Dosing and uses of Portrazza (necitumumab)
Adult dosage forms and strengths
IV solution
- 800mg/50mL (16mg/mL)
Non-small Cell Lung Cancer
Indicated for first-line treatment of metastatic squamous NSCLC in combination with gemcitabine and cisplatin
800 mg IV infused over 1 hr on days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion
Continue therapy until disease progression or unacceptable toxicity
Dosage modifications
Infusion-related reactions
- Grade 1: Reduce the infusion rate by 50%
- Grade 2: Stop the infusion until signs and symptoms have resolved to grade 0 or 1; resume infusion at 50% reduced rate for all subsequent infusions
- Grade 3 or 4 IRR: Permanently discontinue
- Also see Administration
Dermatologic toxicity
- Grade 3 rash or acneiform rash: Withhold until symptoms resolve to grade ≤2, then resume infusion 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 if
- Grade 3 rash or acneiform rash do not resolve to grade ≤2 within 6 wk
- Reactions worsen or become intolerable at a dose of 400 mg
- Patient experiences grade 3 skin induration/fibrosis
- Grade 4 dermatologic toxicity
Dosing Considerations
Limitations of use: Not indicated for treatment of nonsquamous NSCLC
Pediatric dosage forms and strengths
Safety and efficacy not established
Portrazza (necitumumab) adverse (side) effects
Percentages listed below are for all grades of toxicity unless otherwise noted
>10%
Hypomagnesemia (83%)
Hypocalcemia (45%)
Rash (44%)
Hypocalcemia (albumin corrected) (36%)
Hypophosphatemia (31%)
Vomiting (29%)
Hypokalemia (28%)
Hypomagnesemia, grade 3-4 (20%)
Diarrhea (16%)
Dermatitis acneiform (15%)
Weight decreased (13%)
Stomatitis (11%)
Headache (11%)
1-10%
Hemoptysis (10%)
Venous thromboembolic events (9%)
Acne (9%)
Hypophosphatemia, grade 3-4 (8%)
Paronychia (7%)
Conjunctivitis (7%)
Pruritus (7%)
Dry skin (7%)
Hypocalcemia, grade 3-4 (6%)
Hypokalemia, grade 3-4 (5%)
Skin fissures (5%)
Pulmonary embolism (5%)
Venous thromboembolic events, grade 3-4 (5%)
Hypocalcemia (albumin corrected), grade 3-4 (4%)
Vomiting, grade 3-4 (3%)
Diarrhea, grade 3-4 (2%)
Stomatitis, grade 3-4 (1%)
Warnings
Black box warnings
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 (administer drug through dedicated IV line; do not mix with electrolyte or dextrose solutions) (see 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 during treatment and for at least 8 weeks following completion
Withhold drug for grade 3 or 4 electrolyte abnormalities
Replete electrolytes as medically appropriate
Contraindications
None
Cautions
Cardiopulmonary arrest reported in 3% of patients with necitumumab plus gemcitabine and cisplatin compared with 0.6% with gemcitabine and cisplatin; closely monitor serum electrolytes during and after dose
Monitor for hypomagnesemia (see Black box warnings)
Discontinue if severe venous or arterial thrombosis occurs
Dermatologic toxicities, including rash, dermatitis acneiform, acne, dry skin, pruritus, generalized rash, skin fissures, maculopapular rash and erythema, occurred in 79% of patients, typically within the first 2 weeks of therapy; limit sun exposure and discontinue for severe toxicity (see Dosage modifications)
Infusion-related reactions may occur; discontinue for severe reactions (see Dosage modifications)
Not indicated for nonsquamous NSCLC; increased toxicity and increased mortality occurred when necitumumab was added to pemetrexed and cisplatin therapy for these patients
Based on animal data and its mechanism of action, can cause fetal harm when administered to a pregnant woman (see Pregnancy)
Pregnancy
Pregnancy
Based on animal data and its mechanism of action, can cause fetal harm when administered during pregnancy
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for 3 months following the final dose
Animal studies
- 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 postnatal death in animals
Lactation
Unknown if distributed in human breast milk
Advise a nursing woman not to breastfeed during treatment and for 3 months following the final dose
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Portrazza (necitumumab)
Mechanism of action
Epidermal growth factor receptor (EGFR) inhibitor; monoclonal antibody that binds to the human EFGR and blocks interaction between EGFR and its ligands
Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis
Pharmacokinetics
Time to steady state: ~100 days
Total systemic clearance at steady-state: 14.1 mL/hr
Vd: 7 L
Half-life: ~14 days
Administration
IV Compatibilities
0.9% NaCL
IV Incompatibilities
Dextrose-containing solutions
Electrolyte-containing solutions
IV Preparation
Inspect vial contents for particulate matter and discoloration prior to dilution
Discard vial if particulate matter or discoloration is identified
Dilute the required dosage volume with 0.9% NaCl in an IV infusion container to a final volume of 250 mL
Do not use solutions containing dextrose
Do not dilute with other solutions or coinfuse with other electrolytes or medication
Gently invert the container to ensure adequate mixing (do not shake)
IV Administration
Administer diluted solution via infusion pump over 1 hr through a separate infusion line
Flush line with 0.9% NaCl at the end of the infusion
Premedication
- For patients who have experienced a previous grade 1 or 2 infusion-related reaction (IRR), premedicate with diphenhydramine (or equivalent) prior to all subsequent necitumumab infusions
- For patients who have experienced a second grade 1 or 2 occurrence of IRR, premedicate for all subsequent infusions with diphenhydramine (or equivalent), acetaminophen, and dexamethasone (or equivalent) prior to each necitumumab infusion
- Also see Dosage modifications
Storage
Unopened vials
- Store vials in a refrigerator at 2-8°C (36-46˚F) until time of use
- Keep the vial in the outer carton in order to protect from light
Diluted drug
- Do not freeze
- Do not shake the infusion solution
- Store diluted infusion solution for no more than 24 hr at 2-8°C (36-46°F), or no more than 4 hr at room temperature (up to 25°C [77°F])
- Discard vial with any unused portion of necitumumab
