UNITUXIN Solution for injection Ref.[10022] Active ingredients: Dinutuximab

• Verify that patients have adequate hematologic, respiratory, hepatic, and renal function prior to initiating each course of Unituxin [see Clinical Studies (14)].
• Administer required premedication and hydration prior to initiation of each Unituxin infusion [see Dosage and Administration (2.2)].

2.1 Recommended Dose

• The recommended dose of Unituxin is 17.5 mg/m²/day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles (Table 1 and Table 2) [see Dosage and Administration (2.4) and Clinical Studies (14)].
• Initiate at an infusion rate of 0.875 mg/m²/hour for 30 minutes. The infusion rate can be gradually increased as tolerated to a maximum rate of 1.75 mg/m²/hour. Follow dose modification instructions for adverse reactions [see Dosage and Administration (2.3)].

Table 1. Schedule of Unituxin Administration for Cycles 1, 3, and 5:

* Cycles 1, 3, and 5 are 24 days in duration.

Table 2. Schedule of Unituxin Administration for Cycles 2 and 4:

* Cycles 2 and 4 are 32 days in duration.

2.2 Required Pre-treatment Guidelines

Intravenous Hydration:

• Administer 0.9% Sodium Chloride Injection, USP 10 mL/kg as an intravenous infusion over 1 hour just prior to initiating each Unituxin infusion.

Analgesics:

• Administer morphine sulfate (50 mcg/kg) intravenously immediately prior to initiation of Unituxin and then continue as a morphine sulfate drip at an infusion rate of 20 to 50 mcg/kg/hour during and for 2 hours following completion of Unituxin.
• Administer additional 25 mcg/kg to 50 mcg/kg intravenous doses of morphine sulfate as needed for pain up to once every 2 hours followed by an increase in the morphine sulfate infusion rate in clinically stable patients.
• Consider using fentanyl or hydromorphone if morphine sulfate is not tolerated.
• If pain is inadequately managed with opioids, consider use of gabapentin or lidocaine in conjunction with intravenous morphine.

Antihistamines and Antipyretics:

• Administer an antihistamine such as diphenhydramine (0.5 to 1 mg/kg; maximum dose 50 mg) intravenously over 10 to 15 minutes starting 20 minutes prior to initiation of Unituxin and as tolerated every 4 to 6 hours during the Unituxin infusion.
• Administer acetaminophen (10 to 15 mg/kg; maximum dose 650 mg) 20 minutes prior to each Unituxin infusion and every 4 to 6 hours as needed for fever or pain. Administer ibuprofen (5 to 10 mg/kg) every 6 hours as needed for control of persistent fever or pain.

2.3 Dosage Modifications

Manage adverse reactions by infusion interruption, infusion rate reduction, dose reduction, or permanent discontinuation of Unituxin (Table 3 and Table 4) [see Warnings and Precautions (5), Adverse Reactions (6), and Clinical Studies (14)].

Table 3. Adverse Reactions Requiring Permanent Discontinuation of Unituxin:

Table 4. Dose Modification for Selected Unituxin Adverse Reactions:

* Symptomatic hypotension, systolic blood pressure (SBP) less than lower limit of normal for age, or SBP decreased by more than 15% compared to baseline.

2.4 Instructions for Preparation and Administration

Preparation:

• Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light by storing in the outer carton. DO NOT FREEZE OR SHAKE vials.
• Inspect visually for particulate matter and discoloration prior to administration. Do not administer Unituxin and discard the single-dose vial if the solution is cloudy, has pronounced discoloration, or contains particulate matter.
• Aseptically withdraw the required volume of Unituxin from the single-dose vial and inject into a 100-mL bag of 0.9% Sodium Chloride Injection, USP. Mix by gentle inversion. Do not shake. Discard unused contents of the vial.
• Store the diluted Unituxin solution under refrigeration (2°C to 8°C). Initiate infusion within 4 hours of preparation.
• Discard diluted Unituxin solution 24 hours after preparation.

Administration:

• Administer Unituxin as a diluted intravenous infusion only [see Dosage and Administration (2.1)]. Do not administer Unituxin as an intravenous push or bolus.

Store Unituxin vials under refrigeration at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light until time of use. Do not freeze or shake the vial.