Dinutuximab
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS INFUSION REACTIONS AND NEUROTOXICITY WARNING: SERIOUS INFUSION REACTIONS AND NEUROTOXICITY See full prescribing information for complete boxed warning. Infusion Reactions: Life-threatening infusion adverse reactions occur with Unituxin. Administer required prehydration and premedication. Immediately interrupt for severe infusion reactions and permanently discontinue for anaphylaxis [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.1) ] . Neurotoxicity: Unituxin causes severe neuropathic pain. Administer intravenous opioid prior to, during, and for 2 hours following completion of the Unituxin infusion.
Severe peripheral sensory neuropathy ranged from 2% to 9% in patients with neuroblastoma. Severe peripheral motor neuropathy has also been reported. Discontinue for severe unresponsive pain, severe sensory neuropathy, and moderate to severe peripheral motor neuropathy [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.2) ] . Infusion Reactions Serious and potentially life-threatening infusion reactions occurred in 26% of patients treated with Unituxin. Administer required prehydration and premedication including antihistamines prior to each Unituxin infusion.
Monitor patients closely for signs and symptoms of an infusion reaction during and for at least four hours following completion of each Unituxin infusion. Immediately interrupt Unituxin for severe infusion reactions and permanently discontinue Unituxin for anaphylaxis ( 2.2, 2.3, 5.1 ). Neurotoxicity Unituxin causes serious neurologic adverse reactions including severe neuropathic pain and peripheral neuropathy. Severe neuropathic pain occurs in the majority of patients. Administer intravenous opioid prior to, during, and for 2 hours following completion of the Unituxin infusion.
In clinical studies of patients with high-risk neuroblastoma, Grade 3 peripheral sensory neuropathy occurred in 2% to 9% of patients. In clinical studies of Unituxin and related GD2-binding antibodies, severe motor neuropathy has occurred. Resolution of motor neuropathy did not occur in all cases. Discontinue Unituxin for severe unresponsive pain, severe sensory neuropathy, and moderate to severe peripheral motor neuropathy ( 2.2, 2.3, 5.2 ).
Glycolipid Disialoganglioside-directed Antibody
Dosing in kidney impairment
Renal Impairment Unituxin has not been studied in patients with renal impairment.
Dosing in liver impairment
Hepatic Impairment Unituxin has not been studied in patients with hepatic impairment.
Preparation and administration
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Recommended Dose The recommended dose of Unituxin is 17.5 mg/m 2 /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 and Clinical Studies ] . Initiate at an infusion rate of 0.875 mg/m 2 /hour for 30 minutes.
The infusion rate can be gradually increased as tolerated to a maximum rate of 1.75 mg/m 2 /hour. Follow dose modification instructions for adverse reactions [see Dosage and Administration ] . [See table below.] X X X [See table below.] X X X
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 , Adverse Reactions , and Clinical Studies ] . [See table below.] [See table below.]
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 ] . Do not administer Unituxin as an intravenous push or bolus.
| Infusion-related reactions [see Warnings and Precautions (5.1)] | |
| Mild to moderate adverse reactions, such as transient rash, fever, rigors, and localized urticaria, that respond promptly to symptomatic treatment | |
| Onset of reaction: | Reduce Unituxin infusion rate to 50% of the previous rate and monitor closely. |
| After resolution: | Gradually increase infusion rate up to a maximum rate of 1.75 mg/m2/hour. |
| Prolonged or severe adverse reactions, such as mild bronchospasm without other symptoms, or angioedema that does not affect the airway | |
| Onset of reaction: | Immediately interrupt Unituxin. |
| After resolution: | If signs and symptoms resolve rapidly, resume Unituxin at 50% of the previous rate and observe closely. |
| First recurrence: | Discontinue Unituxin until the following day.If symptoms resolve and continued treatment is warranted, premedicate with hydrocortisone 1 mg/kg (maximum dose 50 mg) intravenously and administer Unituxin at a rate of 0.875 mg/m2/hour in an intensive care unit. |
| Second recurrence: | Permanently discontinue Unituxin. |
| Neurological disorders of the eye [see Warnings and Precautions (5.2)] | |
| Onset of reaction: | Discontinue Unituxin infusion until resolution. |
| After resolution: | Reduce the Unituxin dose by 50%. |
| First recurrence or if accompanied by visual impairment: | Permanently discontinue Unituxin. |
| Capillary leak syndrome [see Warnings and Precautions (5.3)] | |
| Moderate to severe but not life-threatening capillary leak syndrome | |
| Onset of reaction: | Immediately interrupt Unituxin. |
| After resolution: | Resume Unituxin infusion at 50% of the previous rate. |
| Life-threatening capillary leak syndrome | |
| Onset of reaction: | Discontinue Unituxin for the current cycle. |
| After resolution: | In subsequent cycles, administer Unituxin at 50% of the previous rate. |
| First recurrence: | Permanently discontinue Unituxin. |
| HypotensionSymptomatic hypotension, systolic blood pressure (SBP) less than lower limit of normal for age, or SBP decreased by more than 15% compared to baseline. requiring medical intervention [see Warnings and Precautions (5.4)] | |
| Onset of reaction: | Interrupt Unituxin infusion. |
| After resolution: | Resume Unituxin infusion at 50% of the previous rate.If blood pressure remains stable for at least 2 hours, increase the infusion rate as tolerated up to a maximum rate of 1.75 mg/m2/hour. |
| Severe systemic infection or sepsis [see Warnings and Precautions (5.5)] | |
| Onset of reaction: | Discontinue Unituxin until resolution of infection, and then proceed with subsequent cycles of therapy. |
Drug interactions
Check dinutuximab against a medication listLabel text (1 paragraph)
No drug-drug interaction studies have been conducted with dinutuximab.
Contraindications
Unituxin is contraindicated in patients with a history of anaphylaxis to dinutuximab. History of anaphylaxis to dinutuximab. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproven but suspected cause of clinically apparent acute liver injury.
Dinutuximab is a recombinant chimeric monoclonal antibody to GD2 which is used as an anticancer agent in combination with other antineoplastic agents in the treatment of neuroblastoma. Transient asymptomatic elevations in serum aminotransferase levels are common during dinutuximab therapy, but it has not been linked to instances of clinically apparent liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action, Unituxin may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. 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. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S.
general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.
Breastfeeding (LactMed)
No information is available on the clinical use of dinutuximab during breastfeeding. Because dinutuximab is a large protein molecule with a molecular weight of about 150,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Until more data become available, dinutuximab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. The manufacturer recommends that breastfeeding be discontinued during dinutuximab therapy.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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