Blinatumomab (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- BLINCYTO
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 [see Dosage and Administration (2.4), Warnings and Precautions (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 [see Dosage and Administration (2.4) , Warnings and Precautions (5.2)].
Contraindications
BLINCYTO is contraindicated in patients with known hypersensitivity to blinatumomab or to any component of the product formulation.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1)] Neurological Toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome [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)]
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 (e.g., warfarin) or drug concentrations (e.g., cyclosporine). Adjust the dose of the concomitant drug as needed [see Clinical Pharmacology (12.2, 12.3)].
Mechanism of Action
Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T-cells. It activates endogenous T-cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B-cells. Blinatumomab mediates the formation of a synapse between the T-cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T-cells, which result in redirected lysis of CD19+ cells.
Overdosage
Overdoses have been observed, including one adult patient who received 133-fold the recommended therapeutic dose of BLINCYTO delivered over a short duration. In the dose evaluation phase of a study in pediatric and adolescent patients with relapsed or refractory B-cell precursor ALL, one patient experienced a fatal cardiac failure event in the setting of life-threatening cytokine release syndrome (CRS) at a 30 mcg/m2/day (higher than the maximum tolerated/recommended) dose [see Warnings and Precautions (5.1) and Adverse Reactions (6)]. Overdoses resulted in adverse reactions, which were consistent with the reactions observed at the recommended dosage and included fever, tremors, and headache. In the event of overdose, interrupt the infusion, monitor the patient for signs of adverse reactions, and provide supportive care [see Warnings and Precautions (5.10)]. Consider re-initiation of BLINCYTO at the recommended dosage when all adverse reactions have resolved and no earlier than 12 hours after interruption of the infusion [see Dosage and Administration (2.1, 2.2 and 2.3)].