Necitumumab- Portrazza -@- (Nov 2015)- Anti-cancer
Drug Name:Necitumumab- Portrazza -@- (Nov 2015)- Anti-cancer
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
PORTRAZZA (necitumumab) injection, for intravenous use
Initial U.S. Approval: 2015
WARNING: CARDIOPULMONARY ARREST and HYPOMAGNESEMIA
See full prescription information for complete boxed warning
Cardiopulmonary arrest and/or sudden death occurred in 3% of patients
treated with PORTRAZZA in combination with gemcitabine and cisplatin.
Closely monitor serum
electrolytes, including serum magnesium, potassium, and calcium,
with aggressive replacement when warranted during and after
PORTRAZZA administration. (5.1, 5.2)
Hypomagnesemia occurred in 83% of patients receiving PORTRAZZA
in combination with gemcitabine and cisplatin, and was severe in 20%.
Monitor patients for hypomagnesemia, hypocalcemia, and hypokalemia prior to
each dose of PORTRAZZA during treatment and for at least 8 weeks following
completion of PORTRAZZA.
Withhold PORTRAZZA for Grade 3 or 4 electrolyte abnormalities.
Replete electrolytes as medically appropriate. (5.2)
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.39
Drug Name - Necitumumab
Active Ingredient- Portrazza
Date of approval - 11/24/2015
FDA-approved use - To treat patients with advanced (metastatic)
squamous non-small cell lung cancer (NSCLC) who have previously
received medication specifically for treating their advanced lung
cancer
Approved by US FDA on 11/24/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
PORTRAZZA is an epidermal growth factor receptor (EGFR) antagonist indicated,
in combination with gemcitabine and cisplatin, for first-line treatment of patients
with metastatic squamous non-small cell lung cancer.
Limitation of Use:
PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung
cancer.
Adverse Reaction:
The most common adverse reactions (all grades) observed in
PORTRAZZA-treated patients at a rate of .30% and .2% higher than
gemcitabine and cisplatin alone arm were rash and hypomagnesemia.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
.
Cardiopulmonary Arrest: Closely monitor serum electrolytes during and
after PORTRAZZA.
Hypomagnesemia: Monitor prior to each infusion and for at least 8 weeks
following the completion of PORTRAZZA.
Withhold PORTRAZZA for Grade 3 or 4 electrolyte abnormalities; subsequent
cycles of PORTRAZZA may be administered in these patients once electrolyte
abnormalities have improved to Grade .2.
Replete electrolytes as necessary.
Venous and Arterial Thromboembolic Events (VTE and ATE):
Discontinue PORTRAZZA for severe VTE or ATE.
Dermatologic Toxicities: Monitor for dermatologic toxicities and withhold or
discontinue PORTRAZZA for severe toxicity. Limit sun exposure.
. Infusion-Related Reactions: Monitor for signs and symptoms during and
following infusion. Discontinue PORTRAZZA for severe reactions.
Increased Toxicity: Non-Squamous NSCLC - Increased toxicity and
increased mortality.
. Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of
reproductive potential of the potential risk to a fetus and to use
effective contraception.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
PORTRAZZA is an epidermal growth factor receptor (EGFR) antagonist indicated,
in combination with gemcitabine and cisplatin, for first-line treatment of patients
with metastatic squamous non-small cell lung cancer.
Limitation of Use:
PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung
cancer.
DOSAGE AND ADMINISTRATION
Recommended dose of PORTRAZZA is 800 mg (absolute dose) as an
intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week
cycle.
DOSAGE FORMS AND STRENGTHS
Injection: 800 mg/50 mL (16 mg/mL) solution in a single-dose vial.
Patient Information:
PATIENT COUNSELING INFORMATION
Hypomagnesemia Advise patients of risk of decreased blood levels of magnesium,
potassium and calcium.
Take medicines to replace the electrolytes exactly as advised by the physician.
Venous and Arterial Thromboembolic Events
Advise patients of increased risk of venous and arterial thromboembolic events
Skin reactions
Advise patients to minimize sun exposure with protective clothing
and use of sunscreen while receiving PORTRAZZA
Infusion-Related Reactions
Advise patients to report signs and symptoms of infusion reactions such as fever,
chills, or breathing problems
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus
Advise females of reproductive potential to use effective contraception during
treatment with PORTRAZZA and for three months following final dose
Lactation
Advise women not to breastfeed during treatment with PORTRAZZA and for three
months following the final dose
Literature issued November 2015
Manufactured by: Eli Lilly and Company, Indianapolis, IN 46285
US License No. 1891
Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Necitumumab is a recombinant human lgG1 monoclonal antibody that binds to the human
epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands.
Expression and activation of EGFR has been correlated with malignant progression,
induction of angiogenesis, and inhibition of apoptosis. Binding of necitumumab induces
EGFR internalization and degradation in vitro. In vitro, binding of necitumumab also
led to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells.
In in vivo studies using xenograft models of human cancer, including non-small cell lung
carcinoma, administration of necitumumab to implanted mice resulted in increased
antitumor activity in combination with gemcitabine and cisplatin as compared to mice
receiving gemcitabine and cisplatin alone.
2. Pharmacokinetics
Based on population pharmacokinetic (popPK) analysis of serum concentration data
from patients in clinical studies with PORTRAZZA, necitumumab exhibits dose-dependent
kinetics.
Following the administration of PORTRAZZA 800 mg on Days 1 and 8 of each 21 day
cycle, the estimated mean total systemic clearance (CLtot) at steady state is
14.1 mL/h (CV=39%), the steady state volume of distribution (Vss) is 7.0 L (CV=31%)
and the elimination half-life is approximately 14 days.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on animal data and its mechanism of action, PORTRAZZA can cause
fetal harm when administered to a pregnant woman
There are no available data for PORTRAZZA exposure in pregnant women.
Advise pregnant women of the potential risk to a fetus, and the risk to postnatal development.
In the U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
2 Lactation
Risk Summary
There is no information regarding the presence of necitumumab in human milk, the effects
on the breastfed infant, or the effects on milk production.
Because of the potential for serious adverse reactions in breastfed infants from
PORTRAZZA, advise a nursing woman not to breastfeed during treatment with
PORTRAZZA and for three months following the final dose.
3. Females and Males of Reproductive Potential
Contraception
Females
Based on its mechanism of action, PORTRAZZA can cause fetal harm when administered
to a pregnant woman Advise females of reproductive potential to use effective
contraception during treatment with PORTRAZZA and for three months following
the final dose.
4. Pediatric Use
The safety and effectiveness of PORTRAZZA have not been established in pediatric patients.
5. Geriatric Use
Of the 545 patients in the PORTRAZZA plus gemcitabine and cisplatin arm in Study 1,
213 (39%) were 65 years and over, while 108 (20%) were 70 years and over.
In an exploratory subgroup analysis of Study 1, the hazard ratio for overall survival
in patients 70 years or older was 1.03 (95% CI: 0.75, 1.42).
Of the adverse reactions listed in Table 1 , there was a higher incidence (.3%) of venous
thromboembolic events including pulmonary embolism in patients age 70 and over
compared to those who were younger than age 70.
