UNITUXIN- dinutuximab injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DINUTUXIMAB (UNII: 7SQY4ZUD30) (DINUTUXIMAB - UNII:7SQY4ZUD30)

Available from:

United Therapeutics Corporation

INN (International Name):

DINUTUXIMAB

Composition:

DINUTUXIMAB 3.5 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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 contraindicated in patients with a history of anaphylaxis to dinutuximab. Risk Summary Based on its mechanism of action, Unituxin may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. Monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Risk Summary There is no information available on the presence of dinutuximab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. However, human IgG is present in human milk. Because of the potential for serious adverse reactions in a breastfed infant, advise a nursing woman to discontinue breastfeeding during treatment with Unituxin. Contraception Females Unituxin may cause fetal harm [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of Unituxin. The safety and effectiveness of Unituxin as part of multi-agent, multimodality therapy have been established in pediatric patients with high-risk neuroblastoma based on results of an open-label, randomized (1:1) trial conducted in 226 patients aged 11 months to 15 years (median age 3.8 years) (Study 1). Prior to enrollment, patients achieved at least a partial response to prior first-line therapy for high-risk neuroblastoma consisting of induction combination chemotherapy, maximum feasible surgical resection, myeloablative consolidation chemotherapy followed by autologous stem cell transplant, and received radiation therapy to residual soft tissue disease. Patients randomized to the Unituxin/13-cis-retinoic acid (RA) arm (Unituxin/RA) received up to 5 cycles of Unituxin in combination with alternating cycles of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) plus RA, followed by 1 cycle of RA alone. Patients randomized to the RA arm received up to 6 cycles of RA monotherapy. Study 1 demonstrated an improvement in event-free survival (EFS) and overall survival (OS) in patients in the Unituxin/RA arm compared to those in the RA arm [see Adverse Reactions (6), Clinical Pharmacology (12), and Clinical Studies (14)] . Juvenile Animal Toxicity Data Juvenile monkeys (13 to 18 months of age at study start) received dinutuximab daily via intravenous infusion for 4 consecutive days over five 28-day cycles at doses of 1, 3, or 10 mg/kg. Monkeys also received morphine during infusion for pain management. At the high dose of 10 mg/kg (approximately equal to the 17.5 mg/m2 clinical dose), mild degeneration of nerve fibers in the brain (medulla oblongata) and moderate degeneration of nerve fibers in the spinal cord (cervical, thoracic, and lumbar) were present. Mild neuronal and nerve fiber degeneration were also present in the dorsal root ganglia (cervical, thoracic, and lumbar). Nerve fiber degeneration in the spinal cord and neuronal degeneration in dorsal root ganglia persisted 6 months after the end of dosing, though at lower severity. At the 10 mg/kg dose level, nerve conduction velocity (NCV) analysis showed motor and sensory NCV decreases of less than 10% compared to vehicle controls, starting on Day 27 and continuing to Day 83. Sensory NCV decreases were still present at the end of the dosing period but were on a trend towards recovery 6 months after the end of dosing. The safety and effectiveness of Unituxin in geriatric patients have not been established. Unituxin has not been studied in patients with renal impairment. Unituxin has not been studied in patients with hepatic impairment.

Product summary:

Unituxin (dinutuximab) injection as a clear and colorless to slightly opalescent solution is supplied in a carton containing one 17.5 mg/5 mL (3.5 mg/mL) single-dose vial. NDC 66302-014-01 Store Unituxin vials under refrigeration at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light until time of use. Do not freeze or shake the vial.

Authorization status:

Biologic Licensing Application

Summary of Product characteristics

UNITUXIN- DINUTUXIMAB INJECTION
UNITED THERAPEUTICS CORPORATION
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
UNITUXIN SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR UNITUXIN.
UNITUXIN (DINUTUXIMAB) INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2015
WARNING: SERIOUS INFUSION REACTIONS AND NEUROTOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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 DOSAGE_
_AND ADMINISTRATION (2.2, 2.3) AND WARNINGS AND PRECAUTIONS (5.1)]_.
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 DOSAGE AND
ADMINISTRATION_
_(2.2, 2.3) AND WARNINGS AND PRECAUTIONS (5.2)]_.
INDICATIONS AND USAGE
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)
DOSAGE AND ADMINISTRATION
17.5 mg/m /day as a diluted intravenous infusion over 10 to 20 hours
for 4 consecutive days for up to 5
cycles. (2.1, 2.4)
DOSAGE FORMS AND STRENGTHS
Injection: 17.5 mg/5 mL (3.5 mg/mL) in a single-dose vial. (3)
CONTRAINDICATIONS
History of anaphylaxis to dinutuximab. (4)
WARNINGS AND PRECAUTIONS
Neurological Disorders of the Eye: Interrupt Unitux