UNITUXIN*
Manufacturer DetailsUNITED THERAPEUTICS CORPORATION INC.
UNITED THERAPEUTICS CORPORATION INC.
Compositions:
Dinutuximab- mg,
Dinutuximab- mg,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit |
List of Related Indications:
- For the treatment of Pediatric Patients with High-Risk Neuroblastoma who Acheive at least a Partial Response to Prior First-Line Multiagent Multimodality Therapy
List Of Drugs:
- Dinutuximab-Unituxin- @-(Mar 2015)- Anti-Cancer
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No drug-drug interaction studies have been conducted with dinutuximab.
Indication:
UNITUXIN (dinutuximab) injection, for intravenous use
Initial U.S. Approval: 2015
WARNING: SERIOUS INFUSION REACTIONS AND NEUROPATHY
See full prescribing information for complete boxed warning.
Infusion Reactions: Life-threatening infusion adverse reactions occur
with Unituxin. Administer requiredprehydration and premedication.
Immediately interrupt for severe infusion reactions and permanently
discontinue for anaphylaxis
Neuropathy: 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 motor neuropathy was observed in adults.
Discontinue for severe unresponsive pain, severe sensory neuropathy,
or moderate to severe peripheral motor neuropathy
.
Proprietary Name- UNITUXIN*
Established Name- Dinutuximab
Applicant- United Therapeutic Corporation
Indication- For the treatment of Pediatric Patients with high risk
Neuroblastoma who acheive at least a Partial response
to Prior First line Multiagent Multimodality Therapy
Approval Date- 3/10/2015
Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 2015)
SUBSEQUENT APPROVAL-
Indication- In Combination with Granulocyte-Macrophage Colony
Stimulating Factor(GM-CSF) , Interleukin -2 (IL-) and
13-Cis-retonic acid (RA), for the treatment of Pediatric
Patients with High-Risk Neuroblastoma who acheive
at least a partial response to prior first-line, Multimodality
therapy
March 10,2015
Approved by U.S.FDA as on 30-06-2015 (Ref- FDA approved List- 2015)
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.9
Drug Name - Dinutuximab
Active Ingredient- Unituxin
Date of approval - 3/10/2015
FDA-approved use - To treat pediatric patients with high-risk
neuroblastoma
Approved by US FDA on 3/10/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
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.
Contra-Indications:
CONTRAINDICATIONS .
History of anaphylaxis to dinutuximab.
WARNINGS AND PRECAUTIONS.
Capillary leak syndrome and hypotension: Administer required
prehydration and monitor patients closely during treatment.
Depending upon severity, manage by interruption, infusion rate reduction,
or permanent discontinuation.
.
Infection: Interrupt until resolution of systemic infection.
.
Neurological Disorders of the Eye: Interrupt for dilated pupil with
sluggish light reflex or other visual disturbances and permanently
discontinue for recurrent eye disorders or loss of vision.
.
Bone marrow suppression: Monitor peripheral blood counts during
Unituxin therapy.
.
Electrolyte abnormalities: Monitor serum electrolytes closely.
.
Atypical hemolytic uremic syndrome: Permanently discontinue
Unituxin and institute supportive management.
.
Embryo-Fetal toxicity: May cause fetal harm. Advise females of
reproductive potential of potential risk to a fetus and to use
effective contraception.
Dosages/ Overdosage Etc:
Indication- For the treatment of Pediatric Patients with high risk
Neuroblastoma who acheive at least a Partial response
to Prior First line Multiagent Multimodality Therapy
SUBSEQUENT APPROVAL-
Indication- In Combination with Granulocyte-Macrophage Colony
Stimulating Factor(GM-CSF) , Interleukin -2 (IL-) and
13-Cis-retonic acid (RA), for the treatment of Pediatric
Patients with High-Risk Neuroblastoma who acheive
at least a partial response to prior first-line, Multimodality
therapy
INDICATIONS AND USAGE
Unituxin is a GD2-binding monoclonal antibody indicated, in combinatio
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.
DOSAGE AND ADMINISTRATION
17.5 mg/m2/day as a diluted intravenous infusion over 10 to 20 hours
for 4 consecutive days for up to 5 cycles.
DOSAGE FORMS AND STRENGTHS
Injection: 17.5 mg/5 mL (3.5 mg/mL) in a single-use vial.
Patient Information:
PATIENT COUNSELING INFORMATION
Serious Infusion Reactions Inform patients and caregivers of the risk
of serious infusion reactions and anaphylaxis and to immediately report
any signs or symptoms, such as facial or lip swelling, urticaria,
difficulty breathing, lightheadedness or dizziness that occur during
or within 24 hours following the infusion
Pain and Peripheral Neuropathy Inform patients and caregivers of the risk of
severe pain and peripheral sensory and motor neuropathy and to promptly
report severe or worsening pain and signs and symptoms of neuropathy
such as numbness, tingling, burning, or weakness
Capillary Leak Syndrome Inform patients and caregivers of the risk of capillary
leak syndrome and to immediately report any signs or symptoms
.
Hypotension Inform patients and caregivers of the risk of hypotension during
the infusion and to immediately report any signs or symptoms
Infection Inform patients and caregivers of the risk of infection following treatment
and to immediately report any signs or symptoms
Neurological Disorders of the Eye Inform patients and caregivers of the risk
of neurological disorders of the eye and to promptly report signs or symptoms
such as blurred vision, photophobia, ptosis, diplopia, or unequal pupil size
Bone Marrow Suppression Inform patients and caregivers of the risk of bone
marrow suppression, and to promptly report signs or symptoms of anemia,
thrombocytopenia, or infection
Electrolyte Abnormalities Inform patients and caregivers of the risk of electrolyte
abnormalities including hypokalemia, hyponatremia, and hypocalcemia,
and to report any signs or symptoms such as seizures, heart palpitations,
and muscle cramping
Atypical Hemolytic Uremic Syndrome Inform patients and caregivers of the
risk of hemolytic uremic syndrome and to report any signs or symptoms
such as fatigue, dizziness, fainting, pallor, edema, decreased urine output,
or hematuria
Embryo-Fetal Toxicity Advise women of reproductive potential of the
potential risk to the fetus if administered during pregnancy and the
need for use of effective contraception during and for at least two months
after completing therapy
.
Unituxin manufactured by:
United Therapeutics Corp.
Silver Spring, MD 20910
US License No. 1993
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Dinutuximab binds to the glycolipid GD2. This glycolipid is expressed on
neuroblastoma cells and on normal cells of neuroectodermal origin, including
the central nervous system and peripheral nerves. Dinutuximab binds to cell
surface GD2 and induces cell lysis of GD2expressing cells through
antibody-dependent cell-mediated cytotoxicity (ADCC) and
complement-dependent cytotoxicity (CDC).
2. Pharmacokinetics
The pharmacokinetics of dinutuximab was evaluated by a population
pharmacokinetic analysis in a clinical study of Unituxin in combination
with GM-CSF, IL-2, and RA.
In this study, 27 children with high-risk neuroblastoma (age: 3.9±1.9 years)
received up to 5 cycles of Unituxin at 17.5 mg/m2/day as an intravenous
infusion over 10 to 20 hours for 4 consecutive days every 28 days.
was 11.5 mcg/mL [20%, coefficient of variation (CV)].
The mean volume of distribution at steady state (Vd ss) was 5.4 L (28%).
The clearance was 0.21 L/day (62%) and increased with body size.
The terminal half-life was 10 days (56%).
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on its mechanism of action, Unituxin may cause fetal harm when administered
to a pregnant woman 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.
2 Lactation
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.
3. Pediatric Use
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)
.
4. Geriatric Use
The safety and effectiveness of Unituxin in geriatric patients have not been established.
