naxitamab (Rx)

Brand and Other Names:Danyelza, naxitamab-gqgk
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, solution

  • 40mg/10mL (4mg/mL) single-dose vial

Neuroblastoma

Indicated, in combination with granulocyte macrophage colony-stimulating factor (GM-CSF), for relapsed or refractory high-risk neuroblastoma in the bone or bone marrow in patients who have demonstrated a partial response, minor response, or stable disease with prior therapy

GM-CSF 250 mcg/m2/day SC on Days -4 to 0, beginning 5 days before infusion

GM-CSF 500 mcg/m2/day SC Days 1 to 5; administer 1 hr before administration

Naxitamab 3 mg/kg/day (up to 150 mg/day) IV on Days 1, 3, and 5; repeat q4Weeks until complete response or partial response, followed by 5 additional cycles q4Weeks

Then repeat q8Weeks for subsequent cycles thereafter

Discontinue naxitamab and GM-CSF for disease progression or unacceptable toxicity

Dosage Modifications

Infusion-related reactions

  • Grade 2
    • Infusion interruption indicated, but responds promptly to symptomatic treatment (eg, antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hr
    • Reduce to 50% of previous rate until recovery to Grade ≤1and monitor closely; gradually increase as tolerated to rate before the event
  • Grade 3
    • Prolonged (eg, delayed response to symptomatic medication and/or interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae
    • Immediately interrupt infusion until recovery to Grade ≤2 and monitor closely
    • Resume at 50% of the rate before the event; gradually increase as tolerated to rate before the event
    • Permanently discontinue if nonresponsive to medical intervention
  • Grade 4
    • Life-threatening consequences (eg, urgent intervention indicated) or Grade 3 or 4 anaphylaxis
    • Permanently discontinue

Pain

  • Grade 3 unresponsive to maximum supportive measures
  • Permanently discontinue

Reversible posterior leukoencephalopathy syndrome (RPLS)

  • All grades: Permanently discontinue

Transverse myelitis

  • All grades: Permanently discontinue

Peripheral neuropathy

  • Grade ≥2 motor neuropathy or Grade 3 or 4 sensory neuropathy
  • Permanently discontinue

Neurological disorders of the eye

  • Grade 2-4
    • Resulting in decreased visual acuity or limiting activities of daily living
    • Withhold until resolution; resume at 50% of the prior dose once resolved
    • If tolerated without recurrence of symptoms, gradually increase to dose prior to onset of symptoms
    • Permanently discontinue if unresolved within 2 weeks or upon recurrence
  • Subtotal or total vision loss
    • Permanently discontinue

Prolonged urinary retention

  • Persisting following discontinuation of opioids: Permanently discontinue

Hypertension

  • Grade 3
    • Withhold or pause infusion until recovery to Grade ≤2
    • Resume at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase to rate prior to onset of symptoms
    • Permanently discontinue if nonresponsive to medical intervention
  • Grade 4
    • Permanently discontinue

Other adverse reactions

  • Grade 3
    • Withhold until recovery to Grade ≤2, then resume at same rate
    • Permanently discontinue if not resolved to Grade ≤2 within 2 weeks
  • Grade 4
    • Permanently discontinue

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

Dosage Forms & Strengths

injection, solution

  • 40mg/10mL (4mg/mL) single-dose vial

Neuroblastoma

Indicated, in combination with granulocyte macrophage colony-stimulating factor (GM-CSF), for patients aged >1 year with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease with prior therapy

<1 year: Safety and efficacy not established

≥1 year

  • GM-CSF 250 mcg/m2/day SC on Days -4 to 0, beginning 5 days before infusion
  • GM-CSF 500 mcg/m2/day SC Days 1 to 5; administer 1 hr before administration
  • Naxitamab 3 mg/kg/day (up to 150 mg/day) IV on Days 1, 3, and 5; repeat q4Weeks until complete response or partial response, followed by 5 additional cycles q4Weeks
  • Then repeat q8Weeks for subsequent cycles thereafter
  • Discontinue naxitamab and GM-CSF for disease progression or unacceptable toxicity

Dosage Modifications

Infusion-related reactions

  • Grade 2
    • Infusion interruption indicated, but responds promptly to symptomatic treatment (eg, antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hr
    • Reduce to 50% of previous rate until recovery to Grade ≤1and monitor closely; gradually increase as tolerated to rate before the event
  • Grade 3
    • Prolonged (eg, delayed response to symptomatic medication and/or interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae
    • Immediately interrupt infusion until recovery to Grade ≤2 and monitor closely
    • Resume at 50% of the rate before the event; gradually increase as tolerated to rate before the event
    • Permanently discontinue if nonresponsive to medical intervention
  • Grade 4
    • Life-threatening consequences (eg, urgent intervention indicated) or Grade 3 or 4 anaphylaxis
    • Permanently discontinue

Pain

  • Grade 3 unresponsive to maximum supportive measures
  • Permanently discontinue

Reversible posterior leukoencephalopathy syndrome (RPLS)

  • All grades: Permanently discontinue

Transverse myelitis

  • All grades: Permanently discontinue

Peripheral neuropathy

  • Grade ≥2 motor neuropathy or Grade 3 or 4 sensory neuropathy
  • Permanently discontinue

Neurological disorders of the eye

  • Grade 2-4
    • Resulting in decreased visual acuity or limiting activities of daily living
    • Withhold until resolution; resume at 50% of the prior dose once resolved
    • If tolerated without recurrence of symptoms, gradually increase to dose prior to onset of symptoms
    • Permanently discontinue if unresolved within 2 weeks or upon recurrence
  • Subtotal or total vision loss
    • Permanently discontinue

Prolonged urinary retention

  • Persisting following discontinuation of opioids: Permanently discontinue

Hypertension

  • Grade 3
    • Withhold or pause infusion until recovery to Grade ≤2
    • Resume at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase to rate prior to onset of symptoms
    • Permanently discontinue if nonresponsive to medical intervention
  • Grade 4
    • Permanently discontinue

Other adverse reactions

  • Grade 3
    • Withhold until recovery to Grade ≤2, then resume at same rate
    • Permanently discontinue if not resolved to Grade ≤2 within 2 weeks
  • Grade 4
    • Permanently discontinue

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

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Adverse Effects

>10% (naxitamab + GM-CSF)

All grades

  • Pain (94-100%)
  • Infusion-related reaction (94-100%)
  • Tachycardia (44-84%)
  • Decreased lymphocytes (74-79%)
  • Decreased hemoglobin (48-76%)
  • Increased glucose (74%)
  • Decreased neutrophils (61-72%)
  • Decreased platelets (65-71%)
  • Decreased albumin (50-68%)
  • Decreased calcium (64%)
  • Decreased potassium (47-63%)
  • Vomiting (60-63%)
  • Cough (57-60%)
  • Nausea (56-57%)
  • Diarrhea (50-56%)
  • Increased ALT (42-55%)
  • Decreased magnesium (54%)
  • Decreased appetite (16-53%)
  • Increased AST (49%)
  • Decreased phosphate (47%)
  • Hypertension (28-44%)
  • Fatigue (28-44%)
  • Decreased sodium (29-38%)
  • Erythema multiforme (33%)
  • Urticaria (32%)
  • Peripheral neuropathy (25-32%)
  • Decreased glucose (29%)
  • Injection site reaction (28%)
  • Edema (2.8-28%)
  • Pyrexia (11-28%)
  • Headache (18-28%)
  • Anxiety (12-26%)
  • Localized edema (25%)
  • Irritability (25%)
  • Rhinorrhea (15-24%)
  • Depressed level of consciousness (24%)
  • Neurological disorders of the eye (19-24%)
  • Hyperhidrosis (17%)
  • Constipation (15%)
  • Oropharyngeal pain (15%)
  • Breath sounds abnormal (15%)
  • Contusion (15%)
  • Lethargy (14%)
  • Rhinovirus infection (12-14%)
  • Enterovirus infection (13%)
  • Anaphylactic reaction (12%)
  • Influenza (12%)
  • Upper respiratory tract infection (12%)
  • Weight decreased (12%)
  • Erythema (11%)

Grades 3 or 4

  • Pain (2.8-72%)
  • Infusion-related reaction (32-68%)
  • Decreased lymphocytes (30-56%)
  • Decreased neutrophils (39-46%)
  • Decreased hemoglobin (4-42%)
  • Decreased platelets (17-40%)
  • Decreased potassium (8-32%)
  • Depressed level of consciousness (16%)
  • Anaphylactic reaction (12%)

1-10% (naxitamab + GM-CSF)

All grades

  • Peripheral edema (8.3%)
  • Apnea (4.2%)
  • Device-related infection (4.2%)
  • Hypopnea (2.8%)

Grades 3 or 4

  • Increased ALT (8-9%)
  • Decreased glucose (8%)
  • Diarrhea (4.2-8%)
  • Headache (8%)
  • Decreased calcium (8%)
  • Decreased albumin (7%)
  • Hypertension (4-7%)
  • Decreased sodium (6%)
  • Decreased phosphate (5%)
  • Decreased appetite (4.2%)
  • Vomiting (2.8-4%)
  • Urticaria (4%)
  • Tachycardia (1.4-4%)
  • Increased AST (4%)
  • Nausea (1.4%)

Postmarketing Reports

Neurological: Transverse myelitis

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Warnings

Serious Infusion-Related Reactions

Serious infusion reactions can occur, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor

Premedicate before each infusion as recommended and monitor for at least 2 hr following completion of each infusion

Reduce rate, interrupt infusion, or permanently discontinue based on severity

Neurotoxicity

Severe neurotoxicity reported, including severe neuropathic pain, transverse myelitis, and RPLS

Premedicate to treat neuropathic pain as recommended

Permanently discontinue based on the adverse reaction and severity

Contraindications

Severe hypersensitivity; including anaphylaxis to naxitamab

Cautions

Serious infusion reactions may occur requiring urgent intervention, including fluid resuscitation, administration of bronchodilators and corticosteroids, intensive care unit admission, infusion rate reduction, or interruption of infusion

May cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and RPLS

Hypertension reported; do not initiate in patients with uncontrolled hypertension; monitor blood pressure during infusion and at least daily on Days 1-8 of each cycle

Fetal harm may occur when administered to pregnant females

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Pregnancy & Lactation

Pregnancy

Based on its mechanism of action, fetal harm may occur when administered to pregnant females

No data available on use in pregnant females and no animal reproduction studies have been conducted

IgG1 monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during third trimester

Advise pregnant females of potential risk to fetus

Verify pregnancy status in females of reproductive potential before initiation

Contraception

  • Females of reproductive potential: Use effective contraception during treatment and for 2 months after the final dose

Lactation

There are no data on drug presence in human milk or its effects on the breastfed children, or on milk production

However, human IgG is present in human milk

Advise women not to breastfeed during treatment and for 2 months after the final dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Humanized anti-GD2 3F8 monoclonal antibody; stimulates antibody-dependent cell-mediated cytotoxicity against GD2-expressing tumor cells

GD2, a disialoganglioside with expression in normal tissues restricted primarily to the cerebellum and peripheral nerves, is commonly expressed at high levels on tumors of neuroectodermal origins such as melanomas and neuroblastomas

Absorption

Peak plasma concentration: 57.4 mcg/mL

Metabolism

Expected to be metabolized into small peptides by catabolic pathways

Elimination

Half-life: 8.2 days

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Administration

IV Preparation

Visually inspect vial for particulate matter and discoloration before use; solution should appear clear to slightly opalescent and colorless to slightly yellow; discard if solution is discolored, cloudy, or contains particulate matter

Add appropriate quantities of 5% albumin (human) and 0.9% NaCl injection into an empty, sterile IV infusion bag large enough to hold total infusion volume (refer to prescribing information)

Allow for 5-10 min of passive mixing

Withdraw required dose and inject into infusion bag containing the 5% albumin (human) and 0.9% NaCl; discard any unused drug left in vial

Premedication

Pain management

  • Initiate prophylactic medication for neuropathic pain (eg, gabapentin) on Days -4 through 7
  • Administer oral opioids 45-60 min before initiating each infusion and additional IV opioids PRN for breakthrough pain during infusion
  • Consider ketamine if pain is not adequately controlled by opioids

Prevention of infusion-related reactions and nausea/vomiting

  • Administer IV corticosteroids (eg, methylprednisolone 2 mg/kg [up to 80 mg] or equivalent corticosteroid dose) 30 min to 2 hr before first infusion
  • For subsequent infusions, administer corticosteroids if severe infusion reaction occurred with previous infusion or during previous cycle
  • Administer antihistamine, H2 antagonist, acetaminophen, and antiemetic 30 min before each infusion

IV Administration

Administer as diluted IV infusion as recommended; do not administer as IV push or bolus

First infusion (Cycle 1, Day 1): Infuse over 60 min

Subsequent infusion: Infuse over 30-60 min, as tolerated

Following each infusion: Observe patients for at least 2 hr

Missed dose

  • Administer missed dose the following week by Day 10
  • Administer GM-CSF 500 mcg/m2/day on the first day of infusion, the day before and the day of the second and third infusion (total of 5 days)

Storage

Unopened vials

  • Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light until time of use

Diluted infusions

  • If not used immediately, store at room temperature (15-25ºC [59-77ºF]) for up to 8 hr or refrigerate (2-8ºC [36- 46ºF]) for up to 24 hr
  • Once removed from refrigeration, initiate infusion within 8 hr
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.