Usual Adult Dose for Colorectal Cancer

As a Single-Agent or in Combination with Irinotecan or FOLFIRI (irinotecan, fluorouracil, leucovorin)

• Administer weekly or biweekly as below; complete cetuximab administration 1 hour prior to irinotecan or FOLFIRI; continue treatment until disease progression or unacceptable toxicity

WEEKLY: Initial Dose: 400 mg/m2 IV over 120 minutes; Maintenance Dose: 250 mg/m2 IV over 60 minutes once a week
BIWEEKLY: 500 mg/m2 IV over 120 minutes every 2 weeks

In Combination with Encorafenib:
Initial Dose: 400 mg/m2 IV over 120 minutes
Maintenance Dose: 250 mg/m2 IV over 60 minutes once a week until disease progression or unacceptable toxicity

Comments:

• Patient selection for treatment requires testing for presence of K-Ras or BRAF V600E mutations; information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics
• This drug is not indicated for treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown
• Premedicate with an H1 antagonist IV 30 to 60 minutes prior to the first dose or subsequent doses as deemed necessary.
• Dose modifications may be necessary for adverse reactions (See Dosage Adjustment Section)

Uses: Colorectal Cancer:
For the treatment of K-Ras wild-type, epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer (mCRC) as determined by an FDA-approved test:

• In combination with FOLFIRI (irinotecan, fluorouracil, leucovorin) for first-line treatment
• In combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy
• As a single-agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.

For the treatment of mCRC in combination with encorafenib for patients with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy

Usual Adult Dose for Head and Neck Cancer

In Combination with Radiation Therapy: Complete IV administration 1 hour prior to radiation therapy

• Initial dose: 400 mg/m2 IV over 120 minutes administered 1 week prior to initiating a course of radiation therapy
• Maintenance dose: 250 mg/m2 IV over 60 minutes once a week for the duration of radiation therapy (6 to 7 weeks)

As a Single-Agent or In Combination with Platinum-Based Therapy and Fluorouracil:

• Administer weekly or biweekly as below; complete cetuximab administration 1 hour prior to platinum-based therapy with fluorouracil; continue treatment until disease progression or unacceptable toxicity

WEEKLY: Initial dose: 400 mg/m2 IV over 120 minutes; Maintenance dose: 250 mg/m2 IV over 60 minutes once a week
BIWEEKLY: 500 mg/m2 IV over 120 minutes every 2 weeks

Comments:

• Premedicate with an H1 antagonist IV 30 to 60 minutes prior to the first dose or subsequent doses as deemed necessary.
• Dose modifications may be necessary for adverse reactions (See Dosage Adjustment Section).

Uses: Squamous Cell Carcinoma of the Head and Neck (SCCHN):

• In combination with radiation therapy for the initial treatment of locally or regionally advanced SCCHN
• In combination with platinum-based therapy with fluorouracil for the first-line treatment of patients with recurrent locoregional disease or metastatic SCCHN
• As a single-agent for the treatment of patients with recurrent or metastatic SCCHN for whom prior platinum-based therapy has failed

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Dose Modifications for Adverse Reactions:
INFUSION REACTIONS:

• Grade 1 or 2: Reduce infusion rate by 50%.
• Grade 3 or 4: Immediately and permanently discontinue therapy.

DERMATOLOGIC TOXICITIES AND INFECTIOUS SEQUELAE (e.g., acneiform rash, mucocutaneous disease):

• First occurrence Grade 3 or 4: Delay infusion 1 to 2 weeks; if improvement, continue at 250 mg/m2; if no improvement, discontinue therapy.
• Second occurrence Grade 3 or 4: Delay infusion 1 to 2 weeks; if improvement, continue at 200 mg/m2; if no improvement, discontinue therapy.
• Third occurrence Grade 3 or 4: Delay infusion 1 to 2 weeks; if improvement, continue at 150 mg/m2; if no improvement, discontinue therapy.
• Fourth occurrence Grade 3 or 4: Discontinue therapy.

PULMONARY TOXICITY:

• Acute onset or worsening pulmonary symptoms: Delay infusion 1 to 2 weeks; if improvement, continue at the dose that was being administered at the time of occurrence; if no improvement in 2 weeks or interstitial lung disease (ILD) is confirmed, discontinue therapy.

For the dosage or recommended dose modifications of concomitantly used chemotherapeutic agents, refer to the product information for these products.

Precautions

US BOXED WARNINGS: INFUSION REACTIONS and CARDIOPULMONARY ARREST

• Infusion Reactions: This drug can cause serious and fatal infusion reactions. Immediately interrupt and permanently discontinue therapy for serious infusion reactions.
• Cardiopulmonary Arrest: Cardiopulmonary arrest or sudden death has occurred in patients with squamous cell carcinoma of the head and neck receiving this drug with radiation therapy or with platinum-based therapy and fluorouracil. Monitor serum electrolytes including serum magnesium, potassium, and calcium, during and after administration.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer via infusion pump or syringe pump at an infusion rate not to exceed 10 mg/min; do not administer as an IV push or bolus
• Complete cetuximab administration 1 hour prior to platinum-based therapy with fluorouracil, irinotecan or FOLFIRI
• Administer through a low protein binding 0.22-microliter in-line filter
• Administered under supervision of specialists with experience in prescribing antineoplastic agents, and in a setting where resuscitation equipment is available; see Dosage Adjustments for dose modifications based on infusion reactions
• Premedicate with a histamine-1 receptor antagonist IV 30 to 60 minutes prior to infusion
• A one hour observation period is recommended following the infusion; longer observation periods may be required in patients who experience reactions.

Preparation techniques:

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration; the solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates; do not use if solution is discolored, cloudy, or contains foreign particulate matter (an increase in particulate formation may occur at temperatures at or below 0C (32F)
• Do not shake or dilute

Storage:

• Store vials in refrigerator (36F to 46F [2C to 8C]); do not freeze or shake
• Once vial is opened, discard remaining solution after 8 hours at room temperature OR 12 hours at refrigerated temperature

General:

• This drug is not indicated for treatment of Ras-mutant colorectal cancer or when the result of the Ras mutation tests is unknown.
• Information on FDA-approved tests for the detection of K-Ras or BRAF V600E mutations is available at: http://www.fda.gov/CompanionDiagnostics.

Monitoring:

• Monitor serum electrolytes (serum magnesium, potassium, and calcium) during and for at least 8 weeks following treatment
• Monitor for infusion reactions for at least 1 hour following infusion in a setting equipped to treat anaphylaxis; longer surveillance is recommended if an infusion reaction occurs
• Monitor for dermatologic and respiratory toxicities

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling.
• Patients should understand the risk of serious infusion reactions and should be advised to report signs of infusion reactions including late onset infusion reactions.
• Patients should be advised to report new or worsening cough, chest pain, or shortness of breath.
• Patients should be advised to limit sun exposure during treatment and for 2 months after their last dose; patients should be advised to notify their healthcare provider of any sign of acne-like rash, conjunctivitis, blepharitis, or decreased vision.
• Female patients should be advised of risks to a fetus and counseled on use of contraception during treatment and for 2 months after their last dose; patients should be advised to avoid breastfeeding.