Naxitamab-gqgk
Brand name: Danyelza
Drug class: Antineoplastic Agents
Warning
Warning: Serious Infusion-related Reactions And Neurotoxicity
See full prescribing information for complete boxed warning
-
Serious Infusion-related Reactions: Naxitamab-gqgk can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each naxitamab-gqgk infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue naxitamab-gqgk based on severity.
-
Neurotoxicity: Naxitamab-gqgk 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 naxitamab-gqgk based on the adverse reaction and severity.
Introduction
Naxitamab-gqgk is a glycolipid disialoganglioside (GD2)-binding monoclonal antibody antineoplastic agent.
Uses for Naxitamab-gqgk
Naxitamab-gqgk has the following uses:
Naxitamab-gqgk is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Naxitamab-gqgk Dosage and Administration
General
Naxitamab-gqgk is available in the following dosage form(s) and strength(s):
Concentrate for injection: 40 mg/10 mL (4 mg/mL) in a single-dose vial.
Dosage
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Pediatric Patients
Dosage and Administration
The recommended dosage of naxitamab-gqgk is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks.
Administer pre-infusion medications and supportive treatment, as appropriate, during infusion.
Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended. Refer to the GM-CSF prescribing information for recommended dosing information.
Consult manufacturer’s labeling for recommended dosage modifications for adverse reactions. Discontinue naxitamab-gqgk and GM-CSF for disease progression or unacceptable toxicity.
Adults
Dosage and Administration
The recommended dosage of naxitamab-gqgk is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks.
Administer pre-infusion medications and supportive treatment, as appropriate, during infusion.
Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended. Refer to the GM-CSF prescribing information for recommended dosing information.
Consult manufacturer’s labeling for recommended dosage modifications for adverse reactions. Discontinue naxitamab-gqgk and GM-CSF for disease progression or unacceptable toxicity.
Cautions for Naxitamab-gqgk
Contraindications
History of severe hypersensitivity reaction to naxitamab-gqgk.
Warnings/Precautions
Serious Infusion-related Reactions
Naxitamab-gqgk can cause serious infusion reactions requiring urgent intervention including fluid resuscitation, administration of bronchodilators and corticosteroids, intensive care unit admission, infusion rate reduction or interruption of naxitamab-gqgk infusion. Infusion-related reactions included hypotension, bronchospasm, hypoxia, and stridor.
Serious infusion-related reactions occurred in 4% of patients in Study 201 and in 18% of patients in Study 12-230. Infusion-related reactions of any grade occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Hypotension of any grade occurred in 100% of patients in Study 201 and 89% of patients in Study 12-230.
In Study 201, 68% of patients experienced grade 3 or 4 infusion reactions; and in Study 12-230, 32% of patients experienced grade 3 or 4 infusion reactions. Anaphylaxis occurred in 12% of patients and 2 patients (8%) permanently discontinued naxitamab-gqgk due to anaphylaxis in Study 201. One patient in Study 12-230 (1.4%) experienced a grade 4 cardiac arrest 1.5 hours following completion of naxitamab-gqgk infusion.
In Study 201, infusion reactions generally occurred within 24 hours of completing a naxitamab-gqgk infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion of naxitamab-gqgk in each cycle. Eighty percent of patients required reduction in infusion rate and 80% of patients had an infusion interrupted for at least one infusion-related reaction.
Premedicate with an antihistamine, acetaminophen, an H2 antagonist and corticosteroid as recommended. Monitor patients closely for signs and symptoms of infusion reactions during and for at least 2 hours following completion of each naxitamab-gqgk infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.
Reduce the rate, interrupt infusion, or permanently discontinue naxitamab-gqgk based on severity and institute appropriate medical management as needed.
Neurotoxicity
Naxitamab-gqgk can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS).
Pain
Pain, including abdominal pain, bone pain, neck pain, and extremity pain, occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Grade 3 pain occurred in 72% of patients in Study 201. One patient in Study 201 (4%) required interruption of an infusion due to pain. Pain typically began during the infusion of naxitamab-gqgk and lasted a median of less than one day in Study 201 (range less than one day and up to 62 days).
Premedicate with drugs that treat neuropathic pain (e.g., gabapentin) and oral opioids. Administer intravenous opioids as needed for breakthrough pain. Permanently discontinue naxitamab-gqgk based on severity.
Transverse Myelitis
Transverse myelitis has occurred with naxitamab-gqgk. Permanently discontinue naxitamab-gqgk in patients who develop transverse myelitis.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Reversible posterior leukoencephalopathy syndrome (RPLS) (also known as posterior reversible encephalopathy syndrome or PRES) occurred in 2 (2.8%) patients in Study 12-230. Events occurred 2 and 7 days following completion of the first cycle of naxitamab-gqgk. Monitor blood pressure during and following naxitamab-gqgk infusion and assess for neurologic symptoms. Permanently discontinue naxitamab-gqgk in case of symptomatic RPLS.
Peripheral Neuropathy
Peripheral neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, and neuralgia, occurred in 32% of patients in Study 201 and in 25% of patients in Study 12-230. Most signs and symptoms of neuropathy began on the day of the infusion and neuropathy lasted a median of 5.5 days (range 0 to 22 days) in Study 201 and 0 days (range 0 to 22 days) in Study 12-230.
Permanently discontinue naxitamab-gqgk based on severity.
Neurological Disorders of the Eye
Neurological disorders of the eye including unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, and photophobia occurred in 24% of patients in Study 201 and 19% of patients in Study 12-230. Neurological disorders of the eye lasted a median of 17 days (range 0 to 84 days) in Study 201 with two patients (8%) experiencing an event that had not resolved at the time of data cutoff, and a median of 1 day (range less than one day to 21 days) in Study 12-230. Permanently discontinue naxitamab-gqgk based on severity.
Prolonged Urinary Retention
Urinary retention occurred in 1 (4%) patient in Study 201 and in 3 patients (4%) in Study 12-230. All events in both studies occurred on the day of an infusion of naxitamab-gqgk and lasted between 0 and 24 days. Permanently discontinue naxitamab-gqgk in patients with urinary retention that does not resolve following discontinuation of opioids.
Hypertension
Hypertension occurred in 44% of patients in Study 201 and 28% of patients in Study 12-230 who received naxitamab-gqgk. Grade 3 or 4 hypertension occurred in 4% of patients in Study 201 and 7% of patients in Study 12-230. Four patients (6%) in Study 12-230 permanently discontinued naxitamab-gqgk due to hypertension. In both studies, most events occurred on the day of naxitamab-gqgk infusion and occurred up to 9 days following an infusion of naxitamab-gqgk.
Do not initiate naxitamab-gqgk in patients with uncontrolled hypertension. Monitor blood pressure during infusion, and at least daily on Days 1 to 8 of each cycle of naxitamab-gqgk and evaluate for complications of hypertension including RPLS. Interrupt naxitamab-gqgk infusion and resume at a reduced rate, or permanently discontinue naxitamab-gqgk based on the severity.
Embryo-fetal Toxicity
Based on its mechanism of action, naxitamab-gqgk may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential, including pregnant women, of the potential risk to a fetus. Advise females of reproductive potential to use effective contraceptive during treatment with naxitamab-gqgk and for two months after the final dose.
Specific Populations
Pregnancy
Risk Summary: Based on its mechanism of action, naxitamab-gqgk may cause fetal harm when administered to pregnant women. There are no available data on the use of naxitamab-gqgk in pregnant women and no animal reproduction studies have been conducted with naxitamab-gqgk. 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.
Lactation
There are no data on the presence of naxitamab-gqgk in human milk or its effects on the breastfed child, or on milk production, however, human IgG is present in human milk. Because of the potential for serious adverse reactions in a breastfed child from naxitamab-gqgk, advise women not to breastfeed during treatment and for 2 months after the final dose of naxitamab-gqgk.
Females And Males Of Reproductive Potential
Naxitamab-gqgk may cause fetal harm when administered to a pregnant woman.
Verify pregnancy status in females of reproductive potential prior to initiating naxitamab-gqgk.
Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the final dose of naxitamab-gqgk.
Pediatric Use
The safety and effectiveness of naxitamab-gqgk, in combination with GM-CSF for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response or stable disease following prior therapy, have been established in pediatric patients 1 year of age and older.
Safety and effectiveness have not been established in pediatric patients younger than 1 year of age.
Geriatric Use
Neuroblastoma is largely a disease of pediatric and young adult patients. Clinical studies of naxitamab-gqgk in combination with GM-CSF did not include patients 65 years of age and older.
Common Adverse Effects
-
The most common adverse reactions (≥25%) are infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability.
-
The most common grade 3 or 4 laboratory abnormalities (≥5%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.
Drug Interactions
Specific Drugs
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Actions
Mechanism Of Action
Naxitamab-gqgk binds to the glycolipid GD2. GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves. In vitro, naxitamab-gqgk was able to bind to cell surface GD2 and induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).
Advice to Patients
-
Advise the patient and caregiver to read the FDA-approved patient labeling (Patient Information).
-
Advise patients and caregivers that naxitamab-gqgk can cause serious infusion-related reactions and anaphylaxis and to immediately report any signs or symptoms, such as facial or lip swelling, urticaria, or difficulty breathing, that occur during or following the infusion.
-
Advise patients and caregivers that naxitamab-gqgk can cause neurotoxicity, including severe pain, peripheral neuropathy, neurological disorders of the eye, prolonged urinary retention, transverse myelitis, and RPLS. Advise patients to contact their healthcare provider for any new or worsening neurological symptoms.
-
Advise patients and caregivers that naxitamab-gqgk can cause hypertension and to immediately report signs or symptoms of hypertension.
-
Advise females of reproductive potential, including pregnant women, of the potential risk to the fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy and to use effective contraception during treatment with and for 2 months after the final dose of naxitamab-gqgk.
-
Advise women not to breastfeed during treatment with naxitamab-gqgk and for 2 months after the final dose.
Additional Information
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
Concentrate for injection |
40 mg/10 mL |
Danyelza |
Y-mAbs Therapeutics |
AHFS Drug Information. © Copyright 2023, Selected Revisions January 25, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
Reload page with references included
More about naxitamab
- Check interactions
- Side effects
- Dosage information
- During pregnancy
- Drug class: miscellaneous antineoplastics
- Breastfeeding
- En español