Naxitamab-gqgk is a glycolipid disialoganglioside (GD2)-binding monoclonal antibody that is indicated in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for the treatment of relapsed or refractory, high-risk neuroblastoma in pediatric patients 1 year of age and older and adult patients who have bone or bone marrow disease and have demonstrated a partial response, minor response, or stable disease to prior therapy. Naxitamab has black box warnings for infusion-related reactions and neurotoxicity.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Administer naxitamab as diluted intravenous (IV) infusion; do NOT give as an IV bolus or push.
-Premedicate with an antihistamine, an H2 antagonist, acetaminophen, and IV corticosteroids prior to naxitamab infusions as recommended.
Dilution:
-Based on the calculated naxitamab dose (and drug volume), add the appropriate amount of 5% Albumin (human) and quantity sufficient 0.9% NaCl Injection to achieve the recommended total infusion volume (accounting for the volume of naxitamab) into an empty, sterile IV infusion bag as follows:
80 mg or less (20 mL or less): Add 10 mL of 5% Albumin and sufficient 0.9% NaCl Injection to a total volume of 50 mL (final concentration, 1.6 mg/mL or less)
81 to 120 mg (more than 20 mL to 30 mL): Add 15 mL of 5% Albumin and sufficient 0.9% NaCl Injection to a total volume of 75 mL (final concentration, 1.1 to 1.6 mg/mL)
121 to 150 mg (more than 30 mL to 40 mL): Add 20 mL of 5% Albumin and sufficient 0.9% NaCl Injection to a total volume of 100 mL (final concentration, 1.2 to 1.5 mg/mL)
-After allowing for 5 to 10 minutes of passive mixing of the 5% Albumin and 0.9% NaCl Injection, add the calculated dose/volume from the naxitamab (4 mg/mL) vial to the infusion bag.
-Discard any unused portion of the naxitamab vial.
-Storage following dilution: Store the diluted solution at room temperature (15 to 25 degrees C; 59 to 77 degrees F) for up to 8 hours or in the refrigerator (2 to 8 degrees C; 36 to 46 degrees F) for up to 24 hours. Infuse within 8 hours once removed from the refrigerator.
IV Infusion:
-Administer the diluted solution IV over 60 minutes for the first infusion (cycle 1 on day 1); administer subsequent infusions over 30 to 60 minutes as tolerated.
-Monitor patients for signs and symptoms of infusion-related reactions during the infusion and for at least 2 hours following the completion of each infusion; infusion interruption, rate reduction, or permanent discontinuation may be necessary depending on the severity of the reaction.
Fatigue including asthenia occurred in 28% and 44% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in 2 single-arm trials.
Tachycardia/sinus tachycardia occurred in 44% (grade 3 or 4, 1.4%) and 84% (grade 3 or 4, 4%) of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in 2 single-arm trials.
Fever that was not considered an infusion reaction occurred in 11% and 28% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in 2 single-arm trials.
Antibody formation occurred in 8% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, antibody formation was reported in 23% of neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72); however, the assay used to detect antibodies was not fully validated in this trial.
Urticaria that was not considered an infusion reaction occurred in 32% (grade 3 or 4, 4%) of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, erythema multiforme (33%), injection site reaction (28%), hyperhidrosis (17%), contusion (15%), erythema (11%), and device related infection (4.2%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Headache (28%; grade 3 or 4, 8%) and depressed level of consciousness (24%; grade 3 or 4, 16%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, headache (18%) and lethargy (14%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Influenza (12%), rhinovirus infection (12%), and upper respiratory tract infection (12%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, rhinovirus infection (14%) and enterovirus infection (13%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Anxiety occurred in 12% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, anxiety (26%) and irritability (25%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Weight loss occurred in 12% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25).
Edema (28%) and peripheral edema (8%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, localized edema (25%), generalized edema (2.8%), and peripheral edema (8.3%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Cough (60%) and rhinorrhea (24%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25); 4% of patients discontinued therapy due to respiratory depression. Additionally, cough (57%), oropharyngeal pain (15%), abnormal breath sounds (15%), rhinorrhea (15%), apnea (4.2%), and hypopnea (2.8%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Gastrointestinal adverse events have been reported in patients with relapsed or refractory, high-risk neuroblastoma who were treated with naxitamab and sargramostim. Patients should receive an antiemetic 30 minutes prior to each naxitamab infusion. Vomiting (60%; grade 3 or 4, 4%), diarrhea (56%; grade 3 or 4, 8%), nausea (56%), and anorexia (16%) occurred in patients who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, vomiting (63%; grade 3 or 4, 2.8%), nausea (57%; grade 3 or 4, 1.4%), anorexia (53%; grade 3 or 4, 4.2%), diarrhea (50%; grade 3 or 4, 4.2%), and constipation (15%) were reported in patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Urinary retention occurred in 4% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in 2 single-arm trials. Urinary retention started on the day of a naxitamab infusion and lasted up to 24 days. Permanently discontinue naxitamab in patients who have urinary retention that does not resolve after stopping opioid medications.
Severe neurotoxicity including neuropathic pain has been reported in patients who were treated with naxitamab. Transverse myelitis was reported in postmarketing surveillance of naxitamab. Permanently discontinue therapy in patients who develop grade 3 pain unresponsive to maximum supportive measures, grade 2 or greater motor neuropathy, grade 3 or 4 peripheral sensory neuropathy, or transverse myelitis. Give prophylactic pain medication for neuropathic pain (e.g., gabapentin) for 12 days per treatment cycle starting 5 days prior to the first naxitamab dose of each cycle. Premedicate with opioids 45 to 60 minutes prior to each naxitamab infusion; IV opioid doses may be given as needed for breakthrough pain during the infusion. Ketamine may be considered if pain is not adequately controlled with opioids. Grade 3 pain (100%; grade 3 or 4, 72%) and peripheral neuropathy (32%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). In this trial, pain typically started during the naxitamab infusion and lasted a median of less than 1 day (up to 62 days) and neuropathy lasted a median of 5.5 days (range, 0 to 22 days). Additionally, pain (94%; grade 3 or 4, 2.8%) and peripheral neuropathy (25%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72). Neuropathy typically started on the day of the infusion and some cases lasted up to 22 days. The term pain included abdominal pain, extremity pain, bone pain, neck pain, non-cardiac chest pain, flank pain, back pain, and musculoskeletal pain. The term peripheral neuropathy included sensory neuropathy, motor neuropathy, paresthesias, and neuralgia.
Reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 2 patients (2.8%) with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 72). Events occurred at 2 and 7 days following the end of the first cycle of naxitamab therapy. Monitor blood pressure during and following each naxitamab infusion and assess for neurologic symptoms (e.g., severe headaches, vision changes, mental status changes). Permanently discontinue therapy in patients who develop symptomatic RPLS.
Hypertension has been reported in patients who were treated with naxitamab. Hypertension typically occurs during the infusion, but it has been reported at up to 9 days after the infusion. Monitor blood pressure during the naxitamab infusion and at least daily on days 1 to 8 of each treatment cycle. Evaluate patients for hypertensive complications including reversible posterior leukoencephalopathy syndrome. Therapy interruption, infusion rate reduction, or permanent discontinuation may be necessary in patients who develop severe hypertension. Hypertension occurred in 28% (grade 3 or 4, 7%) and 44% (grade 3 or 4, 4%) of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in 2 single-arm trials.
Neurological ocular toxicity has been reported in patients who were treated with naxitamab. For grade 2 to 4 ocular toxicity resulting in decreased visual acuity or limiting activities of daily living, hold naxitamab and resume at a reduced dose when the toxicity resolves. Permanently discontinue naxitamab if the toxicity does not resolve within 2 weeks or if a patient experiences subtotal or total vision loss. Neurological ocular disorders including unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, and photophobia occurred in 24% of patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Ocular toxicity lasted a median of 17 days (range, 0 to 84 days); 2 patients (8%) had ocular toxicity that did not resolve at the time of data cutoff. Additionally, neurological ocular disorders were reported in 19% of neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72). Ocular toxicity lasted a median of 1 day (range, less than 1 to 21 days) in this trial.
Hypokalemia/decreased potassium level (63%; grade 3 or 4, 8%) and hyponatremia/decreased sodium level (29%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, hypocalcemia/decreased calcium level (64%; grade 3 or 4, 8%), hypomagnesemia/decreased magnesium level (54%), hypophosphatemia/decreased phosphate level (47%; grade 3 or 4, 5%), hypokalemia (47%; grade 3 or 4, 32%), and hyponatremia (38%; grade 3 or 4, 6%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Increased ALT level (42%; grade 3 or 4, 8%) and hypoalbuminemia/decreased albumin level (50%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, elevated hepatic enzymes including increased ALT (55%; grade 3 or 4, 9%) and AST (49%; grade 3 or 4, 4%) levels and hypoalbuminemia (68%; grade 3 or 4, 7%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Lymphopenia/decreased lymphocyte count (74%; grade 3 or 4, 30%), thrombocytopenia/decreased platelet count (65%; grade 3 or 4, 17%), neutropenia/decreased neutrophil count (61%; grade 3 or 4, 39%), and anemia/decreased hemoglobin level (48%; grade 3 or 4, 4%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, lymphopenia (79%; grade 3 or 4, 56%), thrombocytopenia (71%; grade 3 or 4, 40%), neutropenia (72%; grade 3 or 4, 46%), and anemia (76%; grade 3 or 4, 42%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Hyperglycemia/increased glucose level (74%) and hypoglycemia/decreased glucose level (29%; grade 3 or 4, 8%) were reported in neuroblastoma patients who received naxitamab and sargramostim in a single-arm trial (n = 72).
Serious infusion-related reactions have been reported with naxitamab therapy; serious infusion reactions occurred in 4% to 18% of patients in clinical studies. Monitor patients for signs and symptoms of an infusion-related reaction during the infusion and for at least 2 hours following the completion of each infusion. Signs and symptoms of infusion-related reactions that may occur on the day of or the day after the naxitamab infusion include cardiac arrest; anaphylaxis; hypotension; bronchospasm; stridor; flushing; wheezing; urticaria; dyspnea; fever; face edema; periorbital edema; mouth, tongue, or lip edema; respiratory tract/pulmonary edema; chills; hypoxia; pruritis; maculopapular rash; erythematous rash; and rash. Urgent interventions such as fluid resuscitation, treatment with bronchodilators and corticosteroids, and intensive care unit admission may be required. Therapy interruption, a rate reduction, or discontinuation may be necessary in patients who develop infusion-related reactions; institute appropriate medical management as needed. Premedicate with an antihistamine, an H2-antagonist, and acetaminophen 30 minutes prior to each infusion; give an IV corticosteroid (e.g. methylprednisolone 2 mg/kg IV [maximum dose, 80 mg] or equivalent) 30 minutes to 2 hours prior to the first infusion. If a patient experiences a severe infusion reaction with the previous infusion or during the previous cycle, administer an IV corticosteroid as a premedication for subsequent infusions. Infusion-related reactions (100%; grade 3 or 4, 68%) and anaphylactoid reactions (grade 3 or 4, 12%) occurred in patients with relapsed or refractory, high-risk neuroblastoma who received naxitamab and sargramostim in a single-arm trial (n = 25). Additionally, infusion-related reactions (94%; grade 3 or 4, 32%) and cardiac arrest (grade 4, 1.4%) were reported in neuroblastoma patients who received naxitamab and sargramostim in another single-arm trial (n = 72).
Myocarditis was reported in adolescent patients who received naxitamab in clinical trials and in expanded use programs; it was also reported in postmarketing surveillance of naxitamab. Myocarditis occurred within days of the naxitamab infusion. Therapy interruption, a dose reduction, or permanent discontinuation may be necessary in patients who develop myocarditis.
Orthostatic hypotension was reported in patients who received naxitamab in clinical trials and expanded use programs and in postmarketing surveillance of naxitamab. Orthostatic hypotension occurred within hours to 6 days after the naxitamab infusion; some cases resulted in hospitalization. Therapy interruption, a dose reduction, or permanent discontinuation may be necessary in patients who develop orthostatic hypotension.
Use is contraindicated in patients with a history of severe hypersensitivity reaction (e.g., anaphylaxis) to naxitamab. Serious infusion-related reactions have been reported with naxitamab therapy, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Patients with pre-existing cardiac disease may be at increased risk of developing hypotension; therefore, use naxitamab with caution in these patients. Treatment requires a specialized care setting that has cardiopulmonary resuscitation medication and equipment. Urgent interventions such as fluid resuscitation, treatment with bronchodilators and corticosteroids, and intensive care unit admission may be required. Premedicate with an antihistamine, an H2-antagonist, and acetaminophen 30 minutes prior to each infusion; give an IV corticosteroid (e.g. methylprednisolone 2 mg/kg IV [maximum dose, 80 mg] or equivalent) 30 minutes to 2 hours prior to the first infusion. If a patient experiences a severe infusion reaction with the previous infusion or during the previous cycle, administer an IV corticosteroid as a premedication for subsequent infusions. Monitor patients for signs and symptoms of an infusion-related reaction during the infusion and for at least 2 hours following the completion of each infusion. Therapy interruption, a rate reduction, or discontinuation may be necessary in patients who develop infusion-related reactions; institute appropriate medical management as needed.
Severe neurotoxicity has been reported with naxitamab therapy, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Assess patients for neurologic symptoms. Pain typically started during the naxitamab infusion and lasted a median of less than one day (up to 62 days) in a clinical study. Give prophylactic pain medication for neuropathic pain (e.g., gabapentin) for 12 days per treatment cycle starting 5 days prior to the first naxitamab dose of each cycle. Premedicate with opioids 45 to 60 minutes prior to each naxitamab infusion; IV opioid doses may be given as needed for breakthrough pain during the infusion. Ketamine may be considered if pain is not adequately controlled with opioids. Permanently discontinue therapy in patients who develop grade 3 pain unresponsive to maximum supportive measures, grade 2 or greater motor neuropathy, grade 3 or 4 sensory peripheral neuropathy, transverse myelitis, or RPLS.
Neurological ocular disease (e.g., accommodation disorder, blurred vision, photophobia, mydriasis, unequal pupils, and visual impairment) has been reported with naxitamab therapy. For grade 2 to 4 toxicity resulting in decreased visual acuity or limiting activities of daily living, hold naxitamab and resume at a reduced dose when the toxicity resolves. Permanently discontinue naxitamab if the toxicity does not resolve within 2 weeks or if a patient experiences subtotal or total vision loss.
Do not administer naxitamab in patients who have uncontrolled hypertension. Hypertension typically occurs during the infusion, but it has been reported at up to 9 days after the infusion. Monitor blood pressure during the naxitamab infusion and at least daily on days 1 to 8 of each treatment cycle. Evaluate patients for hypertensive complications including reversible posterior leukoencephalopathy syndrome. Therapy interruption, infusion rate reduction, or permanent discontinuation may be necessary in patients who develop severe hypertension.
Naxitamab may cause fetal harm when administered during pregnancy, based on its mechanism of action. Although there are no data in humans or from animal studies evaluating the use of naxitamab during pregnancy, IgG1 monoclonal antibodies are transported across the placenta. The transfer of these antibodies increases as pregnancy progresses resulting in the largest amount transferred during the third trimester. Discuss the potential hazard to the fetus if naxitamab is used during pregnancy.
Monitor for signs and symptoms of myocarditis during naxitamab therapy. Therapy interruption, a dose reduction, or permanent discontinuation may be necessary in patients who develop myocarditis.
Counsel patients about the reproductive risk and contraception requirements during naxitamab treatment. Females of reproductive potential should receive pregnancy testing prior to starting naxitamab therapy. These patients should avoid pregnancy and use effective contraception during and for 2 months after the last naxitamab dose. Patients who become pregnant while receiving naxitamab should be apprised of the potential hazard to the fetus.
Severe orthostatic hypotension has occurred with naxitamab use, some cases resulted in hospitalization. In patients with symptoms of orthostatic hypotension, monitor postural blood pressure prior to starting naxitamab and as clinically indicated during therapy. Therapy interruption, a dose reduction, or permanent discontinuation may be necessary in patients who develop orthostatic hypotension.
Although it is not known if naxitamab is secreted in human milk or if it has effects on the breast-fed child or on milk production, human IgG is present in human milk. Because of a potential for serious adverse reactions in the breast-fed child from naxitamab, women should discontinue breast-feeding during naxitamab therapy and for 2 months after the last dose.
For the treatment of neuroblastoma:
NOTE: The FDA has designated naxitamab as an orphan drug for the treatment of neuroblastoma.
-for the treatment of relapsed or refractory, high-risk neuroblastoma in the bone or bone marrow in patients who have had a partial response, minor response, or stable disease to prior therapy, in combination with granulocyte-macrophage colony-stimulating factor (sargramostim):
Intravenous dosage:
Adults, Adolescents, and Children: 3 mg/kg (maximum dose of 150 mg) IV on days 1, 3, and 5 in combination with 10 days of sargramostim. Repeat treatment cycles every 4 weeks until complete response (CR) or partial response (PR). Continue treatment every 4 weeks for 5 additional cycles after CR/PR; subsequent cycles may be repeated every 8 weeks until disease progression. Therapy interruption, infusion rate or dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. Premedicate with an antihistamine, an H2-antagonist, acetaminophen, and an antiemetic 30 minutes prior to each infusion. Additionally, give an IV corticosteroid (e.g. methylprednisolone 2 mg/kg IV [maximum dose, 80 mg] or equivalent) 30 minutes to 2 hours prior to the first infusion; IV corticosteroids may be necessary prior to subsequent infusions in patients who have a severe infusion reaction with the previous infusion or during the previous cycle. Give prophylactic pain medication for neuropathic pain (e.g., gabapentin) for 12 days starting 5 days prior to the first naxitamab dose of each cycle. Administer oral opioids 45 to 60 minutes prior to each naxitamab infusion; IV opioid doses may be given as needed for breakthrough pain during the infusion. Ketamine may be considered if pain is not adequately controlled with opioids. Give sargramostim 250 mcg/m2 subcutaneously daily for 5 doses starting 5 days prior to the day 1 naxitamab infusion then give sargramostim 500 mcg/m2 subcutaneously daily on days 1, 2, 3, 4, and 5. If a naxitamab dose is missed, administer the missed dose the following week by day 10; give sargramostim 500 mcg/m2 subcutaneously daily for 5 days starting on the day of the naxitamab infusion. Administer sargramostim at least 1 hour prior to the naxitamab infusion on days that both drugs are given. The overall response rate (ORR) was 45% (CR rate, 36%) in pediatric patients (median age, 5 years; range, 3 to 10 years) with refractory or relapsed, high-risk neuroblastoma who received treatment with naxitamab and sargramostim in a multicenter, single-arm trial (n = 22). In another single-arm trial, the ORR was 34% (CR, 26%) in a subpopulation of patients (n = 38; median age, 5 years; range, 2 to 23 years) with relapsed or refractory, high-risk neuroblastoma who received treatment with naxitamab and sargramostim. In these trials, response was assessed by revised International Neuroblastoma Response Criteria.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicities
Hypertension
Grade 3 toxicity: Hold therapy or interrupt the naxitamab infusion. Resume the infusion at 50% of the previous rate when the toxicity resolves to grade 2 or less; slowly increase the infusion rate to the previous rate as tolerated. Permanently discontinue naxitamab in patients who do not respond to medical intervention.
Grade 4 toxicity: Permanently discontinue naxitamab.
Infusion-Related Reactions
Grade 2 toxicity: Reduce the infusion rate to 50% of the previous rate; slowly increase the infusion rate to the previous rate as tolerated when the toxicity resolves to grade 1 or less.
Grade 3 toxicity: Interrupt the infusion. Resume the infusion at 50% of the previous rate when the toxicity resolves to grade 2 or less; slowly increase the infusion rate to the previous rate as tolerated. Permanently discontinue naxitamab in patients who do not respond to medical intervention.
Grade 4 toxicity OR grade 3 or 4 anaphylaxis: Permanently discontinue naxitamab.
Myocarditis
Grade 2 or 3 toxicity: Hold therapy, dose reduce, or permanently discontinue naxitamab depending on toxicity severity and duration.
Grade 4 toxicity: Permanently discontinue naxitamab.
Neurologic Disorders of the Eye
Grade 2 to 4 toxicity resulting in decreased visual acuity or limiting activities of daily living: Hold naxitamab; resume therapy at 50% of the prior dose when the toxicity resolves. If the reduced dose is tolerated without a recurrence of symptoms, gradually increase the dose to the previous dose. Permanently discontinue naxitamab if the toxicity does not resolve within 2 weeks.
Subtotal or total vision loss: Permanently discontinue naxitamab.
Orthostatic Hypotension
Any grade toxicity: Hold naxitamab; resume therapy at 50% of the prior dose if the toxicity resolves to grade 1 or less within 1 week. If the reduced dose is tolerated without a recurrence of symptoms after completion of next cycle, resume to recommended dose for subsequent cycles. Permanently discontinue naxitamab if the toxicity does not resolve within 1 week.
Pain
Grade 3 pain not responsive to maximum supportive measures: Permanently discontinue naxitamab.
Peripheral Neuropathy
Grade 2 or greater motor neuropathy: Permanently discontinue naxitamab.
Grade 3 or 4 sensory neuropathy: Permanently discontinue naxitamab.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Any grade RPLS: Permanently discontinue naxitamab.
Transverse Myelitis
Any grade toxicity: Permanently discontinue naxitamab.
Urinary Retention
Prolonged retention that persists following discontinuation of opioids: Permanently discontinue naxitamab.
Other Toxicities
Grade 3 toxicity: Hold therapy or interrupt the infusion. Resume the infusion at the previous rate when the toxicity resolves to grade 2 or less; slowly increase the infusion rate to the previous rate as tolerated. Permanently discontinue naxitamab if the toxicity does not resolve to grade 2 or less within 2 weeks.
Grade 4 toxicity: Permanently discontinue naxitamab.
Maximum Dosage Limits:
-Adults
3 mg/kg (max of 150 mg) IV on days 1, 3, and 5 repeated every 4 weeks.
-Adolescents
3 mg/kg (max of 150 mg) IV on days 1, 3, and 5 repeated every 4 weeks.
-Children
3 mg/kg (max of 150 mg) IV on days 1, 3, and 5 repeated every 4 weeks.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Naxitamab is a recombinant humanized monoclonal IgG1 antibody that works by binding to glycolipid disialoganglioside (GD2) on the cell surface of neuroblastoma cells and cells of neuroectodermal origin, including the central nervous system and peripheral nerves. This binding results in cell lysis through antibody-dependent cell-mediated and complement-dependent cytotoxicity.
Naxitamab is administered as an IV infusion. The mean terminal half-life was 8.2 days following treatment with naxitamab 3 mg/kg IV given over 30 minutes. Naxitamab is metabolized into small peptides by catabolic pathway.
-Route-Specific Pharmacokinetics
Intravenous Route
The mean Cmax value was 57.4 mcg/mL (coefficient of variation (CV), 49%) following a single dose of naxitamab 3 mg/kg IV given over 30 minutes.
-Special Populations
Pediatrics
Age (range, 1 to 34 years) had no clinically significant impact on the clearance of naxitamab in a population pharmacokinetic analysis.
Gender Differences
Sex had no clinically significant impact on the clearance of naxitamab in a population pharmacokinetic analysis.
Ethnic Differences
Race had no clinically significant impact on the clearance of naxitamab in a population pharmacokinetic analysis.
Other
Weight
The AUC value in patients weight over 50 kg who received naxitamab 150 mg/day (450 mg/cycle) is not expected to differ clinically compared with the AUC value in patients weighing 30 to 50 kg who received naxitamab 3 mg/kg per day (9 mg/kg per cycle).