naxitamab

nax-IT-a-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

High Alert

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 to prior therapy (in combination with granulocyte-macrophage colony-stimulating factor [GM-CSF]) .

Acts as a glycolipid disialoganglioside (GD2)-binding monoclonal antibody that binds to specific cells in the CNS and peripheral nerves, inducing cell lysis through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.

Therapeutic effects:

Decreased progression of neuroblastoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Metabolized into small peptides.

Half-Life: 8.2 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Contraindicated in:

Severe hypersensitivity;
Uncontrolled hypertension;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential;
Pedi: Children <1 yr (safety and effectiveness not established).

CV: hypertension, peripheral edema, tachycardia

Derm: ↑sweating, erythema multiforme, urticaria

EENT: blurred vision, impaired vision, mydriasis, photophobia, rhinorrhea, unequal pupils

Endo: hyperglycemia, hypoglycemia

F and E: hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia

GI: ↑liver enzymes, constipation, diarrhea, hypoalbuminemia, nausea, vomiting

GU: urinary retention

Hemat: anemia, lymphocytopenia, neutropenia, thrombocytopenia

Local: injection site reaction

Metab: ↓appetite, weight loss

Neuro: anxiety, fatigue, headache, irritability, neuropathic pain, peripheral neuropathy, sedation, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), transverse myelitis

Resp: cough

Misc: fever, infusion reactions, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Drug-drug:

None reported.

IV (Adults ): 3 mg/kg/day (max = 150 mg/day) on Days 1, 3, and 5 of each treatment cycle. Repeat treatment cycle every 4 wk until complete response or partial response; then repeat treatment cycle every 4 wk for 5 cycles. Subsequent treatment cycles may be repeated every 8 wk. Discontinue treatment if disease progression or unacceptable toxicity occurs.

Solution for injection: 4 mg/mL

Monitor closely for signs and symptoms of infusion reactions and hypersensitivity reactions (facial or lip swelling, urticaria, difficulty breathing) during and for ≥2 hr following completion of each infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. If Grade 2 infusion reaction (therapy or infusion interruption indicated but responds promptly to symptomatic treatment [antihistamines, NSAIDs, opioids, IV fluids]; prophylactic medications indicated for ≤24 hr) occurs,↓ naxitamab infusion rate to 50% of previous rate and monitor closely until recovery to Grade ≤ 1. ↑ infusion rate gradually to rate prior to the event as tolerated. If Grade 3 reaction (prolonged [not rapidly responsive to symptomatic medication and/or brief interruption of infusion], recurrence of symptoms following initial improvement, hospitalization indicated for clinical sequelae) occurs, immediately interrupt infusion and monitor closely until recovery to Grade ≤ 2. Resume infusion at 50% of rate prior to the event and ↑ infusion rate gradually to infusion rate prior to the event as tolerated. Permanently discontinue naxitamab in patients not responding to medical intervention. If Grade 4 infusion-related reaction (life-threatening consequences, urgent intervention indicated, or Grade 3 or 4 anaphylaxis) occurs,permanently discontinue naxitamab.
Assess for pain (abdominal pain, bone pain, neck pain, extremity pain) during and following each infusion. Usually begins during infusion and lasts <1 day. If Grade 3 pain (unresponsive to maximum supportive measures) occurs, permanently discontinue naxitamab.
Monitor BP before starting, during infusion and at least daily on Days 1–8 of each cycle. Do not start therapy if patient has uncontrolled hypertension. If Grade 3 hypertension occurs, hold naxitamab or pause infusion until recovery to ≤Grade 2. Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually ↑ to rate prior to onset of symptoms. Permanently discontinue naxitamab in patients not responding to medical intervention or if Grade 4 hypertension occurs.
Assess for symptoms of PRES or transverse myelitis (paresthesia, loss of reflexes without pain, loss of function, sensory loss). If symptoms of PRES or transverse myelitis occur, permanently discontinue naxitamab.
Monitor for symptoms of peripheral neuropathy (numbness, pain, burning, paresthesia in extremities) during therapy. Usually begins during infusion and last 5–6 days. If ≥Grade 2 motor neuropathy or Grade 3 or 4 sensory neuropathy occurs, permanently discontinue naxitamab.
Monitor for signs and symptoms of neurological disorders of the eye (unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, photophobia) during therapy. May last around 17 days. If Grade 2 to 4 resulting in ↓ visual acuity or limiting activities of daily living occurs, hold naxitamab until resolution. If resolved, resume naxitamab at 50% of prior dose; if tolerated without recurrence of symptoms, gradually ↑ to dose prior to onset of symptoms. Permanently discontinue naxitamab if not resolved within 2 wk or upon recurrence or if subtotal or total vision loss occurs.
Monitor for prolonged urinary retention. If persists following discontinuation of opioids, permanently discontinue naxitamab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- May cause ↓ serum potassium, sodium, and albumin. May cause ↑ AST and ALT.
- May cause ↓ lymphocytes, neutrophils, hemoglobin, and platelet count.

Premedications and Supportive Medications: Administer sargramostim (GM-CSF) 250 mcg/m² /day SUBQ, beginning 5 days before naxitamab infusion; then administer 500 mcg/m² /day on Days 1–5. Administer sargramostim ≥1 hr before naxitamab infusion on Days 1, 3, and 5.
Pain Management Prior to and During Infusion: Administer prophylactic medication for neuropathic pain (gabapentin) each day starting 5 days before 1st infusion of naxitamab and through Day 7.
Administer oral opioids 45–60 min before starting each infusion of naxitamab and administer additional IV opioids as needed for breakthrough pain during infusion.
Consider use of ketamine for pain that is not adequately controlled by opioids.
Premedication to Risk of Infusion-Related Reactions and Nausea/Vomiting: Administer IV corticosteroids (methylprednisolone 2 mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 min–2 hr before 1st infusion of naxitamab. Administer corticosteroid premedication for subsequent infusions if severe infusion reaction occurred with previous infusion or during the previous cycle.
Administer an antihistamine, an H₂ antagonist, acetaminophen, and an antiemetic 30 min before each infusion.
If a naxitamab dose is missed, administer missed dose the following wk by Day 10. Administer sargramostim (GM-CSF) 500 mcg/m²/day on 1st day of infusion, and on the day before and on the day of the 2nd and 3rd infusion, respectively (total of 5 days with 500 mcg /m²/day).

IV Administration:

Intermittent Infusion: Diluent: Add appropriate quantities of 5% albumin (human) and 0.9% NaCl to an empty, sterile IV infusion bag large enough to hold the volume needed for dose (see manufacturer's instructions). Allow for 5–10 min of passive mixing. Withdraw the required dose of naxitamab and inject into infusion bag containing the 5% albumin (human) and 0.9% NaCl. Discard any unused portion of naxitamab left in vial. Solution is clear to slightly opalescent and colorless to slightly yellow solution; discard solutions that are cloudy, discolored, or contain particulate matter. Solution is stable for up to 8 hr at room temperature or 24 hr if refrigerated. Once removed from refrigeration, infuse within 8 hr.
Rate: Infuse 1st infusion over 60 min. Infuse subsequent infusions over 30–60 min as tolerated. Observe patient for a minimum of 2 hr following each infusion.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Explain the purpose and side effects of naxitamab to patient. Do not stop taking drug without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Patient Information before starting therapy and periodically during therapy in case of changes.
Advise patient to notify health care professional immediately if signs and symptoms of infusion-related reactions (swelling of face, eyes, lips, mouth, or tongue; itching; redness on face [flushing]; rash; hives; trouble breathing; cough; wheezing; noisy, high-pitched breathing; feeling faint or dizzy [low BP]) occur.
Advise patient to notify health care professional if signs and symptoms of severe pain (severe pain in abdomen, bones, neck, legs, arms); inflammation of spinal cord (weakness in legs or arms; bladder and bowel problems; pain in back, legs, or abdomen; numbness; tingling; burning sensation); PRES (severe headache; vision changes; changes in mental status [confusion, disorientation, ↓ alertness], difficulty speaking; weakness in arms or legs; seizures); numbness, tingling, or burning sensation in the arms or legs; nervous system problems of the eye (unequal pupil size, blurred vision, trouble focusing your eyes, dilated pupils, ↓ ability to see, sensitivity to light); or problems urinating or emptying your bladder occur.
Instruct patient to immediately report symptoms of hypertension (sudden or severe headache, elevated BP, blurry vision, chest pain).
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking Rx, OTC, or herbal products.
Rep: May cause fetal harm. Advise female of reproductive potential to use effective contraception and avoid breastfeeding during therapy and for 2 mo after last dose of naxitamab.

Decreased progression of neuroblastoma.

Danyelza

NDC Code

63552- Patheon Manufacturing Services LLC
- 63552-209-
  - 63552-209-00- 120 VIAL in 1 TRAY (63552-209-00) / 10 mL in 1 VIAL

73042- Y-mAbs Therapeutics, Inc.
- 73042-201- DANYELZA
  - 73042-201-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (73042-201-01) / 10 mL in 1 VIAL, SINGLE-DOSE

83266- Patheon Biologics B.V.
- 83266-0000-
  - 83266-0000-0- 10 L in 1 BAG (83266-0000-0)

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