Blinatumomab Dosage

Usual Adult Dose for Acute Lymphoblastic Leukemia

A SINGLE CYCLE OF TREATMENT CONSISTS OF 4 WEEKS OF CONTINUOUS IV INFUSION FOLLOWED BY A 2 WEEK TREATMENT FREE INTERVAL:
For patients at least 45 kg in weight:
-Cycle 1:
9 mcg/day IV via continuous infusion on Days 1 through 7 and 28 mcg/day IV via continuous infusion on Days 8 through 28
-Subsequent cycles:
28 mcg/day IV via continuous infusion on Days 1 through 28

PREMEDICATION:
-The patient should be premedicated with dexamethasone 20 mg IV 1 hour prior to the first dose of each cycle, prior to a step dose (such as Cycle 1 day 8), or when restarting an infusion after an interruption of 4 or more hours.

Comments:
-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 reinitiation (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended.
-The infusion line should not be flushed especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof.
-This drug should be administered as a continuous IV infusion at a constant flow rate using an infusion pump. The pump should be programmable, lockable, non-elastomeric, and have an alarm.
-The infusion line should not be flushed especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof.
-The infusion bags should be infused over 24 or 48 hours.

Uses: For the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Renal Dose Adjustments

CrCl 30 mL/min or more: No adjustment recommended
CrCl less than 30 mL/min: Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

DOSE MODIFICATION GUIDELINES FOR ADVERSE EVENTS:
-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.

Cytokine Release Syndrome (CRS) Toxicity:
-Grade 3: Withhold therapy until resolved, and then restart at 9 mcg/day. Escalate to 28 mcg/ day after 7 days if the toxicity does not recur.
-Grade 4: Discontinue therapy permanently.

Neurological Toxicity:
-Seizure: Discontinue therapy permanently if more than one seizure occurs.
-Grade 3: Withhold therapy until no more than Grade 1 and for at least 3 days, then restart therapy 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 therapy permanently.
-Grade 4: Discontinue therapy permanently.

Other Clinically Relevant Adverse Reactions:
-Grade 3: Withhold therapy until no more than Grade 1, and then restart therapy 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 therapy permanently.
-Grade 4: Consider discontinuing therapy permanently.

Precautions

US BOXED WARNINGS:
-CYTOKINE RELEASE SYNDROME (CRS): Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving this drug. Interrupt or discontinue therapy as recommended.
-NEUROLOGICAL TOXICITIES: Neurological toxicities, which may be severe and life-threatening, or fatal, have occurred in patients receiving this drug. Interrupt or discontinue therapy as recommended.

The safety and efficacy of this drug has not been established in patients less than 18 years of age.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
-This drug should be administered as a continuous IV infusion at a constant flow rate using an infusion pump.
-Do not flush the infusion line especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications.
-This drug should be infused through a dedicated lumen.

General:
-Any unused solution in the IV bag and IV lines should be disposed of in accordance with local requirements.

Reconstitution/preparation/storage advice:
-Refer to the manufacturer product information.

Patient advice:
Contact a healthcare provider for any of the following:
-Symptoms that may be associated with cytokine release syndrome and infusion reactions including pyrexia, fatigue, nausea, vomiting, chills, hypotension, rash, and wheezing.
-Symptoms of neurological toxicities including convulsions, speech disorders, and confusion.
-Symptoms of infections including pneumonia.
If there is a problem with the pump or it alarms, patients should contact their healthcare provider.
Additional patient advice:
-Patients should be advised to refrain from driving and engaging in hazardous activities such as operating machinery while being treated.
-The area around the IV catheter should be kept clean to reduce the risk of infection.
-The patient should not adjust the setting on the infusion pump.