PORTRAZZA- necitumumab solution

Land: USA

Språk: engelska

Källa: NLM (National Library of Medicine)

Aktiva substanser:

necitumumab (UNII: 2BT4C47RUI) (necitumumab - UNII:2BT4C47RUI)

Tillgänglig från:

Eli Lilly and Company

INN (International namn):

necitumumab

Sammansättning:

necitumumab 16 mg in 1 mL

Administreringssätt:

INTRAVENOUS

Receptbelagda typ:

PRESCRIPTION DRUG

Terapeutiska indikationer:

PORTRAZZA™ is indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung cancer [see Warnings and Precautions (5.6) and Clinical Studies (14.2)] . None Risk Summary Based on animal data and its mechanism of action, PORTRAZZA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. Disruption or depletion of EGFR in animal models results in impairment of embryo-fetal development including effects on placental, lung, cardiac, skin, and neural development. The absence of EGFR signaling has resulted in embryolethality as well as post-natal death in animals (see Data) . No animal reproduction studies have been conducted with necitumumab. 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. Data Animal Data No animal studies have been conducted to evaluate the effect of necitumumab on reproduction and fetal development; however, based on its mechanism of action, PORTRAZZA can cause fetal harm or developmental anomalies. In mice, EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/postnatal survival and development. Reduction or elimination of embryo-fetal or maternal EGFR signaling can prevent implantation, can cause embryo-fetal loss during various stages of gestation (through effects on placental development) and can cause developmental anomalies and early death in surviving fetuses. Adverse developmental outcomes were observed in multiple organs in embryos/neonates of mice with disrupted EGFR signaling. Human IgG1 is known to cross the placenta; therefore, necitumumab has the potential to be transmitted from the mother to the developing fetus. In monkeys, administration of a chimeric anti-EGFR antibody that binds to an epitope overlapping that of necitumumab during the period of organogenesis resulted in detectable exposure of the antibody in the amniotic fluid and in the serum of embryos from treated dams. While no fetal malformations or other clear teratogenic effects occurred in offspring, there was an increased incidence of embryolethality and abortions. 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. Contraception Females Based on its mechanism of action, PORTRAZZA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with PORTRAZZA and for three months following the final dose. The safety and effectiveness of PORTRAZZA have not been established in pediatric patients. 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 [see Adverse Reactions (6.1)] , 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. No formal studies have been conducted to evaluate the effect of renal impairment on the exposure to necitumumab. Renal function has no influence on the exposure to necitumumab based on the population pharmacokinetic analysis of data from clinical trials [see Clinical Pharmacology (12.3)] . No formal studies have been conducted to evaluate the effect of hepatic impairment on the exposure to necitumumab. Mild or moderate hepatic impairment has no influence on the exposure to necitumumab based on the population pharmacokinetic analysis. No patients with severe hepatic impairment were enrolled in the clinical trials with PORTRAZZA [see Clinical Pharmacology (12.3)] .

Produktsammanfattning:

PORTRAZZA is supplied in single-dose vials as a sterile, preservative-free solution: Store vials in a refrigerator at 2° to 8°C (36° to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light. DO NOT FREEZE OR SHAKE the vial.

Bemyndigande status:

Biologic Licensing Application

Produktens egenskaper

PORTRAZZA - NECITUMUMAB SOLUTION
ELI LILLY AND COMPANY
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PORTRAZZA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR PORTRAZZA.
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)
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. (1.1)
Limitation of Use: PORTRAZZA is not indicated for treatment of
non-squamous non-small cell lung cancer.
(1.2, 5.6, 14.2)
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. (2.1)
DOSAGE FORMS AND STRENGTHS
Injection: 800 mg/50 mL (16 mg/mL) solution in a single-dose vial. (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Cardiopulmonary Arrest: Closely monitor serum electrolytes during and
after PORTRAZZA. (5.1)
Hypomagnesemia: Monitor prior to each infusion and for at least 8
weeks