Dosage & 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.
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Portrazza Prescribing Information
- 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 ].
- 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 ].
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.
Limitation of Use
PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung cancer [see Warnings and Precautions and Clinical Studies ].
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.
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 ].
- 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 ].
Dose Modifications
Infusion-Related Reactions (IRR)
- Reduce the infusion rate of PORTRAZZA by 50% for Grade 1 IRR [see Dosage and Administration and Warnings and Precautions ].
- 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 and Warnings and Precautions ].
- Permanently discontinue PORTRAZZA for Grade 3 or 4 IRR [see Dosage and Administration and Warnings and Precautions ].
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:
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- Grade 3 rash or acneiform rash do not resolve to Grade ≤2 within 6 weeks,
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- Reactions worsen or become intolerable at a dose of 400 mg
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- Patient experiences Grade 3 skin induration/fibrosis [see Warnings and Precautions and Adverse Reactions ] or
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- Grade 4 dermatologic toxicity [see Warnings and Precautions and Adverse Reactions ].
Preparation for Administration
Inspect vial contents for particulate matter and discoloration prior to dilution [see Description ]. 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 ].
- 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 solutions or co-infuse with other electrolytes or medication.
- Store diluted infusion solution for no more than 24 hours at 2° to 8°C (36° to 46°F), or no more than 4 hours at room temperature (up to 25°C [77°F]).
- Discard vial with any unused portion of PORTRAZZA.
Administration
Visually inspect the diluted solution for particulate matter and discoloration prior to administration. If particulate matter or discoloration is identified, discard the solution.
Administer diluted PORTRAZZA infusion via infusion pump over 60 minutes through a separate infusion line. Flush the line with 0.9% Sodium Chloride Injection, USP at the end of the infusion.
Injection: 800 mg/50 mL (16 mg/mL) solution in a single-dose vial
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 ]. 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.
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.
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 [see Use in Specific Populations ]. Advise females of reproductive potential to use effective contraception during treatment with PORTRAZZA and for three months following the final dose.
Pediatric Use
The safety and effectiveness of PORTRAZZA have not been established in pediatric patients.
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[see Adverse Reactions ], 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.
Renal Impairment
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 ].
Hepatic Impairment
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 ].
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