dinutuximab (Rx)

Brand and Other Names:Unituxin
  • Print

Dosing & Uses

AdultPediatric

Not indicated

Dosage Forms & Strengths

solution for injection

  • 17.5mg/5mL (3.5mg/mL)

Neuroblastoma

Indicated in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA) for pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-time multiagent, multimodality therapy

17.5 mg/m2/day IV over 10-20 hr for 4 consecutive days for maximum of 5 cycles

Cycles 1, 3, and 5 (24-day duration): Administer on days 4, 5, 6, and 7

Cycles 2 and 4 (32-day duration): Administer on days 8, 9, 10, and 11

Dosage Modifications

Renal and hepatic impairment: Not studied

Adverse reactions requiring permanent discontinuation

  • Grade 3 or 4 anaphylaxis
  • Grade 3 or 4 serum sickness
  • Grade 3 pain unresponsive to maximum supportive measures
  • Grade 4 sensory neuropathy or grade 3 sensory neuropathy that interferes with daily activities for >2 weeks
  • Grade 2 peripheral motor neuropathy
  • Subtotal or total vision loss
  • Grade 4 hyponatremia despite appropriate fluid management

Dose modifications for selected adverse reactions H4

  • Mild-to-moderate adverse reactions
    • Examples: Transient rash, fever, rigors, localized urticaria
    • Onset of reaction: Reduce at 50% of previous rate; monitor closely
    • After resolution: Gradually increase infusion rate up to maximum rate of 1.75 mg/m2/hr
  • Prolonged or severe adverse reactions
    • Examples: Mild bronchospasm without other symptoms or angioedema that does not affect airway
    • Onset of reaction: Interrupt therapy immediately
    • After resolution: Resume at 50% of previous rate and monitor if signs and symptoms resolve rapidly
    • First recurrence: Discontinue therapy until following day; if symptoms resolve and continued therapy necessary, premedicate with hydrocortisone 1 mg/kg (maximum dose 50 mg) IV and administer dinutuximab at rate of 0.875 mg/m2/hr in an intensive care unit
    • Second recurrence: Permanently discontinue

Capillary leak syndrome

  • Moderate-to-severe but not life-threatening capillary leak syndrome
    • Onset of reaction: Interrupt therapy immediately
    • After resolution: Resume at 50% of previous rate
  • Life-threatening
    • Onset of action: Discontinue therapy for current cycle
    • After resolution: In subsequent cycles, resume at 50% of previous rate
    • First recurrence: Permanently discontinue

Hypotension requiring medical intervention

  • Symptomatic hypotension, systolic blood pressure (SBP) 15% compared with baseline
  • Onset of reaction: Interrupt therapy immediately
  • After resolution: Resume at 50% of previous rate; if blood pressure remains stable for at least 12 hr, increase infusion rate as tolerated to maximum rate of 1.75 mg/m2/hr

Severe systemic infection or sepsis

  • Onset of reaction: Discontinue until infection resolves and proceed with subsequent cycles

Neurological disorder of the eye

  • Onset of reaction: Discontinue until resolution
  • After resolution: Reduce dose by 50%
  • First recurrence or if accompanied by visual impairment: Permanently discontinue

Next:

Adverse Effects

>10%

All grades (dinutuximab/RA)

  • Pain (85%)
  • Thrombocytopenia (66%)
  • Lymphopenia (62%)
  • Infusion reactions (60%)
  • Hypotension (60%)
  • Hyponatremia (58%)
  • Increased ALT (56%)
  • Anemia (51%)
  • Vomiting (46%)
  • Hypokalemia (43%)
  • Diarrhea (43%)
  • Capillary leak syndrome (40%)
  • Neutropenia (39%)
  • Urticaria (37%)
  • Hypoalbuminemia (33%)
  • Increased AST (28%)
  • Hypocalcemia (27%)
  • Hypoxia (24%)
  • Hypophosphatemia (20%)
  • Tachycardia (19%)
  • Hyperglycemia (18%)
  • Sepsis (18%)
  • Pyrexia (17%)
  • Hemorrhage (17%)
  • Hypertriglyceridemia (16%)
  • Device related infection (16%)
  • Proteinuria (16%)
  • Increased serum creatinine (15%)
  • Decreased appetite (15%)
  • Hypertension (14%)
  • Peripheral neuropathy (13%)
  • Hypomagnesemia (12%)

All grades (dinutuximab/GM-CSF)

  • Pain (77%)
  • Thrombocytopenia (62%)
  • Pyrexia (55%)
  • Lymphopenia (54%)
  • Infusion reactions (47%)
  • Hypotension (43%)
  • Increased ALT (43%)
  • Anemia (42%)
  • Diarrhea (37%)
  • Hyponatremia (36%)
  • Vomiting (33%)
  • Hypoalbuminemia (29%)
  • Hypokalemia (26%)
  • Neutropenia (25%)
  • Urticaria (25%)
  • Capillary leak syndrome (22%)
  • Hypocalcemia (20%)
  • Increased AST (16%)

All grades (dinutuximab/IL-2)

  • Pyrexia (65%)
  • Paine (61%)
  • Thrombocytopenia (61%)
  • Lymphopenia (61%)
  • Hyponatremia (55%)
  • Infusion reactions (54%)
  • Hypotension (54%)
  • Increased ALT (48%)
  • Anemia (42%)
  • Hypokalemia (39%)
  • Diarrhea (37%)
  • Capillary leak syndrome (36%)
  • Vomiting (35%)
  • Neutropenia (32%)
  • Urticaria (29%)
  • Hypoalbuminemia (29%)
  • Increased AST (21%)
  • Hypocalcemia (21%)

Grade 3 or 4 (dinutuximab/RA)

  • Pain (51%)
  • Lymphopenia (51%)
  • Pyrexia (40%)
  • Thrombocytopenia (39%)
  • Hypokalemia (37%)
  • Anemia (34%)
  • Neutropenia (34%)
  • Infusion reactions (25%)
  • Hyponatremia (23%)
  • Capillary leak syndrome (23%)
  • Hypotension (16%)

Grade 3 or 4 (dinutuximab/GM-CSF)

  • Pain (43%)
  • Lymphopenia (33%)
  • Thrombocytopenia (31%)
  • Anemia (21%)
  • Neutropenia (19%)
  • Increased ALT (15%)
  • Hypokalemia (13%)
  • Capillary leak syndrome (11%)

Grade 3 or 4 (dinutuximab/IL-2)

  • Lymphopenia (50%)
  • Pyrexia (37%)
  • Pain (35%)
  • Hypokalemia (33%)
  • Thrombocytopenia (33%)
  • Anemia (24%)
  • Neutropenia (28%)
  • Hyponatremia (21%)
  • Capillary leak syndrome (20%)
  • Infusion reactions (20%)
  • Hypotension (16%)
  • Increased ALT (13%)
  • Diarrhea (13%)

1-10%

All grades (dinutuximab/RA)

  • Increased weight (10%)
  • Nausea (10%)

Grade 3 or 4 (dinutuximab/RA)

  • Hemorrhage (6%)
  • Hypertension (2%)

Grade 3 or 4 (dinutuximab/GM-CSF)

  • Pyrexia (10%)
  • Infusion reactions (10%)
  • Urticaria (7%)
  • Diarrhea (6%)
  • Hypotension (5%)
  • Hyponatremia (5%)
  • Increased AST (4%)
  • Hypoalbuminemia (3%)
  • Vomiting (3%)
  • Hypocalcemia (2%)

Grade 3 or 4 (dinutuximab/IL-2)

  • Increased AST (7%)
  • Urticaria (7%)
  • Hypocalcemia (6%)
  • Hypoalbuminemia (5%)
  • Vomiting (2%)

Postmarketing Reports

Neurotoxicity: Prolonged urinary retention, transverse myelitis, and reversible posterior

leukoencephalopathy syndrome

Previous
Next:

Warnings

Black Box Warning

Infusion reactions

  • Serious and potentially life-threatening infusion reactions occurred in 26% of patients
  • Administer required prehydration and premedication, including antihistamines, prior to each dinutuximab infusion
  • Monitor closely for signs and symptoms of an infusion reaction during and for at least 4 hr following completion of each dinutuximab infusion
  • Immediately interrupt therapy for severe infusion reactions and permanently discontinue dinutuximab for anaphylaxis

Neurotoxicity

  • Causes severe neuropathic pain in the majority of patients
  • Administer intravenous opioid prior to, during, and for 2 hr following completion of the infusion
  • In clinical studies of patients with high-risk neuroblastoma, grade 3 peripheral sensory neuropathy occurred in 2-9% of patients
  • In clinical studies of dinutuximab and related GD2-binding antibodies, severe motor neuropathy was observed in adults
  • Resolution of motor neuropathy was not documented in all cases
  • Discontinue for severe unresponsive pain, severe sensory neuropathy, or moderate-to-severe peripheral motor neuropathy

Contraindications

Hypersensitivity

Cautions

Infusion reactions may occur; prior to dinutuximab infusion, administer required intravenous hydration and premedication with antihistamines, analgesics, and antipyretics and monitor for signs and symptoms of infusion reactions during and for at least 4 hr following completion of each infusion in a setting where cardiopulmonary resuscitation medication and equipment is available

Abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal pain, and arthralgia reported in dinutuximab/retinoic acid treated group; premdicate with analgesics, including IV opioids, prior to each dose of dinutuximab and continue until 2 hr following completion of dinutuximab; for severe pain, decrease dinutuximab infusion rate to 0.875 mg/m²/hr; discontinue therapy if pain is not adequately controlled despite infusion rate reduction and institution of maximum supportive measures

Permanently discontinue therapy 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

Immediately interrupt or discontinue therapy and institute supportive management in patients with symptomatic or severe capillary leak syndrome

Closely monitor blood pressure during treatment; immediately interrupt or discontinue therapy and institute supportive management in patients with symptomatic hypotension, systolic blood pressure less than lower limit of normal for age, or systemic blood pressure that is decreased by more than 15% compared with baseline

Monitor patients for signs and symptoms of systemic infection and temporarily discontinue therapy in patients who develop systemic infection until resolution of infection

Interrupt therapy in patients experiencing dilated pupil with sluggish light reflex or other visual disturbances that do not cause visual loss; upon resolution and if continued treatment with therapy is necessary, decrease dinutuximab dose by 50%; permanently discontinue therapy in patients with recurrent signs of eye disorder following dose reduction and patients who experience vision loss

Bone marrow suppression reported; monitor peripheral blood cell counts closely during therapy

Electrolyte abnormalities reported; monitor serum electrolytes daily during therapy

Atypical hemolytic uremic syndrome reported; permanently discontinue therapy and institute supportive management for signs of the syndrome

Advise pregnant women of the potential risk to a fetus; advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of dinutuximab

Urinary retention that persists for weeks to months following discontinuation of opioids reported; permanently discontinue therapy in patients with urinary retention that does not resolve following discontinuation of opioids

Transverse myelitis reported; promptly evaluate any patient with signs or symptoms of transverse myelitis such as weakness, paresthesia, sensory loss, or incontinence; permanently discontinue therapy in patients who develop transverse myelitis

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) reported; institute appropriate medical treatment and permanently discontinue therapy in patients with signs and symptoms of RPLS (e.g., severe headache, hypertension, visual changes, lethargy, or seizures)

Previous
Next:

Pregnancy & Lactation

Pregnancy

Based on mechanism of action, fetal harm may occur when administered to a pregnant female

There are no studies in pregnant females and no reproductive studies in animals to inform the drug-associated risk

Contraception

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

Lactation

No information available on drug presence in human milk, effects on the breastfed infant, or effects on milk production

However, human IgG is present in human milk

Discontinue breastfeeding during treatment

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.

Previous
Next:

Pharmacology

Mechanism of Action

Chimetic monoclonal antibody that binds to the glycolipid disialoganglioside (GD2). GD2 is a glycolipid expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including central nervous system and peripheral nerves

Dinutuximab binds to cell surface GD2 and induces lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity

Absorption

Peak plasma concentration: 11.5 mcg/mL

Distribution

Vd: 5.4 L

Elimination

Half-life: 10 days

Previous
Next:

Administration

IV Compatibilities

0.9% NaCl

IV Preparation

Inspect visually for particulate matter and discoloration prior to administration

Discard if solution is cloudy, has pronounced discoloration, or contains particulate matter

Aseptically withdraw the required volume from the single-use vial and inject into a 100 mL bag of 0.9% NaCl

Mix by gentle inversion; do NOT shake

Discard unused contents of the vial

IV Administration

Verify that patient has adequate hematologic, respiratory, hepatic, and renal function before initiating each dose

Not for administration as IV push or bolus

Initiate at an infusion rate of 0.875 mg/m2/hour for 30 min; gradually increase rate as tolerated to a maximum rate of 1.75 mg/m2/hr

Required pretreatment guidelines

  • IV hydration
    • Infuse 0.9% NaCl 10 mL/kg IV over 1 hr just before each infusion
  • Analgesics
    • Morphine sulfate (50 mcg/kg) IV immediately before infusion; continue as drip at infusion rate of 20-50 mcg/kg/hr during and for 2 hr following completion
    • Administer additional 25-50 mg/kg IV morphine sulfate doses PRN for pain up to once q2hr followed by increase in morphine sulfate infusion rate in clinically stable patients
    • May use fentanyl or hydromorphone if morphine sulfate not tolerated
    • If pain inadequately managed with opioids, consider use of gabapentin or lidocaine in conjunction with IV morphine
  • Antihistamines and antipyretics
    • Administer antihistamine (eg, diphenhydramine 0.5-1 mg/kg IV; not to exceed 50 mg IV over 10-15 min) starting 20 min before infusion and as tolerated q4-6hr during infusion
    • Administer acetaminophen 10-15 mg/kg; not to exceed 650 mg 20 min before each infusion and q4-6hr PRN for fever or pain
    • Administer ibuprofen 5-10 mg/kg q6hr PRN for control of persistent fever or pain

Storage

Vials

  • Refrigerate at 2-8ºC (36-46ºF) in the outer carton to protect from light until time of use
  • Do not freeze or shake the vial

Diluted infusion bag

  • Refrigerate at 2-8ºC (36-46ºF) ; initiate infusion within 4 hr of preparation
  • Discard bag 24 hr after preparation
Previous
Next:

Images

Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

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.
QL Quantity Limits
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.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous
Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.