Version May 2024
Cardiopulmonary arrest and/or sudden death occurred in 3% of patients treated with necitumumab in combination with gemcitabine and cisplatin. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, with aggressive replacement when warranted during and after necitumumab administration.
Hypomagnesemia occurred in 83% of patients receiving necitumumab 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 necitumumab during treatment and for at least 8 weeks following completion of necitumumab. Withhold necitumumab for Grade 3 or 4 electrolyte abnormalities. Replete electrolytes as medically appropriate.
Note: For patients with a prior grade 1 or 2 infusion reaction, premedicate (prior to all subsequent necitumumab infusions) with diphenhydramine (or equivalent). For patients with a recurrent grade 1 or 2 infusion reaction, premedicate (prior to all subsequent necitumumab infusions) with diphenhydramine (or equivalent), acetaminophen, and dexamethasone (or equivalent).
Non–small cell lung cancer (squamous), metastatic: IV: 800 mg on days 1 and 8 of each 3-week treatment cycle (in combination with gemcitabine and cisplatin); continue until disease progression or unacceptable toxicity (Ref).
In the study, gemcitabine and cisplatin were administered for a maximum of 6 cycles, while patients without disease progression continued necitumumab as single-agent therapy (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.
Severe impairment: There is no dosage adjustment provided in the manufacturer’s labeling (has not been studied).
Dermatologic toxicity:
Grade 3 rash or acneiform rash: Withhold necitumumab treatment until symptoms resolve to grade 2 or lower, then resume necitumumab with the dose reduced to 400 mg for at least 1 treatment cycle. If symptoms do not worsen, may increase the dose to 600 mg and then 800 mg in subsequent cycles.
Grade 3 rash or acneiform rash that does not resolve to grade 2 or lower within 6 weeks: Permanently discontinue necitumumab.
Grade 3 rash or acneiform rash that worsens or is intolerable at the 400 mg dose: Permanently discontinue necitumumab.
Grade 3 skin induration/fibrosis: Permanently discontinue necitumumab.
Grade 4 dermatologic toxicity: Permanently discontinue necitumumab.
Electrolyte abnormality: Grade 3 or 4 electrolyte abnormality: Withhold necitumumab treatment; may resume when electrolyte abnormality has improved to grade 2 or lower (replete electrolytes as appropriate).
Infusion-related reactions:
Grade 1: Reduce necitumumab infusion rate by 50%.
Grade 2: Interrupt necitumumab infusion until signs/symptoms have resolved to grade 1 or 0, then resume with the rate reduced by 50% for all subsequent infusions.
Grade 3 or 4: Permanently discontinue necitumumab.
Thromboembolic events: Serious or life-threatening venous thromboembolism or arterial thromboembolism: Discontinue treatment necitumumab.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reaction percentages reported as part of a combination regimen with gemcitabine and cisplatin.
>10%:
Central nervous system: Headache (11%)
Dermatologic: Skin toxicity (79%; grades 3/4: 8%), skin rash (44%; grades 3/4: 4%), acneiform eruption (15%; grades 3/4: 1%)
Endocrine & metabolic: Hypomagnesemia (43% to 83%; grades 3/4: 20%), hypocalcemia (45%; grades 3/4: 6%; with albumin corrected: 36%; grades 3/4: 4%), hypophosphatemia (31%; grades 3/4: 8%), hypokalemia (28%; grades 3/4: 5%), weight loss (13%)
Gastrointestinal: Vomiting (29%), diarrhea (16%), stomatitis (11%)
1% to 10%:
Cardiovascular: Venous thromboembolism (9%; grades 3/4: 5%), arterial thromboembolism (5%; grades 3/4: 4%), pulmonary embolism (5%), cardiorespiratory arrest (3%), deep vein thrombosis (2%), cerebrovascular accident (≤2%), ischemia (≤2%), myocardial infarction (1%)
Dermatologic: Acne vulgaris (9%), paronychia (7%), pruritus (7%), xeroderma (7%), skin fissure (5%)
Immunologic: Antibody development (4%; neutralizing: 1%)
Ophthalmic: Conjunctivitis (7%)
Respiratory: Hemoptysis (10%)
Miscellaneous: Infusion related reaction (2%; grade 3: <1%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cardiopulmonary arrest: [US Boxed Warning]: Cardiopulmonary arrest and/or sudden death occurred in a small percentage of patients treated with necitumumab in combination with gemcitabine and cisplatin. Monitor serum electrolytes closely, including serum magnesium, potassium, and calcium, with aggressive replacement when warranted during and after necitumumab administration. Continue electrolyte monitoring for at least 8 weeks after the last dose. Some cardiopulmonary events were fatal; many of those patients had comorbid conditions (including a history of coronary artery disease, hypomagnesemia, chronic obstructive pulmonary disease, and/or hypertension). Patients with significant coronary artery disease, MI within 6 months, uncontrolled hypertension or uncontrolled heart failure were excluded from the squamous cell non-small cell lung cancer (NSCLC) study.
• Dermatologic toxicity: Dermatologic toxicity, including rash, dermatitis acneiform, acne, dry skin, pruritus, generalized rash, skin fissures, maculo-papular rash, and/or erythema occurs commonly; may be severe. Skin toxicity usually developed within the first 2 weeks of treatment and resolved within 17 weeks after onset. May require treatment interruption, dose reduction, or discontinuation. Patients should minimize exposure to the sun.
• Hypomagnesemia: [US Boxed Warning]: Hypomagnesemia occurred in a majority of patients receiving necitumumab in combination with gemcitabine and cisplatin; hypomagnesemia was severe in one-fifth of patients. Monitor for hypomagnesemia, hypocalcemia, and hypokalemia prior to each dose of necitumumab during treatment and for at least 8 weeks following completion of necitumumab. Withhold necitumumab for Grade 3 or 4 electrolyte abnormalities. Replete electrolytes as appropriate. May resume treatment when hypomagnesemia and related electrolyte abnormalities are improved to grade 2 or lower. The median time to development of hypomagnesemia was 6 weeks after treatment initiation.
• Infusion reactions: Infusion-related reactions have been reported with necitumumab, usually after the first or second infusion. Premedication was not routinely administered prior to the first dose in the squamous cell NSCLC study. Monitor for signs/symptoms of infusion reaction. Discontinue for serious or life-threatening reactions.
• Thromboembolism: Venous and arterial thromboembolic events (VTE and ATE) were observed with necitumumab, including grades 3 and 4 events and some fatalities. The most common VTEs were deep vein thrombosis and pulmonary embolism and the most common ATEs were cerebral stroke and ischemia and MI. Discontinue necitumumab for serious or life-threatening VTE or ATE. The incidence of VTE may be higher in patients ≥70 years of age (compared to patients under age 70).
Disease-related concerns:
• Non-squamous NSCLC: Necitumumab is not indicated for use in patients with non-squamous NSCLC. In a study of necitumumab in combination with pemetrexed and cisplatin for the treatment of metastatic non-squamous NSCLC, patients experienced increased serious and fatal toxicities and cardiopulmonary arrest/sudden death within 30 days of the last dose of necitumumab (compared to pemetrexed and cisplatin without necitumumab).
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Portrazza is produced in genetically engineered mammalian NS0 cells.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Portrazza: 800 mg/50 mL (50 mL) [contains polysorbate 80]
No
Solution (Portrazza Intravenous)
800 mg/50 mL (per mL): $103.91
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Infuse over 60 minutes using an infusion pump. Infuse through a separate line. Flush with sodium chloride 0.9% at the end of infusion. Do not infuse with other medications or with electrolytes. Monitor for infusion reactions; reduce infusion rate by 50% for grade 1 infusion reaction; interrupt infusion for grade 2 infusion reaction.
Necitumumab should be administered prior to gemcitabine and cisplatin (Ref).
Non-small cell lung cancer (squamous), metastatic: First-line treatment of metastatic squamous non-small cell lung cancer (NSCLC) in combination with gemcitabine and cisplatin
Limitations of use: Not indicated for treatment of non-squamous NSCLC.
Necitumumab may be confused with bevacizumab, nivolumab, pembrolizumab, ramucirumab.
Portrazza may be confused with Arzerra.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Females of reproductive potential should use effective contraception during therapy and for 3 months after the last necitumumab dose.
Necitumumab is expected to cross the placenta. Based on the mechanism of action and data from animal reproduction studies, in utero exposure to necitumumab may cause fetal harm.
It is not known if necitumumab is present in breast milk; however, human IgG antibodies can be detected in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy or for 3 months after the last necitumumab dose.
Serum electrolytes, including magnesium, potassium, and calcium (prior to each dose during treatment and for at least 8 weeks following completion). Monitor for signs/symptoms of infusion-related reactions, dermatologic toxicity, and thromboembolism.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Necitumumab is a recombinant human IgG1 EGFR monoclonal antibody which binds (with a high affinity) to the ligand binding site of the EGFR receptor to prevent receptor activation and downstream signaling (Thatcher 2015).
Distribution: Vdss: 7 L.
Half-life elimination: ~14 days.
Excretion: Clearance (mean): 14.1 mL/hour.
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