BLINCYTO- blinatumomab kit

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

BLINATUMOMAB (UNII: 4FR53SIF3A) (BLINATUMOMAB - UNII:4FR53SIF3A)

Available from:

Amgen Inc

INN (International Name):

BLINATUMOMAB

Composition:

BLINATUMOMAB 12.5 ug in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

BLINCYTO is indicated for the treatment of CD19-positive 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 adult and pediatric patients. BLINCYTO is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients. BLINCYTO is contraindicated in patients with known hypersensitivity to blinatumomab or to any component of the product formulation. Risk Summary Based on its mechanism of action, BLINCYTO may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data on the use of BLINCYTO in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, a murine surrogate molecule administered to pregnant mice crossed the placental barrier (see Data) . Blinatumomab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on expression of CD19 on B-cells and the finding of B-cell depletion in non-pregnant animals, blinatumomab can cause B-cell lymphocytopenia in infants exposed to blinatumomab in-utero. Advise pregnant women of the potential risk to a fetus. 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/Neonatal Adverse Reactions 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. 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 breastfed infants from BLINCYTO, including B-cell lymphocytopenia, advise patients not to breastfeed during treatment with BLINCYTO and for 48 hours after the last dose. 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 with BLINCYTO and for 48 hours after the last dose. Minimal Residual Disease (MRD)-Positive B-cell Precursor ALL The safety and efficacy of BLINCYTO for the treatment of CD19-positive 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% have been established in pediatric patients. Use of BLINCYTO is supported by evidence from two randomized, controlled trials (Study AALL1331 NCT02101853 and Study 20120215 NCT02393859) in pediatric subjects with first relapsed B-cell precursor ALL. Both studies included pediatric patients with MRD-positive B-cell precursor ALL. The studies included pediatric patients treated with BLINCYTO in the following age groups: 6 infants (1 month up to less than 2 years), 165 children (2 years up to less than 12 years), and 70 adolescents (12 years to less than 17 years). In general, the adverse reactions in BLINCYTO-treated pediatric patients were similar in type to those seen in adult patients with MRD-positive ALL [see Adverse Reactions (6.1)] , and no differences in safety were observed between the different pediatric age subgroups. Relapsed or Refractory B-cell Precursor ALL 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 [see Clinical Studies (14.2)] . In general, the adverse reactions in BLINCYTO-treated pediatric patients with relapsed or refractory ALL 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) with relapsed or refractory ALL, 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%). Benzyl Alcohol Toxicity in Neonates Serious and fatal adverse reactions, including "gasping syndrome," can occur in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) treated with benzyl alcohol-preserved drugs intravenously. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high concentrations of benzyl alcohol and its metabolite in the blood and urine (blood concentration 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. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known [see Warnings and Precautions (5.12)] . Use the preservative-free formulations of BLINCYTO where possible in neonates. When prescribing BLINCYTO (with preservative) in neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative). The BLINCYTO 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL [see Warnings and Precautions (5.12)] . Benzyl alcohol administration may contribute to metabolic acidosis in pediatric patients, particularly those with immaturity of the metabolic pathway for alcohol, or those with underlying conditions or receiving concomitant medications that could predispose to acid base imbalance. Monitor these patients during use of BLINCYTO (with preservative) for new or worsening metabolic acidosis. 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)] .

Product summary:

Each BLINCYTO package (NDC 55513-160-01) contains: 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. BLINCYTO and IV Solution Stabilizer vials may be stored for a maximum of 8 hours at room temperature [23°C to 27°C (73°F to 81°F)] in the original carton to protect from light.

Authorization status:

Biologic Licensing Application

Patient Information leaflet

Amgen Inc
----------
This Medication Guide has been approved by the
U.S. Food and Drug Administration.
Revised: 6/2023
Medication Guide
BLINCYTO® (blin sye toe)
(blinatumomab)
for injection
What is the most important information I should know about BLINCYTO?
Call your healthcare provider or get emergency medical help right away
if you get any of the symptoms
listed below.
BLINCYTO may cause serious side effects that can be severe,
life-threatening, or lead to
death, including:
•
Cytokine Release Syndrome (CRS) and Infusion Reactions. Symptoms of
CRS and infusion
reactions may include:
•
fever
•
tiredness or weakness
•
dizziness
•
headache
•
low blood pressure
•
nausea
•
vomiting
•
chills
•
face swelling
•
wheezing or trouble breathing
•
skin rash
•
Neurologic problems. Symptoms of neurologic problems may include:
•
seizures
•
difficulty in speaking or slurred speech
•
loss of consciousness
•
trouble sleeping
•
confusion and disorientation
•
loss of balance
•
headache
•
difficulty with facial movements, hearing,
vision, or swallowing
•
tremors
Your healthcare provider will check for these problems during
treatment with BLINCYTO. Your
healthcare provider may temporarily stop or completely stop your
treatment with BLINCYTO, if you
have severe side effects.
See “What are the possible side effects of BLINCYTO?” below for
other side effects of BLINCYTO.
What is BLINCYTO?
BLINCYTO is a prescription medicine used to treat adults and children
with:
•
B-cell precursor acute lymphoblastic leukemia (ALL) in remission when
only a small number of
cancer cells remain in the body (minimal residual disease)
•
B-cell precursor ALL that has come back or did not respond to previous
treatments
ALL is a cancer of the blood in which a particular kind of white blood
cell is growing out of control.
Who should not receive BLINCYTO?
Do not receive BLINCYTO if you are allergic to blinatumomab or to any
of the ingredients of
BLINCYTO. See the end of this Medication Guide for a complete lis

Summary of Product characteristics

BLINCYTO- BLINATUMOMAB
AMGEN INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BLINCYTO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR BLINCYTO.
BLINCYTO (BLINATUMOMAB) FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2014
WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGICAL TOXICITIES
INCLUDING
IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
_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 AND
TREAT WITH
CORTICOSTEROIDS AS RECOMMENDED. (2.3, 5.1)
NEUROLOGICAL TOXICITIES, INCLUDING IMMUNE EFFECTOR CELL-ASSOCIATED
NEUROTOXICITY
SYNDROME (ICANS), WHICH MAY BE SEVERE, LIFE-THREATENING, OR FATAL,
OCCURRED IN
PATIENTS RECEIVING BLINCYTO. INTERRUPT OR DISCONTINUE BLINCYTO AS
RECOMMENDED.
(2.3_, _5.2)
RECENT MAJOR CHANGES
Boxed Warning
2/2024
Indications and Usage (1.1)
6/2023
Dosage and Administration (2.4, 2.6)
6/2023
Warnings and Precautions, Neurological Toxicities including Immune
Effector Cell-
Associated Neurotoxicity (5.2)
2/2024
Warnings and Precautions, Effects on Ability to Drive and Use Machines
(5.6)
2/2024
Warnings and Precautions, Benzyl Alcohol Toxicity in Neonates (5.12)
6/2023
Warnings and Precautions, Embryo-Fetal Toxicity (5.13)
6/2023
INDICATIONS AND USAGE
BLINCYTO is a bispecific CD19-directed CD3 T-cell engager indicated
for the treatment of adult and
pediatric patients with:
CD19-positive 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%. (1.1)
Relapsed or refractory CD19-positive B-cell precursor acute
lymphoblastic leukemia (ALL). (1.2)
DOSAGE AND ADMINISTRATION
FOR THE TREATMENT OF MRD-POSITIVE B-CELL PRECURSOR ALL
-
-
-
FOR THE TREATMENT OF RELAPSED OR REFRACTORY B-CELL PRECURSOR ALL
-
-
-
Refer to Full Prescribing Information for im