(din ue TUX i mab)
- MOAB Ch14.18
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Unituxin: 17.5 mg/5 mL (5 mL) [contains mouse (murine) and/or hamster protein]
Brand Names: U.S.
- Antineoplastic Agent, Anti-GD2
- Antineoplastic Agent, Monoclonal Antibody
Dinutuximab binds to the disialoganglioside GD2, which is highly expressed in neuroblastoma, most melanomas, and other tumors, as well as on normal tissues such as neurons, skin melanocytes, and peripheral sensory nerve fibers (Yu, 2010). By binding to CD2, dinutuximab induces cell lysis (of GD2-expressing cells) through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
Pediatric: 5.4 L
Terminal: 10 days
Use: Labeled Indications
Neuroblastoma: Treatment of high-risk neuroblastoma (in combination with granulocyte-macrophage colony-stimulating factor [GM-CSF; sargramostim], interleukin-2 [IL-2; aldesleukin] and 13-cis-retinoic acid [RA; isotretinoin]) in pediatric patients who achieve at least a partial response to prior first-line multiagent, multimodality therapy.
History of anaphylaxis to dinutuximab
Neuroblastoma, high-risk: IV: 17.5 mg/m2/day for 4 consecutive days for a maximum of 5 cycles (in combination with GM-CSF [sargramostim], IL-2 [aldesleukin] and 13-cis-retinoic acid [isotretinoin]). Infuse on days 4, 5, 6, and 7 during cycles 1, 3, and 5 (cycles 1, 3, and 5 are 24 days in duration); infuse on days 8, 9, 10, and 11 during cycles 2 and 4 (cycles 2 and 4 are 32 days in duration).
Analgesics: Administer morphine 50 mcg/kg IV immediately prior to dinutuximab infusion initiation; continue as a morphine drip at an infusion rate of 20 to 50 mcg/kg/hour during and for 2 hours following completion of infusion. May administer additional doses of 25 to 50 mcg/kg IV as needed up to once every 2 hours followed by an increase in the drip rate in clinically stable patients. Consider conversion to fentanyl or hydromorphone if morphine is not tolerated; if pain is inadequately controlled with opioids, consider adjunct therapy with gabapentin or lidocaine.
Antiemetics: Dinutuxumab is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.
Antihistamine: Administer an antihistamine (eg, diphenhydramine 0.5 to 1 mg/kg/dose; maximum dose 50 mg) IV over 10 to 15 minutes starting 20 minutes prior to dinutuximab infusion and every 4 to 6 hours as tolerated during the infusion.
Antipyretics: Administer acetaminophen (10 to 15 mg/kg/dose; maximum dose 650 mg) 20 minutes prior to each infusion and every 4 to 6 hours as needed for fever and pain. May administer ibuprofen (5 to 10 mg/kg/dose) every 6 hours as needed for control of persistent fever or pain.
IV hydration: Administer NS 10 mL/kg IV over 1 hour just prior to each dinutuximab infusion.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosing: Adjustment for Toxicity
Anaphylaxis, grade 3 or 4: Permanently discontinue therapy.
Capillary leak syndrome:
Moderate to severe, but not life-threatening: Immediately interrupt infusion; upon resolution, resume infusion at 50% of the previous rate.
Life-threatening: Discontinue infusion for the current cycle; in subsequent cycles, infuse at 50% of the previous rate. If life-threatening capillary leak syndrome recurs, permanently discontinue therapy.
Hemolytic uremic syndrome: Permanently discontinue therapy and administer supportive management.
Hyponatremia, grade 4 (despite appropriate fluid management): Permanently discontinue therapy.
Hypotension (symptomatic hypotension, systolic blood pressure [SBP] less than lower limit of normal for age, or SBP decreased by more than 15% compared to baseline): Interrupt infusion; upon resolution, resume infusion at 50% of the previous rate. If blood pressure remains stable for ≥2 hours, increase infusion rate as tolerated up to a maximum rate of 1.75 mg/m2/hour.
Infection (systemic)/sepsis, severe: Discontinue therapy until infection resolves; may resume therapy with subsequent cycles.
Mild to moderate reaction (eg, transient rash, fever, rigors, and localized urticaria that respond promptly to symptomatic treatment): Reduce infusion rate by 50%; monitor closely. Upon resolution, gradually increase infusion rate up to a maximum of 1.75 mg/m2/hour.
Severe or prolonged reaction (eg, mild bronchospasm without other symptoms, angioedema that does not affect the airway): Immediately interrupt infusion; if symptoms resolve rapidly, resume infusion at 50% of the previous rate and monitor closely. If reaction recurs, discontinue therapy until the following day. If symptoms resolve and further treatment is warranted, premedicate with IV hydrocortisone 1 mg/kg (maximum: 50 mg) and infuse at a rate of 0.875 mg/m2/hour in an intensive care unit. If reaction recurs again, permanently discontinue therapy.
Life-threatening reaction: Permanently discontinue therapy and administer supportive management.
Grade 4 sensory neuropathy or grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks: Permanently discontinue therapy.
Grade 2 peripheral motor neuropathy: Permanently discontinue therapy.
Ocular neurological disorders (eg, blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and/or papilledema): Discontinue infusion until symptom resolution; upon resolution, reduce dose by 50%. If reaction recurs, or if reaction is accompanied by visual impairment (eg, subtotal or total vision loss), permanently discontinue therapy.
Pain, severe (grade 3): Decrease the infusion rate to 0.875 mg/m2/hour. If pain is not adequately controlled despite rate reduction and use of maximum supportive measures, permanently discontinue therapy.
Serum sickness, grade 3 or 4: Permanently discontinue therapy.
Must be diluted prior to infusion. Withdraw the required dinutuximab volume and inject into a 100 mL bag of NS. Mix by gentle inversion; do not shake. Discard unused vial contents. Initiate infusion within 4 hours of preparation. Do not use if cloudy, discolored (pronounced), or contains particulates.
Dinutuxumab is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.
Administer as an IV infusion only; do not administer as an IV push or bolus. Administer NS 10 mL/kg IV over 1 hour just prior to each dinutuximab infusion. Premedicate with analgesics, an antihistamine, and an antipyretic prior to administration (see Dosing). Infuse in an environment equipped to monitor for and manage infusion reactions. Interrupt infusion for toxicity (see Dosage Adjustment for Toxicity).
Initiate infusion at a rate of 0.875 mg/m2/hour for 30 minutes. Increase infusion rate gradually as tolerated to a maximum rate of 1.75 mg/m2/hour to infuse over 10 to 20 hours each day. Monitor patients closely for signs and symptoms of an infusion reaction during and for at least 4 hours following completion of each dinutuximab infusion.
Stable in NS
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Keep the vial in the outer carton to protect from light. Solutions diluted for infusion in NS should be stored at 2°C to 8°C (36°F to 46°F). Initiate infusion within 4 hours of preparation. Discard diluted solution 24 hours after preparation.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Frequency not always defined.
Cardiovascular: Hypotension (60%; grades 3/4: 16%), capillary leak syndrome (40%; grades ≥3: 6% to 23%), tachycardia (19%), edema (17%), hypertension (14%)
Central nervous system: Pain (85%; grades 3/4: 51%), peripheral neuropathy (13%; grades 3/4: 6%)
Dermatologic: Urticaria (37%; grades 3/4: 13%)
Endocrine & metabolic: Hyponatremia (58%; grades 3/4: 23%), hypokalemia (43%), hypoalbuminemia (33%), hypocalcemia (27%), hypophosphatemia (20%), hyperglycemia (18%), hypertriglyceridemia (16%), hypomagnesemia (12%)
Gastrointestinal: Increased serum alanine aminotransferase (56%), vomiting (46%), diarrhea (43%), increased serum aspartate aminotransferase (28%), decreased appetite (15%)
Genitourinary: Proteinuria (16%)
Hematologic & oncologic: Thrombocytopenia (66%; grades 3/4: 39%), lymphocytopenia (62%; grades 3/4: 51%), anemia (51%; grades 3/4: 34%), neutropenia (39%; grades 3/4: 34%), hemorrhage (17%; grades 3/4: 6%), febrile neutropenia (grades 3/4: 4%)
Infection: Sepsis (18%; grade 3/4: 16%), infection (device related, 16%; grade 3/4: 16%), bacteremia (grades 3/4: 13%)
Renal: Increased serum creatinine (15%)
Respiratory: Hypoxia (24%)
Miscellaneous: Fever (72%; grades 3/4: 40%), infusion related reaction (60%)
1% to 10%
Central nervous system: Peripheral sensory neuropathy (9%; grade 3: 1%), peripheral motor neuropathy (grade 3: 1%)
Endocrine & metabolic: Weight gain (10%), electrolyte disturbance
Gastrointestinal: Nausea (10%)
Hematologic & oncologic: Hemolytic-uremic syndrome (2%)
Hypersensitivity: Severe infusion related reaction
Ophthalmic: Blurred vision (2%), blepharoptosis, optic nerve damage, papilledema, photophobia
Renal: Renal insufficiency
<1% (Limited to important or life-threatening): Diplopia, fixation of pupils, mydriasis
Concerns related to adverse effects:
• Bone marrow suppression: Severe (grade 3 or 4) anemia, neutropenia, thrombocytopenia, and neutropenic fever were observed in dinutuximab-treated patients. Monitor complete blood counts closely during treatment.
• Capillary leak syndrome: Severe capillary leak syndrome was reported in close to one-fourth of patients receiving dinutuximab. Immediately interrupt infusion if capillary leak syndrome develops; infusion rate reduction and/or therapy discontinuation may be necessary. Initiate appropriate management in patients with symptomatic or severe capillary leak syndrome.
• Electrolyte abnormalities: Electrolyte abnormalities (such as hyponatremia, hypokalemia, and hypocalcemia) were reported in at least one-fourth of patients who received dinutuximab, including grade 3 or 4 events. In a study of a related anti-GD2 antibody, syndrome of inappropriate antidiuretic hormone secretion (SIADH) resulting in severe hyponatremia was reported. Monitor electrolytes closely during therapy.
• Gastrointestinal toxicity: Dinutuxumab is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting.
• Hemolytic uremic syndrome: Hemolytic uremic syndrome (without documented infection) resulted in renal insufficiency, electrolyte abnormalities, anemia, and hypertension in a small number of patients. Atypical hemolytic uremic syndrome recurred in one patient upon rechallenge. Permanently discontinue if hemolytic uremic syndrome develops; manage supportively.
• Hypotension: Severe hypotension occurred more frequently in patients receiving dinutuximab. Intravenous hydration is required prior to each infusion; closely monitor blood pressure during infusion. May require therapy interruption or discontinuation; initiate appropriate medical management in patients with a systolic blood pressure (SBP) less than lower limit of normal for age, or SBP that is decreased by more than 15% compared to baseline.
• Infection: Severe (grade 3 or 4) bacteremia was reported more frequently in dinutuximab-treated patients, and required intravenous antibiotics or other urgent interventions. Sepsis was also observed in patients receiving dinutuximab. Monitor closely for signs/symptoms of systemic infection; may require therapy interruption until resolution of infection.
• Infusion reaction: [US Boxed Warning]: Serious and potentially life-threatening infusion reactions occurred in approximately one-fourth of patients treated with dinutuximab. Administer required prehydration and premedication, including antihistamines, prior to each dinutuximab infusion. Monitor patients closely for signs and symptoms of an infusion reaction during and for at least 4 hours following completion of each dinutuximab infusion. Immediately interrupt dinutuximab for severe infusion reactions and permanently discontinue dinutuximab for anaphylaxis. Infusion reactions typically occurred during infusion or within 24 hours of completion and may include facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, and hypotension. Infusion reactions may require blood pressure support, bronchodilator therapy, corticosteroids, infusion rate interruption and/or reduction, or permanent therapy discontinuation. Infusion should be in a facility with cardiopulmonary medication/equipment available.
• Ocular toxicity: Neurological ocular toxicity such as blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, and papilledema were reported in clinical trials. In patients who experienced complete resolution of ocular toxicity, the median duration of toxicity was 4 days (range: 0 to 221 days). May require therapy interruption, dosage reduction, or treatment discontinuation.
• Pain: Most patients experienced pain; severe pain was observed in over 50% of patients treated with dinutuximab; pain may occur despite analgesic/opioid therapy. Pain typically occurred during infusion and included abdominal, generalized, extremity, or back pain, neuralgia, musculoskeletal chest pain, and arthralgia. Premedication with analgesics, including opioids, is required prior to each dose, during the infusion, and for 2 hours following the infusion. Severe pain may require reduction of the infusion rate or therapy discontinuation.
• Peripheral neuropathy: [US Boxed Warning]: Dinutuximab causes severe neuropathic pain in the majority of patients. Administer intravenous opioids prior to, during, and for 2 hours following completion of the dinutuximab infusion. In clinical studies of patients with high-risk neuroblastoma, grade 3 peripheral sensory neuropathy occurred in 2% to 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. Permanently discontinue dinutuximab for severe unresponsive pain, severe sensory neuropathy, or moderate to severe peripheral motor neuropathy. In patients who experienced peripheral sensory neuropathy of any grade, the median duration was 9 days (range: 3 to 163 days).
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
CBC with differential, serum electrolytes, renal function, blood pressure; monitor for signs/symptoms of infusion reactions (during and for at least 4 hours after infusion), pain, peripheral neuropathy, capillary leak syndrome, infection/sepsis, hemolytic uremic syndrome, and ocular toxicity
Reproduction studies have not been completed with dinutuximab. Monoclonal antibodies cross the placenta, the largest amount during the third trimester of pregnancy. Based on the mechanism of action, dinutuximab may cause fetal harm. Women of reproductive potential should use effective contraception during therapy and for 2 months after the last dose.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, lack of appetite, nausea, vomiting, or weight gain. Have patient report immediately to prescriber signs of infusion reaction (chills, dizziness, passing out, fever, itching, angioedema, or trouble breathing), severe pain, burning or numbness feeling, muscle weakness, signs of capillary leak syndrome (abnormal heartbeat; angina; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; unable to pass urine or change in amount of urine passed; or blood in the urine), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or nausea or vomiting), signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of infection, signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), blurred vision, blindness, vision changes, sensitivity to light, dizziness, passing out, tachycardia, loss of strength and energy, pale skin, edema, or severe headache (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about dinutuximab
- Other brands: Unituxin