLINCYTO is incompatible with di-ethylhexylphthalate (DEHP) due to the possibility of particle formation, leading to a cloudy solution. • Use polyolefin, PVC DEHP-free, or ethyl vinyl acetate (EVA) infusion bags/pump cassettes. • Use polyolefin, PVC DEHP-free, or EVA IV tubing sets. 2.5 24-Hour or 48-Hour Infusion of BLINCYTO 2. 5. 1 Preparation of BLINCYTO Infusion Bag for 24 - or 48- Hour Infusion Verify the prescribed dose and infusion duration for each BLINCYTO infusion bag. To minimize errors, use the speci fic volumes described in Tables 4 to 6 to prepare the BLINCYTO infusion bag. • Table 4 for patients weighing greater than or equal to 45 kg • Tables 5 and 6 for patients weighing less than 45 kg 1. Aseptically add 270 mL 0.9% Sodium Chloride Injection, USP to the IV bag. 2. Aseptically transfer 5.5 mL IV Solution Stabilizer to the IV bag containing 0.9% Sodium Chloride Injection, USP. Gently mix the contents of the bag to avoid foaming. Discard the vial containing the unused IV Solution Stabilizer. 3. Aseptically transfer reconstituted BLINCYTO [ see Dosage and Administration ( 2.5.2 )] into the IV bag containing 0.9% Sodium Chloride Injection, USP and IV Solution Stabilizer. Gently mix the contents of the bag to avoid foaming. • Refer to Tables 4 to 6 for the specific volume of reconstituted BLINCYTO. 4. Under aseptic conditions, attach the IV tubing to the IV bag with the sterile 0.2 micron in-line filter. • Ensure that the IV tubing is compatible with the infusion pump. 5. Remove air from the IV bag. This is particularly important for use with an ambulatory infusion pump. Prime the IV tubing only with the prepared solution for infusion . Do not prime with 0.9% Sodium Chloride Injection, USP. 6. Store at 2°C to 8°C if not used immediately [see Dosage and Administration ( 2.7 )]. Table 4. For Patients Weighing Greater Than or Equal to 45 kg: Volumes to Add to IV Bag 0.9% Sodium Chloride Injection , USP (starting volume) 270 mL IV Solution Stabilizer 5.5 mL Dose Infusion Duration Infusion Rate Reconstituted BLINCYTO 9 mcg/day 24 hours 10 mL/hour 0.83 mL 48 hours 5 mL/hour 1.7 mL 28 mcg/day 24 hours 10 mL/hour 2.6 mL 48 hours 5 mL/hour 5.2 mL* * 2 packages of BLINCYTO are needed for preparation of 28 mcg/day dose infused over 48 hours at a rate of 5 mL/hour. Table 5. For Patients Weighing Less Than 45 kg: Volumes to Add to IV Bag for 5 mcg/m2/day Dose 0.9% Sodium Chloride Injection , USP (starting volume) 270 mL IV Solution Stabilizer 5.5 mL Dose Infusion Duration Infusion Rate BSA (m 2 ) Reconstituted BLINCYTO 5 mcg/m 2 /day 24 hours 10 mL/hour 1.5 – 1.59 0.7 mL 1.4 – 1.49 0.66 mL 1.3 – 1.39 0.61 mL 1.2 – 1.29 0.56 mL 1.1 – 1.19 0.52 mL 1 – 1.09 0.47 mL 0.9 – 0.99 0.43 mL 0.8 – 0.89 0.38 mL 0.7 – 0.79 0.33 mL 0.6 – 0.69 0.29 mL 0.5 – 0.59 0.24 mL 0.4 – 0.49 0.2 mL 5 mcg/m 2 /day 48 hours 5 mL/hour 1.5 – 1.59 1.4 mL 1.4 – 1.49 1.3 mL 1.3 – 1.39 1.2 mL 1.2 – 1.29 1.1 mL 1.1 – 1.19 1 mL 1 – 1.09 0.94 mL 0.9 – 0.99 0.85 mL 0.8 – 0.89 0.76 mL 0.7 – 0.79 0.67 mL 0.6 – 0.69 0.57 mL 0.5 – 0.59 0.48 mL 0.4 – 0.49 0.39 mL Table 6. For Patients Weighing Less Than 45 kg: Volumes to Add to IV Bag for 15 mcg/m2/day Dose 0.9% Sodium Chloride Injection , USP (starting volume) 270 mL IV Solution Stabilizer 5.5 mL Dose Infusion Duration Infusion Rate BSA (m 2 ) Reconstituted BLINCYTO 15 mcg/m 2 /day 24 hours 10 mL/hour 1.5 – 1.59 2.1 mL 1.4 – 1.49 2 mL 1.3 – 1.39 1.8 mL 1.2 – 1.29 1.7 mL 1.1 – 1.19 1.6 mL 1 – 1.09 1.4 mL 0.9 – 0.99 1.3 mL 0.8 – 0.89 1.1 mL 0.7 – 0.79 1 mL 0.6 – 0.69 0.86 mL 0.5 – 0.59 0.72 mL 0.4 – 0.49 0.59 mL 15 mcg/m 2 /day 48 hours 5 mL/hour 1.5 – 1.59 4.2 mL* 1.4 – 1.49 3.9 mL* 1.3 – 1.39 3.7 mL* 1.2 – 1.29 3.4 mL* 1.1 – 1.19 3.1 mL* 1 – 1.09 2.8 mL 0.9 – 0.99 2.6 mL 0.8 – 0.89 2.3 mL 0.7 – 0.79 2 mL 0.6 – 0.69 1.7 mL 0.5 – 0.59 1.4 mL 0.4 – 0.49 1.2 mL * 2 packages of BLINCYTO are needed for preparation of 15 mcg/m2/day dose infused over 48 hours at a rate of 5 mL/hour for patients with a BSA greater than 1.09 m2. 2.5.2 Reconstitution of BLINCYTO 1. Add 3 mL of preservative-free Sterile Water for Injection, USP by directing the water along the walls of the BLINCYTO vial and not directly on the lyophilized powder (resulting in a final BLINCYTO concentration of 12.5 mcg/mL). • Do not reconstitute BLINCYTO with IV Solution Stabilizer. 2. Gently swirl contents to avoid excess foaming. Do not shake. 3. Visually inspect the reconstituted solution for particulate matter and discoloration during reconstitution and prior to infusion. The resulting solution should be clear to slightly opalescent, colorless to slightly yellow. Do not use if solution is cloudy or has precipitated. 2.5.3 Administration • Administer BLINCYTO as a continuous intravenous infusion at a constant flow rate using an infusion pump. The pump should be programmable, lockable, non-elastomeric, and have an alarm. • Prepared BLINCYTO infusion bags [see Dosage and Administration ( 2.5.1 )] should be infused over 24 hours or 48 hours. • The starting volume (270 mL) is more than the volume administered to the patient (240 mL) to account for the priming of the IV tubing and to ensure that the patient will receive the full dose of BLINCYTO. • Infuse BLINCYTO solution according to the instructions on the pharmacy label on the prepared bag at one of the following constant infusion rates: - Infusion rate of 10 mL/hour for a duration of 24 hours, OR - Infusion rate of 5 mL/hour for a duration of 48 hours • The BLINCYTO solution must be administered using IV tubing that contains a sterile, non-pyrogenic, low protein-binding, 0.2 micron in-line filter. • Important Note: Do not flush the BLINCYTO infusion line or intravenous catheter, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof. When administering via a multi -lumen venous catheter, BLINCYTO should be infused through a dedicated lumen. • At the end of the infusion, any unused BLINCYTO solution in the IV bag and IV tubing should be disposed of in accordance with local requirements. 2.6 7-Day Infusion of BLINCYTO using Bacteriostatic Saline This option is not recommended for use in patients weighing less than 22 kg [see Warnings and Precautions ( 5.12 ) and Use in Specific Populations ( 8.4 )] . 2.6 . 1 Preparation of BLINCYTO Infusion Bag for 7 - Day Infusion Verify the prescribed dose and infusion duration for each BLINCYTO infusion bag. To minimize errors, use the specific volumes described in Table 7 to prepare the BLINCYTO infusion bag. 1. Aseptically add 90 mL B acteriostatic 0.9% Sodium Chloride Injection , USP to the empty IV bag. 2. Aseptically transfer 2.2 mL IV Solution Stabilizer to the IV bag containing the saline solution. Gently mix the contents of the bag to avoid foaming. Discard the vial containing the unused IV Solution Stabilizer. 3. Aseptically transfer reconstituted BLINCYTO [ see Dosage and Administration ( 2.6.2 )] into the IV bag containing the saline solution and IV Solution Stabilizer. Gently mix the contents of the bag to avoid foaming. • Refer to Table 7 for the specific volume of reconstituted BLINCYTO. 4. Aseptically add 0.9% Sodium Chloride Injection , USP to the IV bag to a final volume of 110 mL resulting in 0.74% benzyl alcohol. Gently mix the contents of the bag to avoid foaming. • Refer to Table 7 for the specific volume of 0.9% Sodium Chloride Injection, USP. 5. Under aseptic conditions, attach the IV tubing to the IV bag. An in-line filter is not required for a 7-day bag. • Ensure that the IV tubing is compatible with the infusion pump. 6. Remove air from the IV bag. This is particularly important for use with an ambulatory infusion pump. Prime the IV tubing only with the prepared solution for infusion . Do not prime with 0.9% Sodium Chloride Injection , USP. 7. Store at 2°C to 8°C if not used immediately [see Dosage and Administration ( 2.7 )] . Table 7 . For 7 -D ay Infusion: Volumes to A dd to IV Bag for 28 mcg/day and 15 mcg/m 2 /day ; Not Recommended for Patients Less T han 22 kg Bacteriostatic 0.9% Sodium Chloride Injection, USP (starting volume) 90 mL IV Solution Stabilizer 2.2 mL Reconstituted BLINCYTO Specific volume listed below in table Quantity Sufficient (qs) with 0.9% Sodium Chloride Injection , USP to a Final Volume of 110 mL Infusion Duration 7 days Infusion Rate 0.6 mL/hour Patient Weight Dose BSA (m 2 ) Number of BLINCYTO Packages Reconstituted BLINCYTO 0.9% Sodium Chloride Injection , USP to qs to a Final Volume of 110 mL Greater than or equal to 45 kg (fixed-dose) 28 mcg/day 6 16.8 mL 1 mL 22-45 kg (BSA -based dose) 15 mcg/m2/day 1.5 – 1.59 5 14 mL 3.8 mL 1.4 – 1.49 5 13.1 mL 4.7 mL 1.30 – 1.39 5 12.2 mL 5.6 mL 1.20 – 1.29 5 11.3 mL 6.5 mL 1.10 – 1.19 4 10.4 mL 7.4 mL 1 – 1.09 4 9.5 mL 8.3 mL 0.9 – 0.99 4 8.6 mL 9.2 mL 2.6.2 Reconstitution of BLINCYTO 1. Add 3 mL of preservative-free Sterile Water for Injection, USP by directing the water along the walls of the BLINCYTO vial and not directly on the lyophilized powder (resulting in a final BLINCYTO concentration of 12.5 mcg/mL). • Do not reconstitute BLINCYTO with IV Solution Stabilizer. 2. Gently swirl contents to avoid excess foaming. Do not shake. 3. Visually inspect the reconstituted solution for particulate matter and discoloration during reconstitution and prior to infusion. The resulting solution should be clear to slightly opalescent, colorless to slightly yellow. Do not use if solution is cloudy or has precipitated. 2.6 .3 Administration • Administer BLINCYTO as a continuous intravenous infusion at a constant flow rate using an infusion pump. The pump should be programmable, lockable, non-elastomeric, and have an alarm. • Prepared BLINCYTO infusion bags [see Dosage and Administration ( 2.6.1 )] should be infused over 7 days. • The final volume of infusion solution (110 mL) will be more than the volume administered to the patient (100 mL) to account for the priming of the IV tubing and to ensure that the patient will receive the full dose of BLINCYTO. • Infuse BLINCYTO solution according to the instructions on the pharmacy label on the prepared bag at an infusion rate of 0.6 mL/hour for a duration of 7 days. • Important Note: Do not flush the BLINCYTO infusion line or intravenous catheter, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof. When administering via a multi -lumen venous catheter, BLINCYTO should be infused through a dedicated lumen. • At the end of the infusion, any unused BLINCYTO solution in the IV bag and IV tubing should be disposed of in accordance with local requirements. 2.7 Storage Requirements The information in Table 8 indicates the storage time for the reconstituted BLINCYTO vial and prepared infusion bag. Store lyophilized BLINCYTO and IV Solution Stabilizer vials for a maximum of 8 hours at room temperature in the original carton to protect from light [see How Supplied/Storage and Handling ( 16.2 )] . Table 8. Storage Time for Reconstituted BLINCYTO Vial and Prepared BLINCYTO Infusion Bag Maximum Storage Time Room Temperature 23°C to 27°C (73°F to 81°F) Refrigerated 2°C to 8°C (36°F to 46°F) Reconstituted BLINCYTO Vial 4 hours 24 hours Prepared BLINCYTO Infusion Bag ( Preservative - Free ) 48 hours* 8 days Prepared BLINCYTO Infusion Bag ( with Preservative ) 7 days* 14 days * Storage time includes infusion time. If the prepared BLINCYTO infusion bag is not administered within the time frames and temperatures indicated, it must be discarded; it should not be refrigerated again.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Based on its mechanism of action, BLINCYTO may cause fetal harm including B-cell lymphocytopenia when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no data on the use of BLINCYTO in pregnant women. In animal reproduction studies, a murine surrogate molecule administered to pregnant mice crossed the placental barrier ( see Data ). Advise pregnant women of the potential risk to a fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/ N eonatal A dverse R eactions Due to the potential for B-cell lymphocytopenia in infants following exposure to BLINCYTO in-utero, the infant’s B lymphocytes should be monitored before the initiation of live virus vaccination [see Warnings and Precautions ( 5.11 )]. Data Animal Data Animal reproduction studies have not been conducted with blinatumomab. In embryo-fetal developmental toxicity studies, a murine surrogate molecule was administered intravenously to pregnant mice during the period of organogenesis. The surrogate molecule crossed the placental barrier and did not cause embryo-fetal toxicity or teratogenicity. The expected depletions of B and T cells were observed in the pregnant mice, but hematological effects were not assessed in fetuses. 8.2 Lactation Risk Summary There is no information regarding the presence of blinatumomab in human milk, the effects on the breastfed infant, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from BLINCYTO, including B-cell lymphocytopenia, advise patients not to breastfeed during and for at least 48 hours after treatment with BLINCYTO. 8.3 Females and Males of Reproductive Potential Based on its mechanism of action, BLINCYTO may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating BLINCYTO treatment. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for at least 48 hours after the last dose of BLINCYTO. 8.4 Pediatric Use The safety and efficacy of BLINCYTO have been established in pediatric patients with relapsed or refractory B-cell precursor ALL. Use of BLINCYTO is supported by a single-arm trial in pediatric patients with relapsed or refractory B-cell precursor ALL. This study included pediatric patients in the following age groups: 10 infants (1 month up to less than 2 years), 40 children (2 years up to less than 12 years), and 20 adolescents (12 years to less than 18 years). No differences in efficacy were observed between the different age subgroups. The efficacy has also been established based on extrapolation from adequate and well-controlled studies in adults with MRD-positive B-cell precursor ALL. In general, the adverse reactions in BLINCYTO-treated pediatric patients were similar in type to those seen in adult patients with relapsed or refractory B-cell precursor ALL [see Adverse Reactions ( 6.1 )]. Adverse reactions that were observed more frequently (≥ 10% difference) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%). In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%). The steady-state concentrations of blinatumomab were comparable in adult and pediatric patients at the equivalent dose levels based on BSA-based regimens. Benzyl Alcohol Toxicity in Pediatric Patients Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. When prescribing BLINCYTO (with preservative) in pediatric patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative) (contains 7.4 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Warnings and Precautions ( 5.12 )]. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO solution for infusion contain benzyl alcohol and are not recommended for use in patients weighing less than 22 kg. Prepare BLINCYTO solution for infusion with preservative-free saline (24- or 48-hour bags) for use in patients weighing less than 22 kg [see Dosage and Administration ( 2.5 ) ]. 8.5 Geriatric Use Of the total number of patients with ALL treated in clinical studies of BLINCYTO approximately 12% were 65 and over, while 2% were 75 and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. However, elderly patients experienced a higher rate of serious infections and neurological toxicities, including cognitive disorder, encephalopathy, and confusion [see Warnings and Precautions ( 5.2 , 5.3 )].

Interactions

7 DRUG INTERACTIONS No formal drug interaction studies have been conducted with BLINCYTO. Initiation of BLINCYTO treatment causes transient release of cytokines that may suppress CYP450 enzymes. The highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the second cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index. In these patients, monitor for toxicity (eg, warfarin) or drug concentrations (eg, cyclosporine). Adjust the dose of the concomitant drug as needed [see Clinical Pharmacology ( 12.2 , 12.3 )].

More information

Category Value
Authorisation number BLA125557
Orphan designation No
Product NDC 55513-160
Date Last Revised 04-05-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 1597267
Storage and handling 16.2 Storage and Handling Store BLINCYTO and IV Solution Stabilizer vials in the original package refrigerated at 2°C to 8°C (36°F to 46°F) and protect from light until time of use. Do not freeze. Store and transport the prepared IV bag containing BLINCYTO solution for infusion at 2°C to 8°C (36°F to 46°F) conditions. Ship in packaging that has been validated to maintain temperature of the contents at 2°C to 8°C (36°F to 46°F). Do not freeze.
Marketing authorisation holder Amgen Inc
Warnings WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES Cytokine Release Syndrome (CRS), which may be life -threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.1 )]. Neurological toxicities, which may be severe, life -threatening, or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.2 )]. WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES See full prescribing information for complete boxed warning. Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended. ( 2.3 , 5.1 ) Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended. ( 2.3 , 5.2 )