Necitumumab

Serious side effects have been reported with necitumumab. See the "necitumumab Precautions" section.

Common side effects of necitumumab include the following:

• low magnesium levels and/or other electrolytes (calcium, potassium, and phosphate) in the blood
• rash
• vomiting
• diarrhea

This is not a complete list of necitumumab side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Before taking necitumumab, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to necitumumab or to any of its ingredients
• have a history of heart problems
• have a history of high blood pressure
• have a history of lung problems (COPD)
• have or are at high risk for blood clots
• are pregnant or may become pregnant
• are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take necitumumab exactly as prescribed.

This medication is available as a solution to be given into the vein (IV) by a healthcare professional.

Your doctor may also give you other medications before your necitumumab infusion to help manage possible side effects.

• 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.

Call your doctor for instructions if you miss an appointment for your necitumumab injection.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include headache, nausea, or vomiting.

Usual Adult Dose for Non-Small Cell Lung Cancer:

800 mg IV over 60 minutes on Days 1 and 8 of each 3 week cycle prior to gemcitabine and cisplatin infusion

Duration of therapy: Continue until disease progression or unacceptable toxicity

Premedication
-For patients who have experienced a previous Grade 1 or 2 infusion-related reaction (IRR), premedicate with diphenhydramine (or equivalent) prior to all infusions of this drug.
-For patients who have experienced a second Grade 1 or 2 occurrence of IRR, premedicate for all subsequent infusions, with diphenhydramine (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to each infusion of this drug.

Use: This drug is indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer

Antineoplastic agent; a recombinant, fully human IgG1 kappa monoclonal antibody that binds to human epidermal growth factor receptor (EGFR).1 2 4 5 6

General

Premedication for Infusion-related Reactions

• In patients who previously experienced a grade 1 or 2 infusion-related reaction to necitumumab, premedicate with an antihistamine (e.g., diphenhydramine or equivalent) prior to each subsequent infusion.1

• Following a second occurrence of a grade 1 or 2 infusion-related reaction, premedicate with an antihistamine (e.g., diphenhydramine or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to each subsequent infusion.1 (See Infusion-related Reactions under Dosage and Administration and also under Cautions.)

Serum Electrolyte Monitoring

• Closely monitor serum electrolyte concentrations, including magnesium, potassium, and calcium, and aggressively correct electrolyte abnormalities as clinically appropriate prior to each necitumumab infusion and for ≥8 weeks following the last dose.1 (See Electrolyte Abnormalities under Dosage and Administration.)

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion via an infusion pump.1

Necitumumab injection concentrate must be diluted prior to administration.1 Use within 4 hours following dilution if stored at room temperature or within 24 hours if stored at 2–8°C.1 (See Storage under Stability.)

Do not administer with any other drug or electrolytes simultaneously in the same IV line.1

Flush IV line with 0.9% sodium chloride injection at end of infusion.1

Withdraw appropriate volume of necitumumab injection concentrate from vial labeled as containing 800 mg in 50 mL and add to infusion container containing the appropriate volume of 0.9% sodium chloride injection to yield a final volume of 250 mL.1 Mix by gentle inversion; do not shake.1

Do not dilute in dextrose-containing or other solutions or admix with any other drug or electrolytes.1

Discard any partially used vials.1

Administer over 60 minutes.1

Dosage

Adults

800 mg on days 1 and 8 of each 3-week cycle; use in combination with gemcitabine and cisplatin.1

Administer necitumumab prior to IV infusion of gemcitabine and cisplatin.1

Continue therapy until disease progression or unacceptable toxicity occurs.1

If grade 1 infusion-related reaction occurs, reduce infusion rate by 50%.1

If grade 2 infusion-related reaction occurs, interrupt infusion until resolution to grade 1 or less; resume at 50% reduced rate for subsequent infusions.1

If grade 3 or 4 infusion-related reaction occurs, permanently discontinue therapy.1 (See Infusion-related Reactions under Cautions.)

If grade 3 rash or acneiform rash develops, interrupt therapy.1 If toxicity improves to grade 2 or less, resume necitumumab at reduced dosage of 400 mg for at least 1 cycle.1 May increase dosage to 600 mg, then to 800 mg in subsequent cycles if symptoms do not worsen.1 If dermatologic toxicity worsens or becomes intolerable at a dosage of 400 mg, permanently discontinue therapy.1 If grade 3 rash or acneiform rash does not improve to grade 2 or less within 6 weeks, permanently discontinue therapy.1

If grade 3 skin induration/fibrosis or grade 4 dermatologic toxicity occurs, permanently discontinue therapy.1 (See Dermatologic Toxicity under Cautions.)

If grade 3 or 4 electrolyte abnormalities occur, interrupt therapy.1 Resume therapy at previous dosage upon improvement of hypomagnesemia and related electrolyte abnormalities to grade 2 or less.1 (See Cardiopulmonary Arrest and also see Hypomagnesemia under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations at this time.1 (See Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations at this time.1 (See Geriatric Use under Cautions.)

Body Weight, Race, and Gender

No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Absorption

Bioavailability

Steady-state concentrations predicted to be reached approximately 100 days following IV infusion of necitumumab 800 mg on days 1 and 8 of each 21-day cycle.1

Special Populations

Systemic exposure not affected by renal function in a population pharmacokinetic analysis.1

Systemic exposure not affected by mild or moderate hepatic impairment in a population pharmacokinetic analysis.1 Patients with severe hepatic impairment not enrolled in clinical trials.1

Gender, age (range: 19–84 years), and race do not substantially affect systemic exposure.1

Effect of body weight on necitumumab exposure not clinically important.1 (See Special Populations under Dosage and Administration.)

Distribution

Extent

Not known whether necitumumab distributes into milk.1

Elimination

Half-life

Approximately 14 days.1

Storage

Parenteral

2–8°C.1 Keep vial in outer carton until time of use to protect from light; do not freeze or shake vial.1

Diluted infusion solution: Room temperature (≤25°C) for ≤4 hours or 2–8°C for ≤24 hours after dilution.1 Do not freeze or shake infusion solution.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Dilute in 0.9% sodium chloride.1

Do not dilute with dextrose-containing or other solutions or admix with other drugs or electrolytes.1

Parenteral

• Risk of electrolyte abnormalities, including hypomagnesemia, hypokalemia, and hypocalcemia.1 Importance of advising patients to take electrolyte replacement therapy exactly as advised by their clinician.1

• Risk of venous and arterial thromboembolic events.1

• Risk of skin reactions.1 Importance of minimizing sun exposure with protective clothing and use of sunscreen during therapy.1

• Risk of infusion-related reactions.1 Importance of informing patients to report signs and symptoms of infusion reactions (e.g., fever, chills, breathing problems) to a healthcare professional.1

• Risk of fetal harm.1 Advise women of childbearing potential to use effective methods of contraception while receiving necitumumab and for 3 months after the last dose.1 If pregnancy occurs, apprise patient of potential fetal hazard.1

• Importance of advising women to avoid breast-feeding during therapy and for 3 months following the last dose.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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 (Thatcher 2015).

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 (Thatcher 2015).

Refer to adult dosing.

Dermatologic toxicity:

Grade 3 rash or acneiform rash: Withhold 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.

Grade 3 rash or acneiform rash that worsens or is intolerable at the 400 mg dose: Permanently discontinue.

Grade 3 skin induration/fibrosis: Permanently discontinue.

Grade 4 dermatologic toxicity: Permanently discontinue.

Electrolyte abnormality: Grade 3 or 4 electrolyte abnormality: Withhold treatment; may resume when electrolyte abnormality has improved to grade 2 or lower (replete electrolytes as appropriate).

Infusion-related reactions:

Grade 1: Reduce infusion rate by 50%.

Grade 2: Interrupt 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.

Thromboembolic events: Serious or life-threatening VTE or ATE: Discontinue treatment.

Serum electrolytes, including magnesium, potassium, and calcium (prior to each dose during treatment and for at least 8 weeks following completion). Signs/symptoms of infusion-related reactions, dermatologic toxicity, and thromboembolism.

Use should be avoided. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: -Nursing women should be advised not to breastfeed during treatment with this drug and for 3 months following the final dose. -The effects in the nursing infant are unknown.