PORTRAZZA

Antineoplastic Monoclonal Antibodies Targeting EGFR

Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Necitumumab is a clear to slightly opalescent, colorless to pale-yellow solution. Discard the vial if the solution is cloudy, discolored, or contains extraneous particulate matter.
 
Infusion-Related Reactions:
First grade 1 or 2 infusion-related reaction: Premedicate all subsequent infusions with diphenhydramine (or equivalent).
Second grade 1 or 2 infusion-related reaction: Premedicate all subsequent infusions with diphenhydramine (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent).

Preparation:
Withdraw the required volume of drug and dilute with 0.9% Sodium Chloride injection in an IV infusion container to a final volume of 250 mL. Do not use solutions containing dextrose.
Mix the diluted solution by gentle inversion. Do not shake.
Do not dilute with other solutions or co-infuse with other electrolytes or medications.
Discard partially used or empty vials of necitumumab.
Storage: After preparation, store diluted solution either at room temperature (up to 25 degrees C or 77 degrees F) for no more than 4 hours, or under refrigeration (2 to 8 degrees C or 36 to 46 degrees F) for no more than 24 hours.
 
Administration:
Administer via infusion pump over 60 minutes through a separate infusion line.
Flush the line with 0.9% Sodium Chloride injection at the end of the infusion.

hypomagnesemia / Delayed / 20.0-20.0
hypophosphatemia / Delayed / 8.0-8.0
hypocalcemia / Delayed / 4.0-6.0
hypokalemia / Delayed / 5.0-5.0
thromboembolism / Delayed / 4.0-5.0
pulmonary embolism / Delayed / 4.0-4.0
rash / Early / 4.0-4.0
cardiac arrest / Early / 3.0-3.0
vomiting / Early / 3.0-3.0
stroke / Early / 2.0-2.0
diarrhea / Early / 2.0-2.0
myocardial infarction / Delayed / 1.0-1.0
acneiform rash / Delayed / 1.0-1.0
stomatitis / Delayed / 1.0-1.0
hemoptysis / Delayed / 1.0-1.0
weight loss / Delayed / 0.7-0.7
acne vulgaris / Delayed / 0.4-0.4
conjunctivitis / Delayed / 0.4-0.4
pruritus / Rapid / 0.2-0.2
thrombosis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
ocular hemorrhage / Delayed / Incidence not known

antibody formation / Delayed / 1.4-4.1
dysphagia / Delayed / 3.0-3.0
erythema / Early / Incidence not known
ocular infection / Delayed / Incidence not known
blepharitis / Early / Incidence not known
conjunctival hyperemia / Early / Incidence not known
blurred vision / Early / Incidence not known

headache / Early / 11.0-11.0
xerosis / Delayed / 7.0-7.0
maculopapular rash / Early / Incidence not known
ocular irritation / Rapid / Incidence not known
ocular pruritus / Rapid / Incidence not known
xerophthalmia / Early / Incidence not known
lacrimation / Early / Incidence not known
ocular pain / Early / Incidence not known

Cardiac arrest, cardiopulmonary arrest, and/or sudden death have occurred in patients treated with necitumumab in combination with gemcitabine and cisplatin. Closely monitor serum electrolytes prior to each dose of necitumumab and for 8 weeks after the last dose; aggressively correct any electrolyte imbalance that is detected such as hypomagnesemia, hypokalemia, and hypocalcemia. Do not administer necitumumab if grade 3 or 4 electrolyte abnormalities are present until they have resolved to grade 2 or less. In a randomized, open-label clinical trial, 12 of the 15 necitumumab-treated patients (n = 538) who experienced cardiopulmonary arrest or sudden death had comorbid conditions such as a history of coronary artery disease (CAD), hypomagnesemia, chronic obstructive pulmonary disease (COPD), and hypertension. Patients with significant CAD, myocardial infarction within 6 months, uncontrolled hypertension, and uncontrolled congestive heart failure (CHF) were excluded from this trial. Use necitumumab with caution in patients with a history of CAD, CHF, or cardiac arrhythmias, as the risk of cardiac arrest or sudden death is not known.

PORTRAZZA

Rx

Recombinant human lgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands
Indicated for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC), in combination with gemcitabine and cisplatin
Black box warning for cardiopulmonary arrest and hypomagnesemia; monitor serum electrolytes, including serum magnesium, potassium, and calcium prior to each infusion

800 mg IV over 60 minutes on days 1 and 8, followed by gemcitabine (1,250 mg/m2 IV on days 1 and 8) and cisplatin (75 mg/m2 IV on day 1), every 3 weeks for 6 cycles. After completion of 6 cycles of chemotherapy, continue necitumumab 800 mg IV over 60 minutes on days 1 and 8, every 3 weeks until disease progression or unacceptable toxicity.[60339] Administer appropriate hydration prior to cisplatin administration and maintain hydration and adequate urinary output for 24 hours after cisplatin administration. Treatment with necitumumab, gemcitabine, and cisplatin significantly improved median overall survival (OS) in patients with previously untreated metastatic squamous NSCLC compared with gemcitabine and cisplatin without necitumumab (11.5 months vs. 9.9 months) in a randomized, open-label trial. Investigator-assessed progression-free survival (PFS) was also significantly improved in the necitumumab arm (5.7 months vs. 5.5 months); the overall response rate was 31% versus 29%, respectively. Necitumumab is not effective in the treatment of non-squamous NSCLC. Another multicenter, randomized, open-label clinical trial was closed early due to an increased incidence of death due to any cause and thromboembolic events in patients who received necitumumab plus pemetrexed and cisplatin compared to pemetrexed and cisplatin alone; more serious (51% vs. 41%) and fatal (16% vs. 10%) toxicities occurred in the necitumumab arm, as well as an increased incidence of cardiopulmonary arrest/sudden death within 30 days of the last study drug (3.3% vs. 1.3%). In this study, neither OS, PFS, nor ORR were significantly improved with the addition of necitumumab to pemetrexed and cisplatin.[60339]

Formal studies have not evaluated the effect of hepatic impairment on necitumumab exposure, therefore specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Patients with severe hepatic impairment were not enrolled in clinical trials.

Formal studies have not evaluated the effect of renal impairment on necitumumab exposure, therefore specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

PORTRAZZA Intravenous Inj Sol: 1mL, 16mg

800 mg IV on day 1 and 8.

800 mg IV on day 1 and 8.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Necitumumab is an anti-EGFR recombinant human monoclonal antibody of the IgG1 kappa isotope that specifically binds to and blocks the ligand binding site of the human EGFR. Expression and activation of EGFR has been correlated with malignant progression, angiogenesis, and inhibition of apoptosis. In vitro, necitumumab induces EGFR internalization and degradation, leading to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells. Compared with gemcitabine and cisplatin alone, the addition of necitumumab increased antitumor activity in vivo in studies using xenograft models of human cancer, including non-small cell lung cancer (NSCLC), in implanted mice.

Necitumumab is administered intravenously, and exhibits dose-dependent pharmacokinetics. After administration of necitumumab 800 mg on days 1 and 8 of each 21 day cycle, the estimated mean total systemic clearance at steady-state is 14.1 mL/h (CV, 39%), the steady-state volume of distribution (Vd) is 7 L (CV, 31%), and the elimination half-life is approximately 14 days. The predicted time to reach steady state is approximately 100 days.

Although there are no adequate and well-controlled studies in pregnant women, necitumumab can cause fetal harm when administered during pregnancy based on its mechanism of action and animal data. Disruption or depletion of EGFR in animal models causes impairment of embryofetal development, including adverse effects on placental, lung, cardiac, skin, and neural development. In mice, EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/post-natal survival and development; EGFR inhibition can prevent implantation, cause embryo-fetal loss during various stages of gestation, and can cause developmental anomalies and early death in surviving fetuses. Human IgG1 is known to cross the placenta; therefore, necitumumab has the potential to cross the placenta and be transmitted from mother to fetus. In monkeys, administration of a chimeric anti-EGFR antibody that binds to an epitope overlapping that of necitumumab during organogenesis resulted in detectable exposure in the amniotic fluid and in the serum of embryos from treated dams. While no fetal malformations or other clear teratogenic effects occurred, there was an increased incidence of embryo-lethality and abortions.

It is not known whether necitumumab is present in human milk. Many drugs are excreted in human milk including antibodies. Due to the potential for serious adverse reactions in nursing infants from necitumumab, advise women to discontinue breast-feeding during treatment and for 3 months after the last dose.