dinutuximab

di-noo-TUX-i-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies

REMS

High-risk neuroblastoma in patients who have had at least a partial response to previous first-line multiagent, multimodality therapy (in combination with granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-2 [IL-2], and 13-cis-retinoic acid [RA]) .

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 (ADCC) and complement-dependent cytotoxicity (CDC).

Therapeutic effects:

Decreased progression of neuroblastoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: 10 days.

(event-free survival probability)

ROUTE	ONSET	PEAK	DURATION
IV	6 mo	2 yr	unknown

Contraindicated in:

Previous anaphylactic reaction to dinutuximab;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Renal or hepatic impairment;
Rep: Women of reproductive potential;

CV: capillary leak syndrome, hypotension, tachycardia

Derm: urticaria

EENT: neurologic disorders of the eye

F and E: hypocalcemia, hypokalemia, hyponatremia

GI: ↓appetite, ↑liver enzymes, diarrhea, vomiting

GU: proteinuria, urinary retention

Hemat: anemia, lymphopenia, neutropenia, thrombocytopenia, ATYPICAL HEMOLYTIC UREMIC SYNDROME

Metab: ↑weight, hyperglycemia, hypertriglyceridemia, hypoalbuminemia

Neuro: neuropathic pain, reverse posterior leukoencephalopathy syndrome (rpls), peripheral neuropathy, transverse myelitis

Resp: hypoxia

Misc: pain, INFUSION-RELATED REACTIONS

Drug-drug:

↑risk of myelosuppression with other myelosuppressants, antineoplastics and radiation therapy.

IV (Children ): 17.5 mg/m² once daily for 4 consecutive days for up to 5 cycles.

Solution for injection: 3.5 mg/mL

Assess hematologic, respiratory, hepatic, and renal function prior to each course of dinutuximab to determine adequate function.
Monitor for signs and symptoms of infusion reactions during and for at least 4 hrs following completion of infusion. Infusion reactions usually occur during or within 24 hours of completing infusion. For mild to moderate infusion reactions (transient rash, fever, rigors, localized urticaria) that respond promptly to antihistamines or antipyretics, decrease infusion rate to 50% previous rate and monitor closely. After resolution, gradually increase infusion rate up to maximum rate of 1.75 mg/m²/hour. For serious infusion reactions (facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, hypotension) immediately interrupt dinutuximab infusion and institute supportive therapy. If symptoms resolve rapidly, decrease infusion rate to 50% previous rate and monitor closely. For first recurrence of symptoms, discontinue dinutuximab until next day. If symptoms resolve and continued treatment is warranted, premedicate with hydrocortisone 1 mg/kg (maximum dose 50 mg) IV administer dinutuximab at rate of 0.875 mg/m²/hour in an intensive care unit. Discontinue dinutuximab permanently for life-threatening reactions.
Assess pain (abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, arthralgia) frequently during and following therapy. See Implementation for analgesic guidelines.
Assess for signs and symptoms of peripheral neuropathy (lower extremity weakness and inability to ambulate, neurogenic bladder) frequently during therapy. May occur more frequently in adult patients. Permanently discontinue dinutuximab in patients with Grade 2 peripheral motor neuropathy, Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, or Grade 4 sensory neuropathy.
Monitor for signs and symptoms of capillary leak syndrome (severe hypotension, hypoalbuminemia, hemoconcentration). At onset of moderate to severe, but not life threatening symptoms, interrupt dinutuximab infusion; resume infusion at 50% previous rate when symptoms resolve. Then gradually increase infusion rate up to a maximum rate of 1.75 mg/m²/hour. For life-threatening symptoms, discontinue current cycle of dinutuximab. Administer subsequent cycles at 50% of previous rate. Permanently discontinue dinutuximab if symptoms recur.
Monitor BP closely during therapy. Administer required hydration prior to dinutuximab infusion. Interrupt therapy and institute supportive measures if symptomatic hypotension occurs. Resume at 50% infusion rate. If BP remains stable for at least 2 hours, increase infusion rate as tolerated up to a maximum rate of 1.75 mg/m²/hour.
Monitor for signs and symptoms of infection during therapy. If severe systemic infection or sepsis occur, discontinue dinutuximab until resolution of infection, then continue subsequent cycles.
Monitor for neurological disorders of the eye (blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, papilledema) during therapy. Interrupt therapy in patients with dilated pupil with sluggish light reflex or other visual disturbances not causing visual loss. Upon resolution and if continued treatment is warranted, decrease dinutuximab dose by 50%. Permanently discontinue dinutuximab in patients with recurrent signs or symptoms of eye disorder following dose reduction and in patients with loss of vision.
Assess for urinary retention during and periodically following therapy. If urinary retention does not resolve following discontinuation of opioids, permanently discontinue dinutuximab.
Monitor for signs and symptoms of transverse myelitis (weakness, paresthesia, sensory loss, incontinence). If symptoms occur, permanently discontinue dinutuximab.
Assess for signs and symptoms of reverse posterior leukoencephalopathy syndrome (RPLS) (severe headache, hypertension, visual changes, lethargy, seizures). Discontinue dinutuximab if symptoms occur.
Monitor for signs and symptoms of hemolytic uremic syndrome (fatigue, dizziness, fainting, pallor, edema, decreased urine output, hematuria) during therapy. Permanently discontinue dinutuximab and provide supportive therapy if signs occur.

Lab Test Considerations:

Monitor peripheral blood counts.
- Monitor serum electrolytes daily during therapy. May cause hypokalemia, hyponatremia, and hypocalcemia. Discontinue therapy if Grade 4 hyponatremia occurs despite appropriate fluid management.

Pretreatment: Administer 10 mL/kg of 0.9% NaCl as an infusion 1 hr prior to dinutuximab infusion.
Administer 50 mcg/kg morphine immediately before dinutuximab infusion, then continue as morphine drip at infusion rate of 20 to 50 mcg/kg/hour during and for two hrs following completion of dinutuximab infusion. Give additional 25 mcg/kg to 50 mcg/kg IV morphine as needed for pain up to once every 2 hrs followed by an increase in morphine infusion rate in clinically stable patient.
- Consider fentanyl or hydromorphone if morphine not tolerated.
- If pain is inadequately managed with opioids, consider gabapentin or lidocaine in conjunction with IV morphine.
- For severe pain, decrease dinutuximab infusion rate to 0.875 mg/m²/hour. Discontinue dinutuximab permanently if Grade 3 pain unresponsive to maximum supportive measures occurs.
Administer an antihistamine such as diphenhydramine (0.5 to 1 mg/kg; maximum dose 50 mg) IV over 10 to 15 minutes starting 20 min before initiation of dinutuximab and as tolerated every 4 to 6 hours during infusion.
Administer acetaminophen (10 to 15 mg/kg; maximum dose 650 mg) 20 minutes before each dinutuximab infusion and every 4 to 6 hours as needed for fever or pain. Administer ibuprofen (5 to 10 mg/kg) every 6 hours as needed for control of persistent fever or pain.

IV Administration:

Store vials in refrigerator protected from light. Diluent: Withdraw solution from vial and inject into 100 mL of 0.9% NaCl. Mix by gentle inversion; do not shake. Do not administer solutions that are discolored, cloudy, or contain particulate matter. Store diluted solution in refrigerator; administer within 4 hrs and discard after 24 hrs.
Rate: Infuse over 10–20 hrs for 4 consecutive days for a maximum of 5 cycles. Begin with infusion rate of 0.875 mg/m²/hr for 30 min. Gradually increase for a maximum of 1.75 mg/m²/hr as tolerated.

Explain purpose of dinutuximab to patient and caregivers.
Advise patient to notify health care professional if signs and symptoms of infusion reaction (facial or lip swelling, urticaria, difficulty breathing, lightheadedness or dizziness occurring during or within 24 hours after infusion), capillary leak syndrome, hypotension, infection, or hemolytic uremic syndrome occur.
Inform patient and caregiver of risk of pain and peripheral neuropathy. Advise patient to notify health care professional if pain, numbness, tingling, burning, or weakness occur.
Advise patient to notify health care professional if signs and symptoms of neurological eye disorder (blurred vision, photophobia, ptosis, diplopia, unequal pupil size) occur.
Rep: May cause fetal harm. Caution females of reproductive potential to use effective contraception during and for at least 2 mo following therapy. Advise patient to avoid breastfeeding during therapy.

Decreased progression of neuroblastoma.

Unituxin

NDC Code

66302- United Therapeutics Corp.
- 66302-014- Unituxin
  - 66302-014-01- 1 VIAL, SINGLE-USE in 1 BOX (66302-014-01) > 5 mL in 1 VIAL, SINGLE-USE

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