Necitumumab
FDA Drug Information • Also known as: Portrazza
- Brand Names
- Portrazza
- Drug Class
- Epidermal Growth Factor Receptor Antagonist [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: CARDIOPULMONARY ARREST and HYPOMAGNESEMIA Cardiopulmonary arrest and/or sudden death occurred in 3.0% 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 [see Warnings and Precautions ( 5.1 , 5.2 )] . Hypomagnesemia occurred in 83% of patients receiving PORTRAZZA in combination with gemcitabine and cisplatin, and was severe in 20% of patients. 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 [see Warnings and Precautions ( 5.2 )] . 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 )
Description
11 DESCRIPTION Necitumumab is an anti-EGFR recombinant human monoclonal antibody of the IgG1 kappa isotype that specifically binds to the ligand binding site of the human EGFR. Necitumumab has an approximate molecular weight of 144.8 kDa. Necitumumab is produced in genetically engineered mammalian NS0 cells. PORTRAZZA is a sterile, preservative free, clear to slightly opalescent and colorless to slightly yellow solution. PORTRAZZA is available in single-dose vials for intravenous infusion following dilution. Each vial contains 800 mg PORTRAZZA in 50 mL (16 mg/mL). Each mL contains necitumumab (16 mg), citric acid anhydrous (0.256 mg), glycine (9.984 mg), mannitol (9.109 mg), polysorbate 80 (0.1 mg), sodium chloride (2.338 mg), sodium citrate dihydrate (2.55 mg), and water for injection, pH 6.0.
What Is Necitumumab Used For?
1 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 ) 1.1 Squamous Non-Small Cell Lung Cancer (NSCLC) PORTRAZZA™ is indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. 1.2 Limitation of Use 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 )] .
Dosage and Administration
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 ) 2.1 Recommended Dose and Schedule The recommended dose of PORTRAZZA is 800 mg administered as an intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion. Continue PORTRAZZA until disease progression or unacceptable toxicity. 2.2 Premedication For patients who have experienced a previous Grade 1 or 2 infusion-related reaction (IRR), pre-medicate with diphenhydramine hydrochloride (or equivalent) prior to all subsequent PORTRAZZA infusions [see Dosage and Administration ( 2.3 )] . For patients who have experienced a second Grade 1 or 2 occurrence of IRR, pre-medicate for all subsequent infusions, with diphenhydramine hydrochloride (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to each PORTRAZZA infusion [see Dosage and Administration ( 2.3 )] . 2.3 Dose Modifications Infusion-Related Reactions (IRR) Reduce the infusion rate of PORTRAZZA by 50% for Grade 1 IRR [see Dosage and Administration ( 2.2 ) and Warnings and Precautions ( 5.5 )] . Stop the infusion for Grade 2 IRR until signs and symptoms have resolved to Grade 0 or 1; resume PORTRAZZA at 50% reduced rate for all subsequent infusions [see Dosage and Administration ( 2.2 ) and Warnings and Precautions ( 5.5 )] . Permanently discontinue PORTRAZZA for Grade 3 or 4 IRR [see Dosage and Administration ( 2.2 ) and Warnings and Precautions ( 5.5 )] . Dermatologic Toxicity Withhold PORTRAZZA for Grade 3 rash or acneiform rash until symptoms resolve to Grade ≤2, then resume PORTRAZZA at reduced dose of 400 mg for at least 1 treatment cycle. If symptoms do not worsen, may increase dose to 600 mg and 800 mg in subsequent cycles. Permanently discontinue PORTRAZZA if: - Grade 3 rash or acneiform rash do not resolve to Grade ≤2 within 6 weeks, - Reactions worsen or become intolerable at a dose of 400 mg - Patient experiences Grade 3 skin induration/fibrosis [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 )] or - Grade 4 dermatologic toxicity [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 )] . 2.4 Preparation for Administration Inspect vial contents for particulate matter and discoloration prior to dilution [see Description ( 11 )] . Discard the vial if particulate matter or discoloration is identified. 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 [see How Supplied/Storage and Handling ( 16.2 )] . Dilute the required volume of PORTRAZZA with 0.9% Sodium Chloride Injection, USP in an intravenous infusion container to a final volume of 250 mL. Do not use solutions containing dextrose. Gently invert the container to ensure adequate mixing. DO NOT FREEZE OR SHAKE the infusion solution. DO NOT dilute with other...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse drug reactions are discussed in greater detail in other sections of the label: Cardiopulmonary Arrest [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Hypomagnesemia [see Boxed Warning and Warnings and Precautions ( 5.2 )] . Venous and Arterial Thromboembolic Events [see Warnings and Precautions ( 5.3 )] . Dermatologic Toxicities [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.4 )] . Infusion-Related Reactions [see Dosage and Administration ( 2.2 , 2.3 ) and Warnings and Precautions ( 5.5 )] . Non-Squamous NSCLC - Increased Toxicity and Increased Mortality [see Warnings and Precautions ( 5.6 ) and Clinical Studies ( 14.2 )] . 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PORTRAZZA was evaluated in two randomized, open-label trials comparing PORTRAZZA plus gemcitabine and cisplatin to gemcitabine and cisplatin alone in patients with squamous NSCLC (Study 1), and PORTRAZZA plus pemetrexed and cisplatin to pemetrexed and cisplatin alone in patients with non-squamous NSCLC (Study 2). Since the data in Study 2 demonstrated similar incidence of adverse reactions over control as observed in Study 1, the safety data from Study 1 alone is described below. For patients who received at least 1 dose of treatment in Study 1, the median age was 62 years (range 32 to 84), 83% were male; 84% were Caucasian; and 92% were smokers. Baseline ECOG performance status was 0 or 1 for 91%, and 2 for 9% of patients; 90% had metastatic disease in 2 or more sites. Patients received PORTRAZZA 800 mg intravenously on days 1 and 8 of each 21 day cycle in combination with up to six cycles of gemcitabine (1250 mg/m 2 on days 1 and 8) and cisplatin (75 mg/m 2 on day 1). Patients received PORTRAZZA until progressive disease or unacceptable toxicity. Patients in the gemcitabine and cisplatin alone arm received a maximum of 6 cycles, while patients in the PORTRAZZA plus gemcitabine and cisplatin arm demonstrating at least stable disease were permitted to continue to receive additional cycles of PORTRAZZA until disease progression or unacceptable toxicity. The median duration of exposure to PORTRAZZA in 538 patients who received at least 1 dose of treatment in Study 1 was 4.6 months (range 0.5 months to 34 months), including 182 patients exposed for at least 6 months and 41 patients exposed for greater than 1 year. Patients were monitored for safety until 30 days after treatment discontinuation and resolution of treatment-emergent adverse events. The most common adverse reactions (all grades) observed in PORTRAZZA-treated patients at a rate of ≥15% and ≥2% higher than gemcitabine and cisplatin alone were rash (44%), vomiting (29%), diarrhea (16%), and dermatitis acneiform (15%). The most common severe (Grade 3 or higher) adverse events that occurred at a ≥2% higher rate in PORTRAZZA-treated patients compared to patients treated with gemcitabine and cisplatin alone were venous thromboembolic events (5%; including pulmonary embolism), rash (4%), and vomiting (3%). Table 1 contains selected adverse drug reactions observed in Study 1 at an incidence of ≥5% in the PORTRAZZA arm and at ≥2% higher incidence than the control arm. Table 1: Adverse Reactions Occurring at Incidence Rate ≥5% All Grades or a ≥2% Grade 3-4 Difference Between Arms in Patients Receiving PORTRAZZA in Study 1 a...
Contraindications
4 CONTRAINDICATIONS None None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy 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...
Overdosage
10 OVERDOSAGE There has been limited experience with PORTRAZZA overdose in human clinical trials. The highest dose of PORTRAZZA studied clinically in a human dose-escalation Phase 1 study was 1000 mg once a week and once every other week. Two out of 9 patients in the every other week cohort experienced dose-limiting toxicities (e.g., a combination of Grade 3 headache, vomiting, and nausea). There is no known antidote for PORTRAZZA overdose.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied PORTRAZZA is supplied in single-dose vials as a sterile, preservative-free solution: 800 mg/50 mL (16 mg/mL) NDC 0002-7716-01 16.2 Storage and Handling 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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.