Naxitamab
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Boxed warning
WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY See full prescribing information for complete boxed warning Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity ( 2.2 , 2.3 , 4 , 5.1 ). Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS).
Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity ( 2.2 , 2.3 , 5.2 ). Serious Infusion-Related Reactions DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Infusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in 4 - 18% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.1) ]. Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least 2 hours following completion of each infusion.
Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.2 , 2.3) , Contraindications (4) , and Warnings and Precautions (5.1) ]. Neurotoxicity DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). Pain of any Grade occurred in 94-100% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.2) ]. Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.2) ].
Glycolipid Disialoganglioside-directed Antibody
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
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Premedications and Supportive Medications Pain Management Prior to and During Infusion [see Warnings and Precautions ]: Five days prior to the first infusion of DANYELZA in each cycle, initiate a 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin. Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion.
Consider use of ketamine for pain that is not adequately controlled by opioids. Premedication: Reduce Risk of Infusion-Related Reactions and Nausea/Vomiting [see Warnings and Precautions and Adverse Reactions ] . Administer intravenous corticosteroids (e.g. methylprednisolone 2 mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 minutes to 2 hours prior to the first infusion of DANYELZA.
Administer corticosteroid premedication for subsequent infusions if a severe infusion reaction occurred with the previous infusion or during the previous cycle. Administer an antihistamine, an H2 antagonist, acetaminophen and an antiemetic 30 minutes prior to each infusion.
Preparation Use appropriate aseptic technique. Visually inspect vial for particulate matter and discoloration prior to administration. Discard vial if solution is discolored, cloudy, or contains particulate matter. Add appropriate quantities of 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP to an empty, sterile intravenous infusion bag large enough to hold the volume needed for the relevant dose as indicated in Table 3.
Allow for 5-10 minutes of passive mixing. Withdraw the required dose of DANYELZA and inject into the infusion bag containing the 5% Albumin (Human), USP and 0.9% Sodium Chloride Injection, USP. Discard any unused portion of DANYELZA left in the vial. Preparation instructions for DANYELZA are described in Table 3. [See table below.] If not used immediately, store the diluted DANYELZA infusion solution at room temperature (15°C to 25°C [59ºF to 77ºF]) for up to 8 hours or refrigerate (2°C to 8°C [36°F to 46°F]) for up to 24 hours.
Once removed from refrigeration, initiate infusion within 8 hours.
Administration Administer DANYELZA as a diluted intravenous infusion as recommended. Do not administer DANYELZA as an intravenous push or bolus [see Dosage and Administration ] . For the first infusion (Cycle 1, Day 1), administer DANYELZA intravenously over 60 minutes. For subsequent infusions, administer DANYELZA intravenously over 30 to 60 minutes, as tolerated. [see Dosage and Administration (2.1 , 2.3) ].
Observe patients for a minimum of 2 hours following each infusion.
| Adverse Reaction | Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 | Dosage Modifications |
|---|---|---|
| Infusion-related reactions [see Warnings and Precautions (5.1)] | Grade 2 Defined as: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours | Reduce DANYELZA infusion rate to 50% of previous rate and monitor closely until recovery to Grade ≤ 1.Increase infusion rate gradually to rate prior to the event as tolerated. |
| Grade 3 Defined as: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae | Immediately interrupt DANYELZA infusion and monitor closely until recovery to Grade ≤ 2.Resume infusion at 50% of the rate prior to the event and increase infusion rate gradually to infusion rate prior to the event as tolerated.Permanently discontinue DANYELZA in patients not responding to medical intervention. | |
| Grade 4 infusion-related reactions Defined as: Life-threatening consequences: urgent intervention indicated or Grade 3 or 4 anaphylaxis | Permanently discontinue DANYELZA. | |
| Pain [see Warnings and Precautions (5.2)] | Grade 3 unresponsive to maximum supportive measures | Permanently discontinue DANYELZA. |
| Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2)] | All Grades | Permanently discontinue DANYELZA. |
| Transverse myelitis [see Warnings and Precautions (5.2)] | All Grades | Permanently discontinue DANYELZA. |
| Peripheral neuropathy [see Warnings and Precautions (5.2)] | Motor neuropathy: Grade 2 or greater or Sensory neuropathy: Grade 3 or 4 | Permanently discontinue DANYELZA. |
| Neurological disorders of the eye [see Warnings and Precautions (5.2)] | Grade 2 to 4 resulting in decreased visual acuity or limiting activities of daily living | Withhold DANYELZA until resolution.If resolved resume DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase DANYELZA to dose prior to onset of symptoms.Permanently discontinue DANYELZA if not resolved within 2 weeks or upon recurrence. |
| Subtotal or total vision loss | Permanently discontinue DANYELZA. | |
| Prolonged urinary retention [see Warnings and Precautions (5.2)] | Persisting following discontinuation of opioids | Permanently discontinue DANYELZA. |
| Myocarditis [see Warnings and Precautions (5.3)] | Grade 2 or 3 | Withhold, reduce dose, or permanently discontinue DANYELZA treatment based on severity and duration. |
| Grade 4 | Permanently discontinue DANYELZA. | |
| Hypertension [see Warnings and Precautions (5.4)] | Grade 3 | Withhold DANYELZA or pause infusion until recovery to ≤ Grade 2.Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase DANYELZA to rate prior to onset of symptoms.Permanently discontinue DANYELZA in patients not responding to medical intervention. |
| Grade 4 | Permanently discontinue DANYELZA. | |
| Orthostatic hypotension [see Warnings and precautions (5.5)] | All grades | Withhold DANYELZA until recovery to Grade ≤ 1.If resolved within 1 week, restart DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms after completion of next cycle, resume to recommended dose for subsequent cycles.If not resolved within 1 week, permanently discontinue DANYELZA. |
| Other Adverse Reactions [see Adverse Reactions (6.1)] | Grade 3 | Withhold DANYELZA until recovery to Grade ≤ 2.If resolved to Grade ≤ 2 resume DANYELZA at same rate.Permanently discontinue DANYELZA if not resolved to Grade ≤2 within 2 weeks. |
| Grade 4 | Permanently discontinue DANYELZA. |
| DANYELZA dose (mg) | DANYELZA volume (mL) | Volume of 5% Albumin (Human), USP (mL) | Total infusion volume achieved by adding sufficient 0.9% Sodium Chloride Injection, USP (mL) | Final concentration of prepared DANYELZA infusion (mg/mL) |
|---|---|---|---|---|
| ≤ 80 | ≤ 20 | 10 | 50 | ≤ 1.6 |
| 81 to 120 | > 20 to 30 | 15 | 75 | 1.1 to 1.6 |
| 121 to 150 | > 30 to 37.5 | 20 | 100 | 1.2 to 1.5 |
Contraindications
4 CONTRAINDICATIONS DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis [see Warnings and Precautions (5.1) ]. History of severe hypersensitivity reaction to naxitamab-gqgk. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Naxitamab is a monoclonal antibody to GD2 that is used in combination with granulocyte-macrophage colony stimulating factor to treat children with relapsed or refractory high risk neuroblastoma of the bone or bone marrow. Naxitamab therapy is associated with transient serum aminotransferase elevations during therapy but 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, DANYELZA may cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1) ]. There are no available data on the use of DANYELZA in pregnant women and no animal reproduction studies have been conducted with DANYELZA. IgG1 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 potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Breastfeeding (LactMed)
No information is available on the clinical use of naxitamab during breastfeeding. Because naxitamab is a large protein molecule with a molecular weight of about 144,000 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. The manufacturer recommends that breastfeeding be discontinued during naxitamab therapy and for 2 months after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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