VYXEOS

2 DOSAGE AND ADMINISTRATION • Induction: VYXEOS (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome via intravenous infusion over 90 minutes on days 1, 3, and 5 and on days 1 and 3 for subsequent cycles of induction, if needed. ( 2.1 ) • Consolidation: VYXEOS (daunorubicin 29 mg/m 2 and cytarabine 65 mg/m 2 ) liposome via intravenous infusion over 90 minutes on days 1 and 3. ( 2.1 ) • See Full Prescribing Information for instructions on preparation and administration. ( 2.3 , 2.4 ) 2.1 Recommended Dosage A full VYXEOS course consists of 1-2 cycles of Induction and up to 2 cycles of Consolidation at the dose and schedule listed in Table 1. Prior to initiating each cycle of VYXEOS, calculate the prior cumulative anthracycline exposure for the patient [see Warnings and Precautions ( 5.3 )] . Administer prophylactic anti-emetics before treatment with VYXEOS. Table 1: Dose and Schedule for VYXEOS Cycle VYXEOS Dose and Schedule First Induction (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome days 1, 3, and 5 Second Induction a (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome days 1 and 3 Consolidation (daunorubicin 29 mg/m 2 and cytarabine 65 mg/m 2 ) liposome days 1 and 3 a Only for patients failing to achieve a response with the first induction cycle. For the first cycle of induction, the recommended dose of VYXEOS is (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome administered via intravenous infusion over 90 minutes on days 1, 3, and 5. Prior to initiating induction, assess cardiac function and obtain liver and renal function studies. For patients who do not achieve remission with the first induction cycle, a second induction cycle may be administered 2 to 5 weeks after the first if there was no unacceptable toxicity with VYXEOS. The recommended dose for the second induction cycle of VYXEOS is (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome administered via intravenous infusion over 90 minutes on days 1 and 3. Administer the first consolidation cycle 5 to 8 weeks after the start of the last induction. The recommended dose for each cycle of consolidation therapy is VYXEOS (daunorubicin 29 mg/m 2 and cytarabine 65 mg/m 2 ) liposome administered via intravenous infusion over 90 minutes on days 1 and 3. Assess cardiac function, complete blood counts, liver and renal function before each consolidation cycle. Do not start VYXEOS consolidation until the absolute neutrophil count recovers to greater than 0.5 Gi/L and the platelet count recovers to greater than 50 Gi/L in the absence of unacceptable toxicity. Administer the second consolidation cycle 5 to 8 weeks after the start of the first consolidation cycle in patients who do not show disease progression or unacceptable toxicity to VYXEOS. 2.2 Dosage Modification Missed Doses of VYXEOS If a planned dose of VYXEOS is missed, administer the dose as soon as possible and adjust the dosing schedule accordingly, maintaining the treatment interval. Hypersensitivity Reactions For hypersensitivity reactions of any grade/severity, interrupt VYXEOS infusion immediately and manage symptoms. Reduce the rate of infusion or discontinue treatment as outlined below [see Warnings and Precautions ( 5.4 )] . • Mild symptoms: Once symptoms resolve, reinitiate infusion at half the prior rate of infusion. Consider premedication with antihistamines and/or corticosteroids for subsequent doses of VYXEOS. • Moderate symptoms: Do not reinitiate infusion. For subsequent doses of VYXEOS, premedicate with antihistamines and/or corticosteroids prior to initiating infusion at same rate. • Severe/life-threatening symptoms: Permanently discontinue VYXEOS treatment, treat according to the standard of care to manage symptoms, and monitor patient until symptoms resolve. Cardiotoxicity Discontinue VYXEOS in patients who exhibit impaired cardiac function unless the benefit of continuing treatment outweighs the risk [see Warnings and Precautions ( 5.3 )] . 2.3 Preparation and Handling Instructions VYXEOS is a hazardous drug. Follow applicable special handling and disposal procedures. 1 VYXEOS is supplied as a single-dose vial and does not contain any preservatives. Do not save any unused portions for later administration. Reconstitute and further dilute VYXEOS prior to intravenous infusion. Reconstitution: • Calculate the VYXEOS dose based on daunorubicin and individual patient's body surface area (BSA). • Calculate the number of vials of VYXEOS based on the daunorubicin dose. • Remove the appropriate number of vials of VYXEOS from the refrigerator and equilibrate to the room temperature for 30 minutes. • Then, reconstitute each vial with 19 mL of Sterile Water for Injection using a sterile syringe and immediately thereafter start a 5-minute timer. • Carefully swirl the contents of the vial for 5 minutes while gently inverting the vial every 30 seconds. • Do not heat, vortex, or shake vigorously. • After reconstitution, let rest for 15 minutes. • The reconstituted product should be an opaque, purple, homogeneous dispersion, essentially free from visible particulates. After reconstitution (but before final dilution), each mL will contain 2.2 mg of daunorubicin and 5 mg of cytarabine. • Use the reconstituted solution immediately. If needed, store the reconstituted solution in the vial refrigerated at 2ºC to 8ºC (36°F to 46°F) for up to 4 hours. Note that the reconstituted product in the vial and the reconstituted product which has been diluted into an infusion solution are stable for a total of 4 hours (not 4 hours each) when stored at 2°C to 8°C. Dilution: • Calculate the volume of reconstituted VYXEOS required using the following formula: [volume required (mL) = dose of daunorubicin (mg/m 2 ) X patient's BSA (m 2 ) ÷ 2.2 (mg/mL)] • Gently invert each vial 5 times prior to withdrawing the reconstituted product for further dilution. • Aseptically withdraw the calculated volume of the reconstituted product from the vial(s) with a sterile syringe and transfer it to an infusion bag containing 500 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. There may be residual product remaining in the vial. Discard unused portion. • Gently invert the bag to mix the solution. The dilution of the reconstituted product results in a deep purple, translucent, homogeneous dispersion, free from visible particulates. • If the diluted infusion solution is not used immediately, store in a refrigerator at 2ºC to 8ºC (36°F to 46°F) for up to 4 hours. If the reconstituted solution in the vial was stored for 4 hours, the diluted infusion solution must be used immediately and cannot be stored for an additional 4 hours. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Only solutions without visible particles should be used. 2.4 Administration Instructions • For intravenous use only. • Do not mix VYXEOS with or administer as an infusion with other drugs. • Administer VYXEOS by constant intravenous infusion over 90 minutes via an infusion pump through a central venous catheter or a peripherally inserted central catheter. An in-line membrane filter may be used for the intravenous infusion of Vyxeos, provided the minimum pore diameter of the filter is greater than or equal to 15 microns. • Flush the line after administration with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.

See official label

1 INDICATIONS AND USAGE VYXEOS is indicated for the treatment of newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.