Moxetumomab Pasudotox

IV Preparation Calculate dose Calculate dose (mg) and number of vials (1 mg/vial) to be reconstituted Final concentration of solution is 1 mg/kg Do not round down for partial vials Individualize dose based on patient’s actual body weight before first dose of first treatment cycle Change dose between cycles if a weight gain >10% observed; do not change dose in the midst of a particular cycle Reconstitution Reconstitute with 1.1 mL of sterile water for injection only; do not use IV solution stabilizer to reconstitute the vial Direct the sterile water along the walls of the vial and not directly at the lyophilized cake or powder Gently swirl the vial until completely dissolved; invert the vial to ensure all cake or powder is dissolved Do not shake Visually inspect reconstituted solution; it should appear clear to slightly opalescent, colorless to slightly yellow, and free from visible particles; do not use if cloudy, discolored, or contains any particles Use reconstituted solution immediately; do not store reconstituted vials Dilution Add 1 mL of IV solution stabilizer to 50 mL 0.9% NaCl infusion bag before adding the reconstituted solution to the infusion bag; vial of IV solution stabilizer is packaged separately Only 1 vial of IV solution stabilizer should be used per administration; gently invert the bag to mix the solution Withdraw the calculated dose from the reconstituted vial(s) and add to the 0.9% IV bag that contains the solution stabilize Gently invert bag to mix; do not shake Discard any partially used or empty vials of drug and IV solution stabilizer IV Administration Administer diluted solution IV over 30 minutes Do not mix or administer with other medicinal products Flush IV line with 0.9% NaCl after infusion at the same infusion rate to ensure the full dose is delivered Refrigerated diluted solution If the diluted solution is refrigerated, allow it to equilibrate to room temperature for no more than 4 hr before administration

CLS, including life-threatening cases, reported and is characterized by hypoalbuminemia, hypotension, symptoms of fluid overload, and hemoconcentration (see Black Box Warnings, Dosage Modifications, and Dosing Considerations) HUS, including life-threatening cases, reported and is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and progressive renal failure (see Black Box Warnings, Dosage Modifications, and Dosing Considerations) Renal toxicity has been reported; patients who experience HUS, those aged ≥65 yr, or those with baseline renal impairment may be at increased risk for worsening of renal function following treatment Infusion-related reactions may occur; symptoms include chills, cough, dizziness, dyspnea, feeling hot, flushing, headache, hypertension, hypotension, infusion-related reaction, myalgia, nausea, pyrexia, sinus tachycardia, tachycardia, vomiting, or wheezing; premediate with antihistamines and antipyretics; interrupt infusion if severe and treat with corticosteroids before resuming dose Electrolyte abnormalities reported; hypocalcemia is most commonly reported

Pregnancy There are no available data regarding use in pregnant women Based on mechanism of action and findings in nonpregnant female animals, moxetumomab pasudotox is expected to cause maternal and embryo-fetal toxicity when administered to pregnant women Contraception Women of reproductive potential should use effective contraception during treatment and for at least 30 days after the last dose Lactation No data are available regarding the presence of the drug in human milk or the effects on the breastfed child or milk production The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Side effects of Moxetumomab Pasudotox : >10% (All Grades) Creatinine increased (96%) ALT increased (65%) Hypoalbuminemia (64%) AST increased (55%) Hypocalcemia (54%) Hypophosphatemia (53%) Infusion-related reactions (50%) Hemoglobin decreased (43%) Neutrophil count decreased (41%) Hyponatremia (41%) Peripheral edema (39%) Nausea (35%) Capillary leak syndrome (34%) Fatigue (34%) Headache (33%) Pyrexia (31%) Blood bilirubin increased (30%) Hypokalemia (25%) GGT increased (25%) Hypomagnesemia (23%) Constipation (23%) Diarrhea (21%) Anemia (21%) Platelet count decreased (21%) Hyperuricemia (21%) Alkaline phosphatase increased (20%) >10% (Grades 3 or 4) Hemoglobin decreased (15%) Hypophosphatemia (14%) Neutrophil count decreased (11-20%) Platelet count decreased (3.8-11%)

Anti-CD22 recombinant immunotoxin; after the monoclonal antibody binds to CD22, the molecule is internalized; internalization results in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death