Unituxin

Unituxin is an FDA-registered drug product whose active ingredient is DINUTUXIMAB. It is labelled by United Therapeutics Corporation taken by intravenous and marketed as a human prescription drug product. Identifiers on file: NDC 66302-014, application BLA125516, label effective 20260706. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing DINUTUXIMAB are most often described in connection with: indicated combination, granulocyte-macrophage colony-stimulating, factor gm-csf, interleukin- il-, cis-retinoic acid, treatment pediatric, high-risk neuroblastoma, achieve least. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Unituxin (dinutuximab) is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy [see Clinical Studies (14) ] . Unituxin is a GD2-binding monoclonal antibody indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. ( 1 )

2 DOSAGE AND ADMINISTRATION Verify that patients have adequate hematologic, respiratory, hepatic, and renal function prior to initiating each course of Unituxin [see Clinical Studies (14) ] . Administer required premedication and hydration prior to initiation of each Unituxin infusion [see Dosage and Administration (2.2) ] . 17.5 mg/m 2 /day as a diluted intravenous infusion over 10 to 20 hours for 4 consecutive days for up to 5 cycles. ( 2.1 , 2.4 ) 2.1 Recommended Dose The recommended dose of Unituxin is 17.5 mg/m 2 /day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles (Table 1 and Table 2) [see Dosage and Administration (2.4) and Clinical Studies (14) ] . Initiate at an infusion rate of 0.875 mg/m 2 /hour for 30 minutes. The infusion rate can be gradually increased as tolerated to a maximum rate of 1.75 mg/m 2 /hour. Follow dose modification instructions for adverse reactions [see Dosage and Administration (2.3) ] . Table 1: Schedule of Unituxin Administration for Cycles 1, 3, and 5 Cycle Day 1 through 3 4 5 6 7 8 through 24 Cycles 1, 3, and 5 are 24 days in duration. Unituxin X X X X Table 2: Schedule of Unituxin Administration for Cycles 2 and 4 Cycle Day 1 through 7 8 9 10 11 12 through 32 Cycles 2 and 4 are 32 days in duration. Unituxin X X X X 2.2 Required Pre-treatment Guidelines Intravenous Hydration Administer 0.9% Sodium Chloride Injection, USP 10 mL/kg as an intravenous infusion over 1 hour just prior to initiating each Unituxin infusion. Analgesics Administer morphine sulfate (50 mcg/kg) intravenously immediately prior to initiation of Unituxin and then continue as a morphine sulfate drip at an infusion rate of 20 to 50 mcg/kg/hour during and for 2 hours following completion of Unituxin. Administer additional 25 mcg/kg to 50 mcg/kg intravenous doses of morphine sulfate as needed for pain up to once every 2 hours followed by an increase in the morphine sulfate infusion rate in clinically stable patients. Consider using fentanyl or hydromorphone if morphine sulfate is not tolerated. If pain is inadequately managed with opioids, consider use of gabapentin or lidocaine in conjunction with intravenous morphine. Antihistamines and Antipyretics Administer an antihistamine such as diphenhydramine (0.5 to 1 mg/kg; maximum dose 50 mg) intravenously over 10 to 15 minutes starting 20 minutes prior to initiation of Unituxin and as tolerated every 4 to 6 hours during the Unituxin infusion. Administer acetaminophen (10 to 15 mg/kg; maximum dose 650 mg) 20 minutes prior to each Unituxin 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. 2.3 Dosage Modifications Manage adverse reactions by infusion interruption, infusion rate reduction, dose reduction, or permanent discontinuation of Unituxin (Table 3 and Table 4) [see Warnings and Precautions (5) , Adverse Reactions (6) , and Clinical Studies (14) ] . Table 3: Adverse Reactions Requiring Permanent Discontinuation of Unituxin 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 more than 2 weeks Grade 2 or greater peripheral motor neuropathy Urinary retention that persists following discontinuation of opioids Transverse myelitis Reversible posterior leukoencephalopathy syndrome (RPLS) Subtotal or total vision loss Grade 4 hyponatremia despite appropriate fluid management Atypical hemolytic uremic syndrome Table 4: Dose Modification for Selected Unituxin Adverse Reactions Infusion-related reactions [see Warnings and Precautions (5.1) ] Mild to moderate adverse reactions, such as transient rash, fever, rigors, and localized urticaria, that respond promptly to symptomatic treatment Onset of reaction: Reduce Unituxin infusion rate to 50% of the previous rate and monitor closely. After resolution: Gradually increase infusion rate up to a maximum rate of 1.75 mg/m 2 /hour. Prolonged or severe adverse reactions, such as mild bronchospasm without other symptoms, or angioedema that does not affect the airway Onset of reaction : Immediately interrupt Unituxin. After resolution: If signs and symptoms resolve rapidly, resume Unituxin at 50% of the previous rate and observe closely. First recurrence: Discontinue Unituxin until the following day. If symptoms resolve and continued treatment is warranted, premedicate with hydrocortisone 1 mg/kg (maximum dose 50 mg) intravenously and administer Unituxin at a rate of 0.875 mg/m 2 /hour in an intensive care unit. Second recurrence: Permanently discontinue Unituxin. Neurological disorders of the eye [see Warnings and Precautions (5.2) ] Onset of reaction: Discontinue Unituxin infusion until resolution. After resolution: Reduce the Unituxin dose by 50%. First recurrence or if accompanied by visual impairment: Permanently discontinue Unituxin. Capillary leak syndrome [see Warnings and Precautions (5.3) ] Moderate to severe but not life-threatening capillary leak syndrome Onset of reaction: Immediately interrupt Unituxin. After resolution: Resume Unituxin infusion at 50% of the previous rate. Life-threatening capillary leak syndrome Onset of reaction: Discontinue Unituxin for the current cycle. After resolution: In subsequent cycles, administer Unituxin at 50% of the previous rate. First recurrence: Permanently discontinue Unituxin. 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. requiring medical intervention [see Warnings and Precautions (5.4) ] Onset of reaction: Interrupt Unituxin infusion. After resolution: Resume Unituxin infusion at 50% of the previous rate. If blood pressure remains stable for at least 2 hours, increase the infusion rate as tolerated up to a maximum rate of 1.75 mg/m 2 /hour. Severe systemic infection or sepsis [see Warnings and Precautions (5.5) ] Onset of reaction: Discontinue Unituxin until resolution of infection, and then proceed with subsequent cycles of therapy. 2.4 Instructions for Preparation and Administration Preparation Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light by storing in the outer carton. DO NOT FREEZE OR SHAKE vials. Inspect visually for particulate matter and discoloration prior to administration. Do not administer Unituxin and discard the single-dose vial if the solution is cloudy, has pronounced discoloration, or contains particulate matter. Aseptically withdraw the required volume of Unituxin from the single-dose vial and inject into a 100-mL bag of 0.9% Sodium Chloride Injection, USP. Mix by gentle inversion. Do not shake. Discard unused contents of the vial. Store the diluted Unituxin solution under refrigeration (2°C to 8°C). Initiate infusion within 4 hours of preparation. Discard diluted Unituxin solution 24 hours after preparation. Administration Administer Unituxin as a diluted intravenous infusion only [see Dosage and Administration (2.1) ] . Do not administer Unituxin as an intravenous push or bolus.

4 CONTRAINDICATIONS Unituxin is contraindicated in patients with a history of anaphylaxis to dinutuximab. History of anaphylaxis to dinutuximab. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Serious Infusion Reactions [see Boxed Warning and Warnings and Precautions (5.1) ] Neurotoxicity, including Pain, Peripheral Neuropathy, Neurological Disorders of the Eye, Prolonged Urinary Retention, Transverse Myelitis, and Reversible Posterior Leukoencephalopathy Syndrome [see Boxed Warning and Warnings and Precautions (5.2) ] Capillary Leak Syndrome [see Warnings and Precautions (5.3) ] Hypotension [see Warnings and Precautions (5.4) ] Infection [see Warnings and Precautions (5.5) ] Bone Marrow Suppression [see Warnings and Precautions (5.6) ] Electrolyte Abnormalities [see Warnings and Precautions (5.7) ] Atypical Hemolytic Uremic Syndrome [see Warnings and Precautions (5.8) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.9) ] The most common adverse drug reactions (≥25%) are pain, pyrexia, thrombocytopenia, lymphopenia, infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and hypocalcemia. ( 5 , 6.1 ) The most common serious adverse reactions (≥5%) are infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. ( 5 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact United Therapeutics Corp. at 1-866-458-6479 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in clinical practice. The data described below reflect exposure to Unituxin at the recommended dose and schedule in 1021 patients with high-risk neuroblastoma enrolled in an open-label, randomized (Study 1), or single-arm clinical trials (Study 2 and Study 3). Prior to enrollment, patients received therapy consisting of induction combination chemotherapy, maximum feasible surgical resection, myeloablative consolidation chemotherapy followed by autologous stem cell transplant, and radiation therapy to residual soft tissue disease. Patients received Unituxin in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA). Treatment commenced within 95 days post autologous stem cell transplant in Study 1, within 210 days of autologous stem cell transplant in Study 2, and within 110 days of autologous stem cell transplant in Study 3. Study 1 In a randomized, open-label, multicenter study (Study 1), 134 patients received Unituxin in combination with GM-CSF, IL-2, and RA (Unituxin/RA group), including 109 randomized patients and 25 patients with biopsy-proven residual disease who were non-randomly assigned to receive Unituxin. A total of 106 randomized patients received RA alone (RA group) [see Dosage and Administration (2) and Clinical Studies (14) ] . Patients had a median age at enrollment of 3.8 years (range: 0.94 to 15.3 years), and were predominantly male (60%) and White (82%). In Study 1, adverse reactions of Grade 3 or greater severity were comprehensively collected, but adverse reactions of Grade 1 or 2 severity were collected sporadically and laboratory data were not comprehensively collected. Approximately 71% of patients in the Unituxin/RA group and 77% of patients in the RA group completed planned treatment. The most common reason for premature discontinuation of study therapy was adverse reactions in the Unituxin/RA group (19%) and progressive disease (17%) in the RA group. The most common adverse drug reactions (≥25%) in the Unituxin/RA group were pain, pyrexia, thrombocytopenia, lymphopenia, infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and hypocalcemia. The most common serious adverse reactions (≥5%) in the Unituxin/RA group were infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. Table 5 lists the adverse reactions reported in at least 10% of patients in the Unituxin/RA group for which there was a between group difference of at least 5% (all grades) or 2% (Grade 3 or greater severity). Table 5: Selected Adverse Reactions Occurring in at Least 10% of Patients in the Unituxin/RA Group in Study 1 Adverse Reaction Includes adverse reactions that occurred in at least 10% of patients in the Unituxin/RA group with at least a 5% (All Grades) or 2% (Grades 3 to 5) absolute higher incidence in the Unituxin/RA group compared to the RA group. , Adverse drug reactions were graded using CTCAE version 3.0. Unituxin/RA (N=134) RA (N=106) All Grades (%) Grades 3 to 4 (%) All Grades (%) Grades 3 to 4 (%) General Disorders and Administration Site Conditions Pain Includes preferred terms abdominal pain, abdominal pain upper, arthralgia, back pain, bladder pain, bone pain, chest pain, facial pain, gingival pain, infusion related reaction, musculoskeletal chest pain, myalgia, neck pain, neuralgia, oropharyngeal pain, pain, pain in extremity, and proctalgia. 85 51 16 6 Pyrexia 72 40 27 6 Edema 17 0 0 0 Blood and Lymphatic System Disorders Based on investigator reported adverse reactions. Thrombocytopenia 66 39 43 25 Lymphopenia 62 51 36 20 Anemia 51 34 22 16 Neutropenia 39 34 16 13 Immune System Disorders Infusion reactions 60 25 9 1 Vascular Disorders Hypotension 60 16 3 0 Capillary leak syndrome One Grade 5 adverse reaction. 40 23 1 0 Hemorrhage Includes preferred terms gastrointestinal hemorrhage, hematochezia, rectal hemorrhage, hematemesis, upper gastrointestinal hemorrhage, hematuria, hemorrhage urinary tract, renal hemorrhage, epistaxis, respiratory tract hemorrhage, disseminated intravascular coagulation, catheter site hemorrhage, hemorrhage, and hematoma. 17 6 6 3 Hypertension 14 2 7 1 Metabolism and Nutrition Disorders Hyponatremia 58 23 12 4 Hypokalemia 43 37 4 2 Hypoalbuminemia 33 7 3 0 Hypocalcemia 27 7 0 0 Hypophosphatemia 20 8 3 0 Hyperglycemia 18 6 4 1 Hypertriglyceridemia 16 1 11 1 Decreased appetite 15 10 5 4 Hypomagnesemia 12 2 1 0 Investigations Increased alanine aminotransferase 56 23 31 3 Increased aspartate aminotransferase 28 10 7 0 Increased serum creatinine 15 2 6 0 Increased weight 10 0 0 0 Gastrointestinal Disorders Vomiting 46 6 19 3 Diarrhea 43 13 15 1 Nausea 10 2 3 1 Skin and Subcutaneous Tissue Disorders Urticaria 37 13 3 0 Respiratory, Thoracic and Mediastinal Disorders Hypoxia 24 12 2 1 Cardiac Disorders Tachycardia Includes preferred terms tachycardia and sinus tachycardia. 19 2 1 0 Infections and Infestations Sepsis 18 16 9 9 Device related infection 16 16 11 11 Renal and Urinary Disorders Proteinuria 16 0 3 1 Nervous System Disorders Peripheral neuropathy 13 3 6 0 Table 6 compares the per-patient incidence of selected adverse reactions occurring during cycles containing Unituxin in combination with GM-CSF (Cycles 1, 3, and 5) with cycles containing Unituxin in combination with IL-2 (Cycles 2 and 4). Table 6: Comparison of Adverse Events by Treatment Cycle in the Unituxin/RA Group in Study 1 Preferred Term Includes preferred terms with a per-patient incidence of at least 20% in the Unituxin and RA group for either IL-2 or GM-CSF containing cycles. , Adverse drug reactions were graded using CTCAE version 3.0. All Grades Severe GM-CSF N=134 (%) IL-2 Seven patients who received GM-CSF in Cycle 1 discontinued prior to starting Cycle 2. N=127 (%) GM-CSF N=134 (%) IL-2 N=127 (%) GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-2, interleukin-2; RA, 13-cis-retinoic acid General Disorders and administration site conditions Pyrexia 55 65 10 37 Pain Includes preferred terms abdominal pain, abdominal pain upper, arthralgia, back pain, bladder pain, bone pain, chest pain, facial pain, gingival pain, infusion related reaction, musculoskeletal chest pain, myalgia, neck pain, neuralgia, oropharyngeal pain, pain, pain in extremity, and proctalgia. 77 61 43 35 Blood and Lymphatic System Disorders Based on investigator-reported adverse reactions. Thrombocytopenia 62 61 31 33 Lymphopenia 54 61 33 50 Anemia 42 42 21 24 Neutropenia 25 32 19 28 Immune System Disorders Infusion reactions 47 54 10 20 Vascular Disorders Hypotension 43 54 5 16 Capillary leak syndrome 22 36 11 20 Metabolism and Nutrition Disorders Hyponatremia 36 55 5 21 Hypokalemia 26 39 13 33 Hypoalbuminemia 29 29 3 5 Hypocalcemia 20 21 2 6 Investigations Increased alanine aminotransferase 43 48 15 13 Aspartate aminotransferase increased 16 21 4 7 Gastrointestinal Disorders Diarrhea 31 37 6 13 Vomiting 33 35 3 2 Skin and Subcutaneous Tissue Disorders Urticaria 25 29 7 7 Study 2 and Study 3 Study 2 was a single-arm, multicenter, expanded access trial that enrolled patients with high-risk neuroblastoma (N=783). The reported adverse event profile of Unituxin in Study 2 was similar to that observed in Study 1. Study 3 was a multicenter, single-arm safety study of Unituxin in combination with GM-CSF, IL-2, and RA. In Study 3, adverse events of all CTCAE grades and laboratory data were systematically and comprehensively collected. Of 104 patients enrolled and treated in Study 3, 77% of patients completed study therapy. In general, the adverse reaction profile of Unituxin observed in Study 3 was similar to that observed in Study 1 and Study 2. The following adverse reactions not previously reported in Study 1 were reported in at least 10% of patients in Study 3: nasal congestion (20%) and wheezing (15%). Table 7 provides the per-patient incidence of laboratory abnormalities in Study 3. Table 7: Per-patient Incidence of Selected (≥5% Grade 3 to 4) Laboratory Abnormalities in Study 3 Laboratory Test Laboratory abnormalities with a per-patient incidence of at least 20% (all grades) and at least a 5% per-patient incidence of severe (Grade 3 or 4) laboratory abnormalities. Grade Based on CTCAE version 4.0. All Grades % Grades 3 to 4 % ND, not determined Hematology Anemia 100 46 Neutropenia 99 63 Thrombocytopenia 98 49 Chemistry Hypoalbuminemia 100 8 Hypocalcemia 97 7 Hyponatremia 93 36 Hyperglycemia 87 6 Aspartate Aminotransferase Increased 84 8 Alanine Aminotransferase Increased 83 13 Hypokalemia 82 41 Hypophosphatemia 78 6 Urinalysis Urinalysis results were reported as positive or negative without assessment of grade. Urine protein 66 ND Red blood cell casts 38 ND 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Unituxin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neurotoxicity: prolonged urinary retention, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2) ] .

What is Unituxin used for?
1 INDICATIONS AND USAGE Unituxin (dinutuximab) is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy [see Clinical Studies (14) ] . Unituxin is …

Who makes Unituxin?
United Therapeutics Corporation is the labeler of record for Unituxin.

What form does Unituxin come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Unituxin prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has Unituxin been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.