Version May 2024
Naxitamab can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Infusion reactions of any grade occurred in 94 to 100% of patients. Severe infusion reactions occurred in 32 to 68%, and serious infusion reactions occurred in 4 to 18% of patients in naxitamab clinical studies. Premedicate prior to each naxitamab infusion as recommended, and monitor patients for at least 2 hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue naxitamab based on severity.
Naxitamab can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Pain of any grade occurred in 94 to 100% of patients of patients in naxitamab clinical studies. Premedicate to treat neuropathic pain as recommended. Permanently discontinue naxitamab based on the adverse reaction and severity.
Note: Administer premedications to reduce the risk of infusion-related reactions and nausea/vomiting (naxitamab is associated with nausea and vomiting); administer pain management prior to and during infusion.
Neuroblastoma (high-risk), relapsed or refractory: Children and Adolescents: IV: 3 mg/kg/day (maximum dose: 150 mg/day) on days 1, 3, and 5 of each treatment cycle (in combination with sargramostim [GM-CSF]). Treatment cycles are repeated every 4 weeks until complete or partial response, followed by 5 additional cycles (every 4 weeks). Subsequent cycles may be repeated every 8 weeks. Discontinue for unacceptable toxicity or if patient experiences disease progression.
Premedication: Administer an H1 antagonist antihistamine, an H2 antagonist antihistamine, acetaminophen, and an antiemetic 30 minutes prior to each naxitamab infusion. In addition, administer an IV corticosteroid such as methylprednisolone 2 mg/kg (maximum: 80 mg/dose) or equivalent 30 minutes to 2 hours prior to the first naxitamab infusion. For subsequent infusions, administer systemic corticosteroid if a severe infusion reaction occurred with the previous infusion (or during the previous cycle).
Pain management (prior to and during naxitamab infusion):
Day −4 through Day 7: Administer a 12-day course of a prophylactic medication for neuropathic pain (eg, gabapentin); initiate 5 days (Day −4) prior to the first naxitamab infusion in each cycle.
Prior to and during infusion: Administer oral opioids 45 to 60 minutes prior to initiation of each naxitamab infusion; additional IV opioids may be administered as needed for breakthrough pain during the infusion. If pain is not adequately controlled by opioids, may consider ketamine.
Dosing adjustment for toxicity: Children and Adolescents:
|
Adverse reaction |
Grade |
Dosage modification |
|---|---|---|
|
Hypertension |
Grade 3 |
Withhold naxitamab or interrupt infusion until recovery to ≤ grade 2, then resume infusion at 50% of prior infusion rate. If tolerated (no recurrence of symptoms), gradually increase infusion rate to rate prior to onset of symptoms. Permanently discontinue naxitamab if no response to medical intervention. |
|
Grade 4 |
Permanently discontinue naxitamab. | |
|
Infusion-related reactions |
Grade 2 |
Reduce naxitamab infusion rate to 50% of previous rate. Monitor closely until improvement to ≤ grade 1, then increase infusion rate gradually as tolerated to rate prior to the event. |
|
Grade 3 |
Immediately interrupt naxitamab infusion. Monitor closely until recovery to ≤ grade 2, then resume infusion at 50% of the previous rate and increase infusion rate gradually as tolerated to rate prior to the event. Permanently discontinue naxitamab if no response to medical intervention. | |
|
Grade 4: Life-threatening consequences; urgent intervention indicated or grade 3 or 4 anaphylaxis |
Permanently discontinue naxitamab. | |
|
Ocular (neurologic disorders of the eye) |
Grade 2 to 4 resulting in decreased visual acuity or limiting activities of daily living |
Withhold naxitamab until resolution. If resolved, resume naxitamab at 50% of the prior dose; if tolerated (no recurrence of symptoms), gradually increase naxitamab dose to the dose prior to onset of symptoms. Permanently discontinue naxitamab if not resolved within 2 weeks, or if toxicity recurs. |
|
Subtotal or total vision loss |
Permanently discontinue naxitamab. | |
|
Pain |
Grade 3 (unresponsive to maximum supportive measures) |
Permanently discontinue naxitamab. |
|
Peripheral neuropathy |
Motor neuropathy ≥ Grade 2 |
Permanently discontinue naxitamab. |
|
Sensory neuropathy ≥ Grade 3 | ||
|
Reversible posterior leukoencephalopathy syndrome (RPLS) |
Any |
Permanently discontinue naxitamab. |
|
Transverse myelitis |
Any |
Permanently discontinue naxitamab. |
|
Urinary retention, prolonged |
Persistent despite opioid discontinuation |
Permanently discontinue naxitamab. |
|
Other adverse reaction |
Grade 3 |
Withhold naxitamab until recovery to ≤ grade 2, then resume naxitamab at the same rate. Permanently discontinue naxitamab if not resolved to ≤ grade 2 within 2 weeks. |
|
Grade 4 |
Permanently discontinue naxitamab. |
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Naxitamab: Drug information")
Note: Administer premedications to reduce the risk of infusion-related reactions and nausea/vomiting (naxitamab is associated with nausea and vomiting); administer pain management prior to and during infusion.
Neuroblastoma (high risk), relapsed or refractory:
IV: 3 mg/kg/day (maximum: 150 mg/day per the manufacturer’s labeling) on days 1, 3, and 5 of each 4-week treatment cycle (in combination with sargramostim [GM-CSF]). Note: Treatment cycles are repeated every 4 weeks until complete or partial response, followed by 5 additional cycles (every 4 weeks). Subsequent cycles may be repeated every 8 weeks. Discontinue (naxitamab and GM-CSF) with disease progression or unacceptable toxicity. Refer to sargramostim monograph for GM-CSF dosing.
Premedication: Administer an antihistamine, an H2 antagonist, acetaminophen, and an antiemetic 30 minutes prior to each naxitamab infusion. In addition, administer an IV corticosteroid such as methylprednisolone 2 mg/kg (maximum: 80 mg/dose) or equivalent corticosteroid 30 minutes to 2 hours prior to the first naxitamab infusion. The systemic corticosteroid may be administered for subsequent infusions if a severe infusion reaction occurred with the previous infusion (or during the previous cycle).
Pain management (prior to and during naxitamab infusion):
Day –4 through Day 7: Administer a 12-day course of a prophylactic medication for neuropathic pain (eg, gabapentin); initiate 5 days prior to the first naxitamab infusion in each cycle.
Prior to and during infusion: Administer oral opioids 45 to 60 minutes prior to initiation of each naxitamab infusion; additional IV opioids may be administered, as needed, for breakthrough pain during the infusion. If pain is not adequately controlled by opioids, may consider ketamine.
Missed dose: If a naxitamab dose is missed, administer the missed dose the following week (by day 10 of the cycle). Administer sargramostim (GM-CSF) on the first day of the naxitamab infusion, and on the day before and on the day of the second and third infusion, respectively (for a total of 5 days of the 500 mcg/m2/day sargramostim dose [refer to Sargramostim monograph for details]).
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Bone marrow suppression, including decreased hemoglobin, decreased neutrophils, decreased platelet count, and lymphocytopenia, occurred commonly with naxitamab treatment, including severe grade 3 and 4 events.
Naxitamab commonly causes infusion related reactions and reactions may be severe. Infusion-related reactions included anaphylaxis, hypotension, bronchospasm, stridor, and cardiac arrest. In 2 small clinical trials, infusion reactions of any grade occurred in 94% to 100% of patients; grade 3 and 4 reactions occurred in 32% to 68%, and serious reactions occurred in 4% to 18% of patients. A majority of patients required a reduction in infusion rate and/or interruption of infusion for at least 1 infusion reaction; permanent discontinuation may also be required depending on severity of reaction.
Onset: Rapid; usually within 24 hours of completion of infusion, with most occurring within 30 minutes of initiation of the infusion; reactions were most frequent during the first infusion in each cycle.
Risk factors:
• Infusion rate
Hypertension was commonly observed, frequently as grade 3 and 4 events. Depending on severity, hypertension may warrant withholding or interrupting the infusion, decreasing infusion rate, or permanent discontinuation.
Onset: Varied; while most cases occurred on the day of infusion, some occurred up to 9 days following infusion.
Risk factors:
• Uncontrolled hypertension (do not initiate in these patients)
Naxitamab may cause severe neurotoxicity, including severe neuralgia (or neuropathic pain), transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). Mild and moderate peripheral neuropathy, which included peripheral sensory, motor neuropathy, paresthesia, and neuralgia, were also commonly reported. In addition, neurological ophthalmic disorders, including anisocoria, blurred vision, accommodation disturbance, mydriasis, visual impairment, and photophobia, were commonly observed, with some having a prolonged duration. Neurotoxicities, depending on severity, may warrant infusion interruptions or permanent discontinuations.
Onset: Varied
Neuropathy: Most cases began on the day of infusion and lasted a median of ~6 days (range: 0 to 22 days).
Neurological eye disorders: Onset unknown; events lasted a median of 1 to 17 days (range: 0 to 84 days).
RPLS: Reported cases in clinical trials occurred 2 and 7 days following completion of the first naxitamab cycle.
Pain (of any grade), including abdominal, bone, neck, and extremity pain, occurred in 94% to 100% of patients. Many of the reported cases were severe pain (grade 3 and 4 events). Neuropathic pain also occurs with therapy. Medications for pain management (opioids and an agent for neuropathic pain) are recommended prior to and during infusion.
Onset: Varied; pain (eg, abdominal, bone, neck, and extremity pain) usually began during the infusion and typically lasted a median of <1 day (range: <1 day to 62 days).
Urinary retention, including some cases persisting after discontinuation of opioids, have been observed. Permanent discontinuation may be required for persistent urinary retention.
Onset: Onset was on the day of infusion for all the cases during clinical trials, with a duration of up to 24 days.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF).
>10%:
Cardiovascular: Edema, hypertension, hypotension, sinus tachycardia, tachycardia
Dermatologic: Erythema multiforme, erythema of skin, hyperhidrosis, urticaria
Endocrine & metabolic: Decreased serum albumin, decreased serum calcium, decreased serum glucose, decreased serum magnesium, decreased serum phosphate, decreased serum potassium, decreased serum sodium, increased serum glucose, weight loss
Gastrointestinal: Constipation, decreased appetite, diarrhea, nausea, viral gastrointestinal infection, vomiting
Hematologic & oncologic: Bruise, decreased hemoglobin, decreased neutrophils, decreased platelet count, lymphocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Infection: Influenza
Local: Injection site reaction, localized edema
Nervous system: Anxiety, fatigue, headache, impaired consciousness, irritability, lethargy, pain, peripheral neuropathy
Ophthalmic: Accommodation disturbance, anisocoria, blurred vision, mydriasis, photophobia, visual impairment
Respiratory: Abnormal breath sounds, cough, nasal infection (viral), oropharyngeal pain, rhinorrhea, upper respiratory tract infection
Miscellaneous: Fever, infusion related reaction (including severe infusion related reactions)
1% to 10%:
Cardiovascular: Peripheral edema
Respiratory: Apnea, shallow respiration
Frequency not defined:
Genitourinary: Urinary retention
Hypersensitivity: Anaphylaxis
Immunologic: Antibody development
Nervous system: Neuralgia (severe), reversible posterior leukoencephalopathy syndrome, severe neurotoxicity, transverse myelitis
Respiratory: Bronchospasm, respiratory depression, stridor
History of severe hypersensitivity to naxitamab or any component of the formulation.
Disease-related concerns:
• Hepatitis B virus screening: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Danyelza: Naxitamab-gqgk 4 mg/mL (10 mL)
No
Solution (Danyelza Intravenous)
40 mg/10 mL (per mL): $2,770.88
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Naxitamab may be associated with a moderate emetic potential; administer an antiemetic, prior to each infusion. Administer an H1 antagonist antihistamine , an H2 antagonist antihistamine, and acetaminophen 30 minutes prior to each naxitamab infusion. Administer oral opioids 45 to 60 minutes prior to initiation of each naxitamab infusion; additional IV opioids may be administered as needed for breakthrough pain during the infusion
Parenteral: IV: Infuse the first infusion (day 1, cycle 1) over 60 minutes. For subsequent infusions, administer over 30 to 60 minutes as tolerated. Do not administer as an IV push or bolus. Observe patients for a minimum of 2 hours following each infusion.
Missed dose: If a naxitamab dose is missed, administer the missed dose the following week (by day 10 of the cycle). Administer sargramostim (GM-CSF) on the first day of the naxitamab infusion, and on the day before and on the day of the second and third infusion, respectively (for a total of 5 days of the 500 mcg/m2/day sargramostim dose [refer to sargramostim monograph for details]).
Naxitamab may be associated with a moderate emetic potential; administer an antiemetic prior to each infusion. Administer in a setting where cardiopulmonary resuscitation medication and equipment is available.
IV: Infuse the first infusion (day 1, cycle 1) over 60 minutes. Administer over 30 to 60 minutes as tolerated for subsequent infusions. Do not administer as an IV push or bolus. Observe patients for a minimum of 2 hours following each infusion. Premedication and pain management prior to infusions are required; refer to "Dosing: Adult."
Store intact vials at 2°C to 8°C (36°F to 46°F). Store in the outer carton to protect from light. If not used immediately, solutions diluted for infusion may be stored for up to 8 hours at 15°C to 25°C (59°F to 77°F) or for up to 24 hours at 2°C to 8°C (36°F to 46°F). Initiate infusion within 8 hours of removal from refrigeration.
Treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients who have demonstrated a partial response, minor response, or stable disease to prior therapy (FDA approved in ages ≥1 year and adults).
Note: Indication received accelerated approval based on overall response rate and duration of response in initial trials; continued approval may be contingent upon confirmatory trials.
Sound-alike/look-alike issues:
Naxitamab may be confused with dinutuximab.
High alert medication:
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Evaluate pregnancy status prior to use in patients who may become pregnant.
Patients who may become pregnant should use effective contraception during therapy and for 2 months after the last naxitamab dose.
Naxitamab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Based on the mechanism of action, in utero exposure to naxitamab may cause fetal harm.
Monitor closely for signs/symptoms of infusion reactions (during and for at least 2 hours after infusion completion). Monitor blood pressure during infusion and at least daily on days 1 to 8 of each cycle; monitor for hypertensive complications. Monitor for signs/symptoms of pain, transverse myelitis, reversible leukoencephalopathy syndrome, peripheral neuropathy, urinary retention, and ocular symptoms.
Naxitamab binds to the glycolipid disialoganglioside (GD2), which is highly expressed in neuroblastoma, and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves. By binding to cell surface GD2, naxitamab induces cell lysis (of GD2-expressing cells) through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
Metabolism: Metabolized into small peptides by catabolic pathways.
Half-life elimination: 8.2 days.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
