Naxitamab-gqgk (Monograph)

Brand name: Danyelza
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Antineoplastic agent; recombinant humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against glycolipid disialoganglioside (GD2).

Uses for Naxitamab-gqgk

Neuroblastoma

• Used in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow in pediatric patients ≥1 year of age and adult patients who have experienced a partial response, a minor response, or stable disease with prior therapy.

• Accelerated approval based on overall response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory studies.

Naxitamab-gqgk Dosage and Administration

General

Pretreatment Screening

• Measure BP prior to initiation; do not administer to patients with uncontrolled hypertension.

• Verify pregnancy status prior to initiation of naxitamab therapy in females of reproductive potential.

Patient Monitoring

• Monitor for infusion-related reactions during and for ≥2 hours after the completion of each naxitamab infusion; cardiopulmonary resuscitation medication and equipment should be available. If an infusion-related reaction occurs, institute appropriate medical management and reduce the infusion rate, interrupt the infusion, or permanently discontinue naxitamab based on the severity of the reaction.

• Monitor BP during and following each naxitamab infusion; monitor BP at least daily on days 1 through 8 of each treatment cycle and evaluate for complications of hypertension such as reversible posterior leukoencephalopathy (RPLS).

Premedication and Prophylaxis

• Administer a 12-day course of a prophylactic medication for neuropathic pain (e.g., gabapentin) starting 5 days prior to the first infusion in each cycle (day -4 through day 7) and an oral opioid 45–60 minutes prior to the start of each infusion.

• Administer IV opioids as needed for breakthrough pain during infusion; if pain persists despite use of opiate analgesics, consider use of ketamine.

• Administer IV methylprednisolone 2 mg/kg (maximum dose 80 mg) or an equivalent IV corticosteroid 30 minutes to 2 hours prior to the first infusion to minimize the risk of infusion-related reactions. Continue premedication with corticosteroids for subsequent infusions if a patient experiences a severe infusion reaction during a previous infusion or treatment cycle.

• Administer a premedication regimen consisting of an antihistamine, an H₂ antagonist, acetaminophen, and an antiemetic 30 minutes prior to each infusion to reduce the risk of infusion-related reactions and nausea/vomiting.

Administration

Administer by IV infusion (after dilution); do not administer by rapid IV injection, such as IV push or bolus.

Administer infusions on days 1, 3, and 5 of each treatment cycle; repeat treatment cycles every 4 weeks until complete or partial response, followed by 5 additional cycles every 4 weeks. May repeat subsequent cycles every 8 weeks.

Administer sub-Q GM-CSF daily from 5 days prior to naxitamab infusion (day -4) through day 5. On days 1, 3, and 5, administer GM-CSF ≥1 hour prior to naxitamab infusion.

If an infusion is missed, administer the dose the following week by day 10. Administer GM-CSF 500 mcg/m²/day on the first day of the infusion and on the day before and the day of the second and third infusion in the treatment cycle, respectively (i.e., total of 5 days receiving 500 mcg/m²/day).

Vials are for single use only; discard unused portions.

Dilution

Must dilute prior to IV infusion.

Add appropriate quantities of 5% albumin (human) and 0.9% sodium chloride injection based on the calculated naxitamab dose (volume) to an empty, sterile IV bag as directed in the manufacturer’s labeling. Allow passive mixing for 5–10 minutes. Withdraw the required volume of naxitamab-gqgk and add to infusion bag containing the 5% albumin/0.9% sodium chloride solution. Discard any unused portions left in vial.

If immediate administration is not possible, may store the diluted solution at room temperature (15–25°C) for up to 8 hours or at 2–8°C for up to 24 hours. Start the infusion within 8 hours once removed from refrigeration.

Rate of Administration

Administer by IV infusion over 60 minutes for the first infusion (Cycle 1 Day 1) and over 30-60 minutes as tolerated for subsequent infusions.

Dosage

Pediatric Patients

Neuroblastoma

IV

3 mg/kg/day (up to 150 mg/day) on days 1, 3, and 5 of each treatment cycle. Use in combination with sub-Q GM-CSF in each treatment cycle at a dosage of 250 mcg/m²/day on days -4 to 0 and a dosage of 500 mcg/m²/day on days 1 to 5. Refer to the GM-CSF prescribing information for additional dosing information.

Treatment cycles are repeated every 4 weeks until a complete or partial response is achieved, followed by 5 additional 4-week cycles. Subsequent treatment cycles may be repeated every 8 weeks. Continue treatment until disease progression or unacceptable toxicity.

Adults

Neuroblastoma

IV

3 mg/kg/day (up to 150 mg/day) on days 1, 3, and 5 of each treatment cycle. Use in combination with sub-Q GM-CSF in each treatment cycle at a dosage of 250 mcg/m²/day on days -4 to 0 and a dosage of 500 mcg/m²/day on days 1 to 5. Refer to the GM-CSF prescribing information for additional dosing information

Treatment cycles are repeated every 4 weeks until a complete or partial response is achieved, followed by 5 additional 4-week cycles. Subsequent treatment cycles may be repeated every 8 weeks. Continue treatment until disease progression or unacceptable toxicity.

Therapy Modification for Toxicity

Reduction in infusion rate, temporary interruption of infusion, or discontinuance of naxitamab may be necessary if adverse events occur.

Infusion-related Reactions

If a grade 2 infusion-related reaction occurs (i.e., infusion interruption is indicated, but patient responds promptly to symptomatic treatment; prophylactic medications indicated for ≤24 hours), reduce naxitamab infusion rate by 50%. Monitor patient closely until recovery to grade ≤1; infusion rate may be gradually increased to previous rate as tolerated.

If a grade 3 infusion-related reaction occurs (i.e., prolonged reaction [not immediately responsive to symptomatic treatment and/or brief infusion interruption]; recurrence after initial improvement; or hospitalization indicated), immediately interrupt infusion and monitor patient closely until recovery to grade ≤2. Subsequently, resume naxitamab infusion rate at 50% of the previous rate; infusion rate may be gradually increased to the previous rate as tolerated. In cases where the infusion-related reaction does not respond to medical intervention, permanently discontinue naxitamab.

If a grade 4 infusion-related reaction occurs (i.e., urgent intervention indicated [potentially life-threatening]; or grade 3 or 4 anaphylaxis), permanently discontinue naxitamab.

Neurotoxicity

If grade 3 pain that is unresponsive to maximum supportive measures occurs, permanently discontinue naxitamab.

If RPLS of any grade occurs, permanently discontinue naxitamab.

If transverse myelitis of any grade occurs, permanently discontinue naxitamab.

If grade 2 or higher peripheral motor neuropathy or grade 3 or 4 peripheral sensory neuropathy occurs, permanently discontinue naxitamab.

If a grade 2 to 4 neurological disorder of the eye occurs (i.e., decreases visual acuity or limits activities of daily living), temporarily interrupt therapy until resolution. If resolved, naxitamab may be resumed at 50% of the previous dose; if tolerated without recurrence of symptoms, gradually increase back to dose administered prior to the onset of symptoms. Permanently discontinue naxitamab if symptoms do not resolve within 2 weeks or if the adverse effect recurs.

If subtotal or total vision loss occurs, permanently discontinue naxitamab.

If prolonged urinary retention continues following discontinuation of opioid analgesics, permanently discontinue naxitamab.

Hypertension

If grade 3 hypertension occurs, temporarily withhold, or interrupt the infusion and monitor patient closely until recovery to grade ≤2. Subsequently, resume naxitamab infusion rate at 50% of the previous rate; infusion rate may be gradually increased to the previous rate as tolerated. In cases where hypertension does not respond to medical intervention, permanently discontinue naxitamab.

If grade 4 hypertension occurs, permanently discontinue naxitamab.

Other Adverse Effects

If any other grade 3 adverse effect occurs, temporarily withhold until recovery to grade ≤2. Subsequently, resume naxitamab infusion at the previous infusion rate. Permanently discontinue naxitamab if symptoms do not resolve to grade ≤2 within 2 weeks.

If any other grade 4 adverse effect occurs, permanently discontinue naxitamab.

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.

Renal Impairment

No special population dosage recommendations at this time.

Geriatric Use

No special population dosage recommendations at this time.

Cautions for Naxitamab-gqgk

Contraindications

History of severe hypersensitivity reaction to naxitamab-gqgk.

Warnings/Precautions

Warnings

Serious Infusion-related Reactions

Serious infusion reactions (e.g., hypotension, bronchospasm, hypoxia, and stridor) resulting in the need for urgent intervention (e.g., fluid resuscitation, use of bronchodilators and corticosteroids, temporary interruption of the infusion or reduction in the infusion rate, or admission to the ICU) reported. (See Boxed Warning.) Anaphylaxis and grade 4 cardiac arrest reported in clinical trials.

Generally occurs within 24 hours of the completion of naxitamab infusion; most commonly within 30 minutes after start of the infusion. More common during first infusion of neach treatment cycle.

Monitor for infusion-related reactions during and for ≥2 hours following naxitamab infusion; cardiopulmonary resuscitation medication and equipment should be available.

Premedicate with an antihistamine, acetaminophen, H₂ antagonist, and corticosteroid.

Institute appropriate medical management for serious infusion reactions. Reduce infusion rate, interrupt infusion, or permanently discontinue naxitamab based on severity of the reaction.

Neurotoxicity

Severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS), reported. (See Boxed Warning.) Discontinuance of therapy recommended if transverse myelitis or symptomatic RPLS occurs.

Pain (e.g., abdominal pain, bone pain, neck pain, and extremity pain) commonly reported. Generally occurred during the infusion and resolved in less than 1 day.

Premedicate with a prophylactic medication for neuropathic pain (e.g., gabapentin) and oral opioids. Administer IV opioids as needed for breakthrough pain. Discontinuance of therapy may be necessary.

Peripheral neuropathy (e.g., peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, and neuralgia) reported. Most commonly begins on the day of the infusion and lasts a median of 5.5 days. Discontinuance of therapy may be necessary.

Neurological disorders of the eye (e.g., unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, and photophobia) reported. Discontinuance of therapy may be necessary.

Urinary retention reported; in clinical trials, all events occurred on the day of the infusion and lasted between 0–24 days. If prolonged urinary retention continues following discontinuation of opioid analgesics, permanently discontinue naxitamab.

Other Warnings and Precautions

Hypertension

Hypertension reported; most commonly occurs on the day of the infusion, with events reported up to 9 days following the infusion.

Do not administer naxitamab to patients with uncontrolled hypertension.

Monitor BP during each naxitamab infusion and at least daily on days 1 to 8 of each treatment cycle; monitor for complications of hypertension such as RPLS.

Reduce infusion rate, interrupt infusion, or permanently discontinue naxitamab based on the severity of the reaction.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.

Advise females of reproductive potential to use effective contraceptive methods while receiving naxitamab and for 2 months after the last dose.

Specific Populations

Pregnancy

May cause fetal harm. Apprise patients of the potential hazard to the fetus if nataximab is used during pregnancy.

In females of reproductive potential, verify pregnancy status prior to initiation of naxitamab therapy and advise use of effective contraceptive methods while receiving naxitamab and for 2 months after the last dose.

Lactation

Not known whether naxitamab is distributed into human milk, affects milk production, or affects the breast-fed infant. Advise women not to breast-feed while receiving the drug and for 2 months after the last dose.

Pediatric Use

Safety and effectiveness of naxitamab not established in pediatric patients <1 year of age.

Geriatric Use

Safety and effectiveness not established; neuroblastoma primarily affects pediatric and young adult patients.

Hepatic Impairment

Not studied; not expected to be metabolized by hepatic enzymes.

Renal Impairment

Not studied; not expected to be eliminated renally.

Common Adverse Effects

Adverse effects (≥25%): 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, irritability.

Grade 3 or 4 laboratory abnormalities (≥5%): decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, decreased phosphate.

Drug Interactions

Not studied; low potential for drug interactions. Not metabolized by the CYP system or other drug-metabolizing enzymes.

Naxitamab-gqgk Pharmacokinetics

Absorption

Bioavailability

Exposure increases proportionally with increasing dose.

Elimination

Metabolism

Degraded into small peptides through catabolic pathways.

Half-life

8.2 days.

Stability

Storage

Parenteral

Injection concentrate

Unopened vials: 2–8°C. Protect from light; store in the original container until use.

Diluted solution: May store at room temperature (15–25°C) for up to 8 hours or at 2–8°C for up to 24 hours. Once removed from refrigeration, start infusion within 8 hours.

Actions

• Binds glycolipid disialoganglioside (GD2), a glycolipid expressed on cells of neuroectodermal origin, including neuroblasts and central nervous system and peripheral nerves.

• Cell lysis occurs through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).

• Addition of sub-Q GM-CSF enhances granulocyte-mediated ADCC of neuroblastoma cells.

Advice to Patients

• Advise patients and caregivers that infusion-related reactions are expected with naxitamab treatment. Any signs or symptoms of a serious infusion-related reaction or anaphylaxis should be reported immediately; these include facial or lip swelling, urticaria, or difficulty breathing during or following the infusion.

• Advise patients and caregivers that pain is a common adverse effect with naxitamab. More serious neurotoxicity reactions, including severe pain, peripheral neuropathy, neurological disorders of the eye, prolonged urinary retention, transverse myelitis, and reversible posterior leukoencephalopathy syndrome, can occur. Patients should contact their healthcare provider if they experience any new or worsening symptoms.

• Inform patients and caregivers that naxitamab can cause hypertension; instruct patients to monitor and immediately report any signs or symptoms.

• Advise females to inform their clinicians if they are or plan to become pregnant. Apprise patient of the potential hazard to the fetus if used during pregnancy; females of childbearing potential should avoid becoming pregnant. Advise females of reproductive potential to use effective contraception during treatment and for at least 2 months after the last dose of naxitamab.

• Advise women to inform their clinicians if they are or plan to breastfeed. Avoid breastfeeding during naxitamab treatment and for at least 2 months after the last dose.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Naxitamab-gqgk is obtained through specialty distributors.

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