Unituxin (dinutuximab)

Unituxin (dinutuximab) is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior firstline multiagent, multimodality therapy.

The most common adverse drug reactions (≥ 25%) in the Unituxin/RA group were pain, pyrexia, thrombocytopenia, lymphopenia, infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and hypocalcemia.

The most common serious adverse reactions (≥ 5%) in the Unituxin/RA group were infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome.

Serious Infusion Reactions

Inform patients and caregivers of the risk of serious infusion reactions and anaphylaxis and to immediately report any signs or symptoms, such as facial or lip swelling, urticaria, difficulty breathing, lightheadedness or dizziness that occur during or within 24 hours following the infusion.

Pain, Peripheral Neuropathy, Prolonged Urinary Retention, And Transverse Myelitis

Inform patients and caregivers of the risk of severe pain, sensory and motor neuropathy, prolonged urinary retention, and transverse myelitis, and to promptly report severe or worsening pain and signs and symptoms such as numbness, tingling, burning, weakness, or inability to urinate.

Neurological Disorders Of The Eye

Inform patients and caregivers of the risk of neurological disorders of the eye and to promptly report signs or symptoms such as blurred vision, photophobia, ptosis, diplopia, or unequal pupil size.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

Inform patients and caregivers of the risk of RPLS and to immediately report signs or symptoms such as severe headache, hypertension, visual changes, lethargy, or seizures.

Capillary Leak Syndrome

Inform patients and caregivers of the risk of capillary leak syndrome and to immediately report any signs or symptoms.

Hypotension

Inform patients and caregivers of the risk of hypotension during the infusion and to immediately report any signs or symptoms.

Infection

Inform patients and caregivers of the risk of infection following treatment and to immediately report any signs or symptoms.

Bone Marrow Suppression

Inform patients and caregivers of the risk of bone marrow suppression, and to promptly report signs or symptoms of anemia, thrombocytopenia, or infection.

Electrolyte Abnormalities

Inform patients and caregivers of the risk of electrolyte abnormalities including hypokalemia, hyponatremia, and hypocalcemia, and to report any signs or symptoms such as seizures, heart palpitations, and muscle cramping.

Atypical Hemolytic Uremic Syndrome

Inform patients and caregivers of the risk of hemolytic uremic syndrome and to report any signs or symptoms such as fatigue, dizziness, fainting, pallor, edema, decreased urine output, or hematuria.

• Verify that patients have adequate hematologic, respiratory, hepatic, and renal function prior to initiating each course of Unituxin.
• Administer required premedication and hydration prior to initiation of each Unituxin infusion.

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 (Tables 1 and 2 ).
• 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.

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

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

Required Pre-Treatment And Guidelines For Pain Management

Intravenous Hydration

• Administer 0.9% Sodium Chloride Injection, USP 10 mL/kg as an intravenous infusion over one 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 two 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.

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-use vial if the solution is cloudy, has pronounced discoloration, or contains particulate matter.
• Aseptically withdraw the required volume of Unituxin from the single-use 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. Do not administer Unituxin as an intravenous push or bolus.

No drug-drug interaction studies have been conducted with dinutuximab.

Embryo-Fetal Toxicity

Advise women of reproductive potential of the potential risk to the fetus if administered during pregnancy and the need for use of effective contraception during and for at least two months after completing therapy.

Lactation

Because of the potential for serious adverse reactions in a breastfed infant, advise a nursing woman to discontinue breastfeeding during treatment with Unituxin.