Adult Dosing
Pediatric Dosing
Neuroblastoma
- Recommended dose: 17.5 mg/m2/day IV infusion over 10-20 hr for 4 consecutive days for maximum of 5 cycles
- Schedule for cycles 1, 3, and 5 (duration-24 days): Administer dinutuximab on days 4, 5, 6, and 7
- Schedule for cycles 2 and 4 (duration-32 days): Administer dinutuximab on days 8, 9, 10, and 11
- Initial infusion rate: 0.875 mg/m2/hr x 30 min; infusion rate can be gradually increased, as tolerated, to a maximum rate of 1.75 mg/m2/hr
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 dinutuximab infusion
- Analgesics: Administer morphine sulfate IV (50 mcg/kg) just before initiating dinutuximab; continue as a drip at an infusion rate of 20-50 mcg/kg/hour during and for 2 hrs following completion of dinutuximab infusion.Additional 25-50 mcg/kg IV doses can be administered PRN for pain up to once q2hr followed by an increase in the infusion rate in clinically stable patients.Fentanyl or hydromorphone can be used if morphine sulfate is not tolerated; if opioids are inadequate for pain management, use gabapentin or lidocaine in conjunction with IV morphine
- Antihistamines and antipyretics: Diphenhydramine (0.5-1 mg/kg; max. dose 50 mg) IV over 10-15 minutes can be administered starting 20 minutes before initiating dinutuximab and as tolerated q4-6 hrs during the dinutuximab infusion. Acetaminophen (10-15 mg/kg; max. dose 650 mg) can be administered 20 minutes before each dinutuximab infusion and q4-6hrs PRN for fever or pain. Ibuprofen (5-10 mg/kg) q6hrs can be administered PRN for control of persistent fever or pain
Dosage modifications:Adverse reactions can be managed by infusion interruption, infusion rate reduction, dose reduction, or permanent discontinuation of dinutuximab.
Note- Before initiating each course of dinutuximab [IV], adequate hematologic, respiratory, hepatic, and renal function should be verified
- Before initiation of each infusion of dinutuximab [IV], premedication and hydration should be administered
- Dinutuximab [IV] should not be administered as intravenous push or bolus
- Refer package insert for dosage modifications to manage adverse reactions
[Outline]
- Severe infusion reactions my occur; before initiating dinutuximab therapy, administer required IV hydration and premedication with antihistamines, analgesics, and antipyretics; monitor for signs and symptoms of infusion reactions during and for at least 4 hrs following completion of each dinutuximab infusion and keep CPR medication and equipment available
- Reduce the dinutuximab infusion rate for mild to moderate infusion reactions such as transient rash, fever, rigors, and localized urticaria. Immediately interrupt or permanently discontinue dinutuximab for severe or prolonged infusion reactions. Permanently discontinue dinutuximab for anaphylaxis
- Despite pretreatment with opioid analgesics, abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia may occur with dinutuximab therapy; administer IV opioids before, during, and for 2 hrs following completion of the infusion. Reduce the infusion rate to 0.875 mg/m2/hr for severe pain. Discontinue therapy if pain is not adequately controlled in spite of reduction in infusion rate and provide maximum supportive measures
- Permanently discontinue dinutuximab in patients with Grade 2 peripheral motor neuropathy, Grade 3 sensory neuropathy interfering with daily activities for > 2 weeks, or Grade 4 sensory neuropathy
- If symptomatic or severe capillary leak syndrome occurs, immediately interrupt or discontinue therapy and provide supportive management
- Administer IV hydration before initiating dinutuximab therapy and monitor blood pressure during treatment. Immediately interrupt or discontinue dinutuximab and provide supportive management in patients with symptomatic hypotension, systolic blood pressure (SBP) less than lower limit of normal for age, or SBP that is decreased by more than 15% compared to baseline
- Discontinue dinutuximab therapy in patients who develop systemic infection until the infection is resolved
- Interrupt dinutuximab therapy in patients experiencing dilated pupil with sluggish light reflex or other visual disturbances that do not cause visual loss. Upon resolution and if continued treatment with dinutuximab is warranted, decrease the dose by 50%. Permanently discontinue therapy in patients with recurrent signs or symptoms of an eye disorder despite dose reduction and in patients who experience loss of vision
- Bone marrow suppression may occur leading to severe thrombocytopenia, anemia, neutropenia; monitor peripheral blood counts during dinutuximab therapy
- Electrolyte abnormalities such as hyponatremia, hypokalemia, and hypocalcemia may occur; monitor serum electrolytes daily during dinutuximab therapy
- Atypical hemolytic uremic syndrome has been reported with dinutuximab therapy in one patient. Permanently discontinue therapy and provide supportive management for signs of hemolytic uremic syndrome
- Advise pregnant women of the potential risk to a fetus; advise females of reproductive potential to use effective contraception during treatment, and for two months after the last dose of dinutuximab
Cautions: Use cautiously in:
- Hypotension
- Electrolyte abnormalities
Pregnancy Category: Not Rated; however, because monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester, advise pregnant women of the potential risk to a fetus.
Breastfeeding: Information on the presence of dinutuximab in breast milk is not available; however due to potential for serious adverse reactions in a breastfed infants, advise nursing mothers to discontinue breastfeeding during treatment.
