8.6     Hepatic Impairment
No formal pharmacokinetic studies using BLINCYTO have been conducted in patients with hepatic impairment.

8.7     Renal Impairment
No formal pharmacokinetic studies using BLINCYTO have been conducted in patients with renal impairment. No dose adjustment is needed for patients with baseline creatinine clearance (CrCL) equal to or greater than 30 mL/min. There is no information available in patients with CrCL less than 30 mL/min or patients on hemodialysis [see Clinical Pharmacology (12.3)].

10. OVERDOSAGE
Overdoses have been observed, including one patient who received 133-fold the recommended therapeutic dose of BLINCYTO delivered over a short duration. Overdoses resulted in adverse reactions which were consistent with the reactions observed at the recommended therapeutic dose and included fever, tremors, and headache.  In the event of overdose, interrupt the infusion, monitor the patient for signs of toxicity, and provide supportive care [see Warnings and Precautions (5.9)]. Consider reinitiation of BLINCYTO at the correct therapeutic dose when all toxicities have resolved and no earlier than 12 hours after interruption of the infusion [see Dosage and Administration (2.1)]. 

11. DESCRIPTION
BLINCYTO (blinatumomab) is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 (expressed on cells of B-lineage origin) and CD3 (expressed on T cells). BLINCYTO is produced in Chinese hamster ovary cells.  It consists of 504 amino acids and has a molecular weight of approximately 54 kilodaltons.

Each BLINCYTO package contains 1 vial BLINCYTO and 1 vial IV Solution Stabilizer.

BLINCYTO is supplied in a single-use vial as a sterile, preservative-free, white to off-white lyophilized powder for intravenous administration.  Each single-use vial of BLINCYTO contains 35 mcg blinatumomab, citric acid monohydrate (3.35 mg), lysine hydrochloride (23.23 mg), polysorbate 80 (0.64 mg), trehalose dihydrate (95.5 mg), and sodium hydroxide to adjust pH to 7.0.  After reconstitution with 3 mL of preservative-free Sterile Water for Injection, USP, the resulting concentration is 12.5 mcg/mL blinatumomab. 

IV Solution Stabilizer is supplied in a single-use vial as a sterile, preservative-free, colorless to slightly yellow, clear solution. Each single-use vial of IV Solution Stabilizer contains citric acid monohydrate (52.5 mg), lysine hydrochloride (2283.8 mg), polysorbate 80 (10 mg), sodium hydroxide to adjust pH to 7.0, and water for injection.

12. CLINICAL PHARMACOLOGY

12.1     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.

12.2     Pharmacodynamics
During the continuous intravenous infusion over 4 weeks, the pharmacodynamic response was chara