LUMOXITI Powder for solution for injection Ref.[10359] Active ingredients:

2.1 Recommended Dosage

The recommended dose of LUMOXITI is 0.04 mg/kg administered as a 30-minute intravenous infusion on Days 1, 3, and 5 of each 28-day cycle. Continue LUMOXITI treatment for a maximum of 6 cycles, disease progression, or unacceptable toxicity.

2.2 Recommended Concomitant Treatment

Hydration

Intravenously administer 1 L of isotonic solution (e.g., 5% Dextrose Injection, USP and 0.45% or 0.9% Sodium Chloride Injection, USP) over 2‑4 hours before and after each LUMOXITI infusion. Administer 0.5 L to patients under 50 kg.

Advise all patients to adequately hydrate with up to 3 L (twelve 8‑oz glasses) of oral fluids (e.g., water, milk, or juice) per 24 hours on Days 1 through 8 of each 28‑day cycle. In patients under 50 kg, up to 2 L (eight 8‑oz glasses) per 24 hours is recommended.

Monitor fluid balance and serum electrolytes to avoid fluid overload and/or electrolyte abnormalities [see Warnings and Precautions (5.2,5.5)].

Thromboprophylaxis

Consider low-dose aspirin on Days 1 through 8 of each 28-day cycle.

Monitor for signs and symptoms of thrombosis [see Warnings and Precautions (5.2)].

Premedication

Premedicate 30‑90 minutes prior to each LUMOXITI infusion with:

• An antihistamine (e.g., hydroxyzine or diphenhydramine)
• Acetaminophen antipyretic
• A histamine‑2 receptor antagonist (e.g., ranitidine, famotidine, or cimetidine)

If a severe infusion related reaction occurs, interrupt the LUMOXITI infusion and institute appropriate medical management. Administer an oral or intravenous corticosteroid approximately 30 minutes before resuming, and before each LUMOXITI infusion thereafter [see Warnings and Precautions (5.4)].

Post-infusion Medication

• Consider oral antihistamines and antipyretics for up to 24 hours following LUMOXITI infusions.
• An oral corticosteroid (e.g., 4 mg dexamethasone) is recommended to decrease nausea and vomiting.
• Maintain adequate oral fluid intake.

2.3 Monitoring to Assess Safety

Manage adverse reactions by withholding and/or discontinuing LUMOXITI as described below.

Identify Capillary Leak Syndrome (CLS) and Hemolytic Uremic Syndrome (HUS) based on clinical presentation (see Table 1).

Table 1. Monitoring for CLS and HUS:

Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Capillary Leak Syndrome (CLS)

Patients who experience Grade 2 or higher CLS should receive appropriate supportive measures, including treatment with oral or intravenous corticosteroids, with monitoring of weight, albumin levels, and blood pressure until resolution [see Warnings and Precautions (5.1)].

Table 2. CLS Grading and Management Guidance:

Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Hemolytic Uremic Syndrome (HUS)

Discontinue LUMOXITI in patients with HUS. Treat with appropriate supportive measures and fluid replacement, with monitoring of blood chemistry, complete blood counts, and renal function until resolution [see Warnings and Precautions (5.2)].

Increased Creatinine

For patients with baseline serum creatinine within normal limits, delay dosing for Grade 2 or higher creatinine increases (greater than 1.5‑times baseline or the upper limit of normal). Resume LUMOXITI upon recovery to Grade 1 (1‑ to 1.5‑times baseline, or between the upper limit of normal and 1.5‑times the upper limit of normal).

For patients with baseline serum creatinine of Grades 1 or 2, delay dosing for creatinine increases to Grade 3 or higher (greater than 3‑times baseline or the upper limit of normal). Resume LUMOXITI upon recovery to baseline grade or lower [see Warnings and Precautions (5.3)].

2.4 Instructions for Reconstitution, Dilution, and Administration

LUMOXITI must be reconstituted and diluted by a healthcare provider using aseptic technique. Refer to the Healthcare Provider Instructions for Use for LUMOXITI for full reconstitution, dilution, and administration information.

Step 1: Calculate Dose

• Calculate the dose (mg) and the number of LUMOXITI vials (1 mg/vial) to be reconstituted. The final concentration of the reconstituted LUMOXITI solution is 1 mg/mL.
  • DO NOT round down for partial vials.
• Individualize dosing based on the patient’s actual body weight prior to the first dose of the first treatment cycle.
  • A change in dose should only be made between cycles when a change in weight of greater than 10% is observed from the weight used to calculate the first dose of the first treatment cycle. No change in dose should be made during a particular cycle.

Step 2: Reconstitution

Reconstitute LUMOXITI vials with Sterile Water for Injection, USP only.

• Reconstitute each LUMOXITI (1 mg/vial) with 1.1 mL Sterile Water for Injection, USP. The resulting 1 mg/mL solution allows a withdrawal volume of 1 mL.
  • Direct the Sterile Water for Injection, USP along the walls of the vial and not directly at the lyophilized cake or powder.
  • DO NOT reconstitute LUMOXITI vials with the IV Solution Stabilizer.
• Gently swirl the vial until completely dissolved. Invert the vial to ensure all cake or powder in the vial is dissolved. Do not shake.
• Visually inspect that the reconstituted solution is clear to slightly opalescent, colorless to slightly yellow, and free from visible particles. Do not use if solution is cloudy, discolored, or contains any particles.
• Use reconstituted solution immediately. Do not store reconstituted LUMOXITI vials. See Table 3 for storage times and conditions for the reconstituted solution.

Step 3: Dilution

Add the IV Solution Stabilizer to the infusion bag prior to adding LUMOXITI solution to the infusion bag. Vial of IV Solution Stabilizer is packaged separately.

• Obtain a 50 mL 0.9% Sodium Chloride Injection, USP infusion bag.
• Add 1 mL IV Solution Stabilizer to the infusion bag containing 50 mL 0.9% Sodium Chloride Injection, USP.
  • Only one vial of IV Solution Stabilizer should be used per administration of LUMOXITI.
  • Gently invert the bag to mix the solution. Do not shake.
• Withdraw the required volume (calculated from Step 1) of LUMOXITI solution from the reconstituted vial(s).
  • Inject LUMOXITI into the infusion bag containing 50 mL 0.9% Sodium Chloride Injection, USP and 1 mL IV Solution Stabilizer.
  • Gently invert the bag to mix the solution. Do not shake.
• Discard any partially used or empty vials of LUMOXITI and IV Solution Stabilizer.
• See Table 3 for storage times and conditions for the diluted solution.

Step 4: Administration Instructions

For intravenous infusion only.

• Administer the diluted solution intravenously over 30 minutes.
• Do not mix LUMOXITI, or administer as an infusion with other medicinal products.
• After the infusion, flush the intravenous administration line with of 0.9% Sodium Chloride Injection, USP at the same rate as the infusion. This ensures that the full LUMOXITI dose is delivered.

Table 3: Storage Times and Conditions for Reconstituted and Diluted LUMOXITI Solution

Refrigerate LUMOXITI and IV Solution Stabilizer at 2°C to 8°C (36°F to 46°F), in original carton to protect from light. Do not freeze. Do not shake.