Unituxin

WARNING: SERIOUS INFUSION REACTIONS AND NEUROTOXICITY

• Infusion Reactions: Life-threatening infusion adverse reactions occur with Unituxin. Administer required prehydration and premedication. Immediately interrupt for severe infusion reactions and permanently discontinue for anaphylaxis
  [see

  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

  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/m2/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/m2/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.
  HypotensionSymptomatic 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/m2/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.

  and

  5.1 Serious Infusion Reactions

  Serious infusion reactions requiring urgent intervention, including blood pressure support, bronchodilator therapy, corticosteroids, infusion rate reduction, infusion interruption, or permanent discontinuation of Unituxin, included facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, and hypotension. Infusion reactions generally occurred during or within 24 hours of completing the Unituxin infusion. Due to overlapping signs and symptoms, it was not possible to distinguish between infusion reactions and hypersensitivity reactions in some cases.

  In Study 1, Severe (Grade 3 or 4) infusion reactions occurred in 35 (26%) patients in the Unituxin/13-cis-retinoic acid (RA) group compared to 1 (1%) patient receiving RA alone. Severe urticaria occurred in 17 (13%) patients in the Unituxin/RA group but did not occur in the RA group. Serious adverse reactions consistent with anaphylaxis and resulting in permanent discontinuation of Unituxin occurred in 2 (1%) patients in the Unituxin/RA group. Additionally, 1 (0.1%) patient had multiple cardiac arrests and died within 24 hours after having received Unituxin in Study 2.

  Prior to each Unituxin dose, administer required intravenous hydration and premedication with antihistamines, analgesics, and antipyretics

  [see Dosage and Administration (2.2)]

  . Monitor patients closely for signs and symptoms of infusion reactions during and for at least 4 hours following completion of each Unituxin infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.

  For mild to moderate infusion reactions, such as transient rash, fever, rigors, and localized urticaria, that respond promptly to antihistamines or antipyretics, decrease the Unituxin infusion rate and monitor closely. Immediately interrupt or permanently discontinue Unituxin and institute supportive management for severe or prolonged infusion reactions. Permanently discontinue Unituxin and institute supportive management for life-threatening infusion reactions

  [see Dosage and Administration (2.3)]

  .

  ]
  .
• Neurotoxicity: Unituxin causes severe neuropathic pain. Administer intravenous opioid prior to, during, and for 2 hours following completion of the Unituxin infusion. Severe peripheral sensory neuropathy ranged from 2% to 9% in patients with neuroblastoma. Severe peripheral motor neuropathy has also been reported. Discontinue for severe unresponsive pain, severe sensory neuropathy, and moderate to severe peripheral motor neuropathy
  [see

  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

  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/m2/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/m2/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.
  HypotensionSymptomatic 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/m2/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.

  and

  5.2 Neurotoxicity

  Pain

  In Study 1, 114 (85%) patients treated in the Unituxin/RA group experienced pain despite pre-treatment with analgesics, including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the Unituxin/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the Unituxin infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia.

  Premedicate with analgesics, including intravenous opioids, prior to each dose of Unituxin and continue analgesics until 2 hours following completion of Unituxin

  [see Dosage and Administration (2.2)]

  .

  For severe pain, decrease the Unituxin infusion rate to 0.875 mg/m²/hour. Discontinue Unituxin if pain is not adequately controlled despite infusion rate reduction and institution of maximum supportive measures

  [see Dosage and Administration (2.3)]

  .

  Peripheral Neuropathy

  In Study 1, severe (Grade 3) peripheral sensory neuropathy occurred in 2 (1%) patients and severe peripheral motor neuropathy occurred in 2 (1%) patients in the Unituxin/RA group. No patients treated with RA alone experienced severe peripheral neuropathy. The duration and reversibility of peripheral neuropathy occurring in Study 1 was not documented. In Study 3, no patients experienced peripheral motor neuropathy. Among the 9 (9%) patients who experienced peripheral sensory neuropathy of any severity, the median (min, max) duration of peripheral sensory neuropathy was 9 (3, 163) days.

  In a study of a related anti-GD2 antibody conducted in 12 adult patients with metastatic melanoma, 2 (13%) patients developed severe motor neuropathy. One patient developed lower extremity weakness and inability to ambulate that persisted for approximately 6 weeks. Another patient developed severe lower extremity weakness resulting in an inability to ambulate without assistance that lasted for approximately 16 weeks and neurogenic bladder that lasted for approximately 3 weeks. Complete resolution of motor neuropathy was not documented in this case.

  Permanently discontinue Unituxin in patients with peripheral motor neuropathy of Grade 2 or greater severity, Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, or Grade 4 sensory neuropathy

  [see Dosage and Administration (2.3)]

  .

  Neurological Disorders of the Eye

  Neurological disorders of the eye experienced by 2 or more patients treated with Unituxin in Studies 1, 2, or 3 included blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and papilledema.

  In Study 1, 3 (2%) patients in the Unituxin/RA group experienced blurred vision, compared to no patients in the RA group. Diplopia, mydriasis, and unequal pupillary size occurred in 1 patient each in the Unituxin/RA group, compared to no patients in the RA group. The duration of eye disorders occurring in Study 1 was not documented. In Study 3, eye disorders occurred in 16 (15%) patients, and in 3 (3%) patients resolution of the eye disorder was not documented. Among the cases with documented resolution, the median duration of eye disorders was 4 days (range: 0, 221 days).

  Interrupt Unituxin 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 Unituxin is warranted, decrease the Unituxin dose by 50%. Permanently discontinue Unituxin in patients with recurrent signs or symptoms of an eye disorder following dose reduction and in patients who experience loss of vision

  [see Dosage and Administration (2.3)]

  .

  Prolonged Urinary Retention

  Urinary retention that persists for weeks to months following discontinuation of opioids has occurred in patients treated with Unituxin. Permanently discontinue Unituxin in patients with urinary retention that does not resolve following discontinuation of opioids

  [see Dosage and Administration (2.3)and Postmarketing Experience (6.3)]

  .

  Transverse Myelitis

  Transverse myelitis has occurred in patients treated with Unituxin. Promptly evaluate any patient with signs or symptoms of transverse myelitis, such as weakness, paresthesia, sensory loss, or incontinence. Permanently discontinue Unituxin in patients who develop transverse myelitis

  [see Dosage and Administration (2.3)and Postmarketing Experience (6.3)].

  Reversible Posterior Leukoencephalopathy Syndrome

  Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has occurred in patients treated with Unituxin. Institute appropriate medical treatment and permanently discontinue Unituxin in patients with signs and symptoms of RPLS (eg, severe headache, hypertension, visual changes, lethargy, or seizures)

  [see Dosage and Administration (2.3)and Postmarketing Experience (6.3)]

  .

  ]
  .

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

• Verify that patients have adequate hematologic, respiratory, hepatic, and renal function prior to initiating each course of Unituxin
  [see

  14 CLINICAL STUDIES

  The safety and effectiveness of Unituxin was evaluated in a randomized, open-label, multicenter trial conducted in pediatric patients with high-risk neuroblastoma (Study 1). All patients had received prior 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 were randomized between Day 50 and Day 77 post-autologous stem cell transplantation.

  Patients were required to have achieved at least a partial response prior to autologous stem cell transplantation, have no evidence of disease progression following completion of front-line multi-modality therapy, have adequate pulmonary function (no dyspnea at rest and peripheral arterial oxygen saturation of at least 94% on room air), adequate hepatic function (total bilirubin <1.5× the upper limit of normal and ALT <5× the upper limit of normal), adequate cardiac function (shortening fraction of >30% by echocardiogram, or if shortening fraction abnormal, ejection fraction of 55% by gated radionuclide study), and adequate renal function (glomerular filtration rate at least 70 mL/min/1.73 m²). Patients with systemic infections or a requirement for concomitant systemic corticosteroids or immunosuppressant usage were not eligible for enrollment.

  Patients randomized to the Unituxin/RA arm received up to 5 cycles of Unituxin (clinical trials material) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) (Table 8) or interleukin-2 (IL-2) (Table 9) plus 13-cis-retinoic acid (RA), followed by 1 cycle of RA alone. Patients randomized to the RA arm received 6 cycles of RA. Unituxin was administered at a dose of 17.5 mg/m²/day (equivalent to 25 mg/m²/day of clinical trials material) on 4 consecutive days. Patients in both treatment arms received 6 cycles of RA at a dose of 160 mg/m²/day orally (for patients weighing more than 12 kg) or 5.33 mg/kg/day (for patients weighing less than or equal to 12 kg) in 2 divided doses for 14 consecutive days.

  Table 8: Dosage Regimen in the Unituxin/RA Arm for Cycles 1, 3, and 5

  Cycle Day	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15-24
  GM-CSFGM-CSF: 250 µg/m2/day, administered by either subcutaneous injection (recommended) or IV infusion administered over 2 hours.	X	X	X	X	X	X	X	X	X	X	X	X	X	X
  UnituxinUnituxin: 17.5 mg/m2/day, administered by diluted IV infusion over 10 to 20 hours.				X	X	X	X
  RARA: for >12 kg body weight, 80 mg/m2orally twice daily for a total dose of 160 mg/m2/day; for ≤12 kg body weight, 2.67 mg/kg orally twice daily for a total daily dose of 5.33 mg/kg/day (round dose up to nearest 10 mg).											X	X	X	X	X

  Table 9: Dosage Regimen in the Unituxin/RA Arm for Cycles 2 and 4

  Cycle Day	1	2	3	4	5	6	7	8	9	10	11	12-14	15-28	29-32
  IL-2IL-2: 3 MIU/m2/day administered by continuous IV infusion over 96 hours on Days 1 to 4 and 4.5 MIU/m2/day on Days 8 to 11.	X	X	X	X				X	X	X	X
  UnituxinUnituxin: 17.5 mg/m2/day, administered by diluted IV infusion over 10 to 20 hours.								X	X	X	X
  RARA: for >12 kg body weight, 80 mg/m2orally twice daily for a total dose of 160 mg/m2/day; for ≤12 kg body weight, 2.67 mg/kg orally twice daily for a total daily dose of 5.33 mg/kg/day (round dose up to nearest 10 mg).													X

  A total of 226 patients were randomized, 113 patients to each arm. In general, demographic and baseline tumor characteristics were similar across study arms. Across the study population, 60% were male, the median age was 3.8 years and 3% of patients were less than 1.5 years, 82% were White and 7% were Black. The majority (80%) of patients had International Neuroblastoma Staging System Stage 4 disease. Thirty-five percent of patients had a complete response, 43% had a very good partial response, and 23% had a partial response to therapy received prior to autologous stem cell transplant. Forty-six percent of patients had neuroblastoma that was not MYCN-amplified, 36% had tumors with known MYCN-amplification, and MYCN status was unknown or missing in 19% of patients. Forty-three percent of patients had hyperdiploid tumors, 36% had diploid tumors, and DNA ploidy status was unknown or missing in 21% of patients.

  The major efficacy outcome measure was investigator-assessed event-free survival (EFS), defined as the time from randomization to the first occurrence of relapse, progressive disease, secondary malignancy, or death. Overall survival (OS) was also evaluated. After observing a numerical improvement in EFS based on the seventh interim analysis, the Data Monitoring Committee recommended termination of accrual. Efficacy results are shown in Table 10.

  Table 10: Efficacy Results

  Efficacy Parameter		Unituxin/RA arm n=113	RA arm n=113
  NR, not reached
  EFS	No. of Events (%)	33 (29%)	50 (44%)
  	Median (95% CI) (years)	NR (3.4, NR)	1.9 (1.3, NR)
  	Hazard Ratio (95% CI)	0.57 (0.37, 0.89)
  	p-value (log-rank test)Compared to the allocated alpha of 0.01 pre-specified for the seventh interim analysis of EFS	0.01
  OSBased on an additional 3 years of follow up after the seventh interim analysis of EFS	No. of Events (%)	31 (27%)	48 (42%)
  	Median (95% CI) (years)	NR (7.5, NR)	NR (3.9, NR)
  	Hazard Ratio (95% CI)	0.58 (0.37, 0.91)

  The Kaplan-Meier curve of EFS is shown in Figure 1.

  Figure 1: Kaplan-Meier Curve of Event-Free Survival

  

  Figure 1

  ].
• Administer required premedication and hydration prior to initiation of each Unituxin infusion
  [see

  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.

  ]
  .

Injection: 17.5 mg/5 mL (3.5 mg/mL) as a clear and colorless to slightly opalescent solution in a single-dose vial.

Based on its mechanism of action, Unituxin may cause fetal harm when administered to a pregnant woman