Version July 2025
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.
Dosage guidance:
Safety: For patients with a prior grade 1 or 2 infusion reaction, premedicate with diphenhydramine (or equivalent) prior to all subsequent necitumumab infusions. For patients with a recurrent grade 1 or 2 infusion reaction, premedicate with diphenhydramine (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to all subsequent necitumumab infusions.
Non–small cell lung cancer, metastatic, squamous: IV: 800 mg on days 1 and 8 of each 3-week treatment cycle (in combination with gemcitabine and cisplatin for a maximum of 6 cycles), followed by necitumumab (as a single agent) until disease progression or unacceptable toxicity (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); 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 (has not been studied); 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).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Note: Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
|
Adverse reaction |
Severity |
Necitumumab dosage modification |
|---|---|---|
|
Dermatologic toxicity |
Grade 3 rash or acneiform rash |
Withhold necitumumab until symptoms resolve to ≤ grade 2; 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. Rash does not resolve to ≤ grade 2 within 6 weeks: Permanently discontinue necitumumab. Rash worsens or is intolerable at the 400 mg dose: Permanently discontinue necitumumab. |
|
Grade 3 skin induration or fibrosis |
Permanently discontinue necitumumab. | |
|
Grade 4 dermatologic toxicity |
Permanently discontinue necitumumab. | |
|
Electrolyte abnormality |
Grade 3 or 4 |
Replete electrolytes as appropriate. Withhold necitumumab until electrolyte abnormality has improved to ≤ grade 2. |
|
Infusion-related reactions |
Grade 1 |
Reduce necitumumab infusion rate by 50%. First occurrence: Premedicate with diphenhydramine (or equivalent) prior to all subsequent infusions. Second and subsequent occurrences: Premedicate with diphenhydramine (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to all subsequent infusions. |
|
Grade 2 |
Interrupt necitumumab infusion until resolution to grade 1 or 0; resume necitumumab with infusion rate reduced by 50% for all subsequent infusions. First occurrence: Premedicate with diphenhydramine (or equivalent) prior to all subsequent infusions. Second and subsequent occurrences: Premedicate with diphenhydramine (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to all subsequent infusions. | |
|
Grade 3 or 4 |
Permanently discontinue necitumumab. | |
|
Thromboembolic events (arterial or venous thromboembolism) |
Serious or life-threatening |
Discontinue 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: Cardiopulmonary arrest and/or sudden death occurred in a small percentage of patients treated with necitumumab in combination with gemcitabine and cisplatin. 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, myocardial infarction (MI) within 6 months, uncontrolled hypertension or uncontrolled heart failure were excluded from the squamous cell non-small cell lung cancer (NSCLC) study. The risk of cardiopulmonary arrest or sudden death in patients with a history of coronary artery disease, heart failure, or arrhythmias as compared to those without these comorbid conditions is unknown.
• 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. Patients should minimize exposure to the sun.
• Hypomagnesemia: Hypomagnesemia occurred in a majority of patients receiving necitumumab in combination with gemcitabine and cisplatin; hypomagnesemia was severe in one-fifth of patients. 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.
• 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. In a clinical study, the relative risk of VTE or ATE was approximately 3-fold higher in patients with a history of VTE or ATE compared to those without a reported history.
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).
Special populations :
• Older adults: The incidence of VTE, including pulmonary embolism, may be higher in patients ≥70 years of age (compared to patients <70 years of age).
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: Administer 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.
Administration sequence (for combination therapy): In combination with cisplatin and gemcitabine: Administer necitumumab first, followed by gemcitabine and cisplatin (Ref).
Non-small cell lung cancer, metastatic, squamous: First-line treatment of metastatic squamous non-small cell lung cancer (NSCLC) in combination with gemcitabine and cisplatin
Limitations of use: Necitumumab is not indicated for treatment of non-squamous NSCLC.
Necitumumab may be confused with bevacizumab, naxitamab, nimotuzumab, nivolumab, pembrolizumab, ramucirumab.
Portrazza may be confused with Arzerra.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Patients who could become pregnant 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 of necitumumab treatment). Monitor for signs/symptoms of infusion-related reactions (during and after infusion), 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.
