cetuximab (Rx)

Brand and Other Names:Erbitux
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution, single-use vial

  • 100mg/50mL (2mg/mL)
  • 200mg/100mL (2mg/mL)
more...

Colorectal Cancer

See also Administration

Indications

  • Indicated for treatment of KRAS mutation-negative (wild-type), epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer as determine by FDA-approved tests
  • In combination with FOLFIRI for first-line treatment OR
  • In combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy OR
  • As a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan

Dosage

  • Dosage is for either monotherapy or in combination
  • Initial dose: 400 mg/m² IV infuse over 2 hr  
  • Subsequent doses: 250 mg/m² IV infuse over 60 min qWeek (not to exceed an infusion rate of 10 mg/min) until disease progression or unacceptable toxicity
  • Complete cetuximab administration 1 hr prior to FOLFIRI
  • Not to exceed infusion rate of 10 mg/min

Head & Neck Cancer

See also Administration

Indications

  • Indicated in combination with radiation therapy for initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck
  • Also, indicated in combination with platinum-based therapy with 5-FU for first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
  • Monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed

Initial dose: 400 mg/m² IV infuse over 2 hr 

Subsequent doses: 250 mg/m²/week; infuse over 60 minutes (not to exceed an infusion rate of 10 mg/min) until disease progression or unacceptable toxicity

With radiation: Initiate 1 week prior to beginning radiation therapy, continue qWeek x 6-7 weeks

With platinum-based therapy with 5-FU: Initiate on the day beginning chemotherapy; complete cetuximab infusion 1 hr prior to administering platinum-based therapy with 5-FU

Dosage modifications

Infusion-related reactions

  • Grade 1 or 2: Reduce infusion rate by 50%
  • Grade 3 or 4: Immediately and permanently, discontinue cetuximab
  • Serious infusion reactions, requiring medical intervention and/or hospitalization: Immediately and permanently discontinued

Dermatologic toxicities and infectious sequelae (eg, acneiform rash, mucocutaneous disease)

  • First occurrence, Grade 3-4: Delay infusion 1-2 weeks; if condition improves, continue at 250 mg/m² if no improvement, discontinue cetuximab
  • Second occurrence, Grade 3-4: Delay infusion 1-2 weeks; if condition improves, continue at 200 mg/m² if no improvement, discontinue cetuximab
  • Third occurrence, Grade 3-4: Delay infusion 1-2 weeks; if condition improves, continue at 150 mg/m² if no improvement, discontinue cetuximab
  • Fourth occurrence: Discontinue cetuximab

Pulmonary toxicity

  • Acute onset or worsening pulmonary symptoms: Delay infusion 1-2 weeks; if condition improves, 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 cetuximab

Dosing Considerations

Limitation of use: Not indicated for treatment of Ras mutant colorectal cancer or when the results of the Ras mutation tests are unknown

Premedication

  • Premedicate with an H1 antagonist (eg, diphenhydramine 50 mg) IV 30-60 min before first dose; administer premedication subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions

Safety and efficacy not established

Next:

Adverse Effects

Adverse effects listed are all grades of severity unless indicated otherwise

>10% (Monotherapy)

Rash/desquamation (95%)

Fatigue (91%)

Nausea (64%)

Other pain (59%)

Dry skin (57%)

Constipation (53%)

Dyspnea (49%)

Pruritus (47%)

Sensory neuropathy (45%)

Diarrhea (42%)

Vomiting (40%)

Headache (38%)

Infections with neutropenia (38%)

Other dermatology (35%)

Stomatitis (32%)

Fatigue (31%)

Nail changes (31%)

Insomnia (27%)

Fever (25%)

Other gastrointestinal (22%)

Infusion reactions (18%)

Confusion (18%)

Other pain, Grade 3 or 4 (18%)

Rigors or chills (16%)

Dyspnea, Grade 3 or 4 (16%)

Rash/desquamation, Grade 3 or 4 (16%)

Anxiety (14%)

Depression (14%)

Dehydration (13%)

Mouth dryness (12%)

Other gastrointestinal, Grade 3 or 4 (12%)

Infections with neutropenia, Grade 3 or 4 (11%)

>10% (Combination Therapy)

Acne-like rash (86%)

Diarrhea (66%)

Neutropenia (49%)

Rash (44%)

Stomatitis (31%)

Anorexia (30%)

Pyrexia (26%)

Acneform dermatitis (26%)

Paronychia (20%)

Palmar-plantar erythrodysesthesia syndrome (19%)

Skin fissure (19%)

Conjunctivitis (18%)

Acne-like rash, Grade 3 or 4 (18%)

Diarrhea, Grade 3 or 4 (16%)

Dyspepsia (16%)

Decreased weight (15%)

Infusion-related reaction (14%)

Acne (14%)

Pruritus (14%)

1-10% (Monotherapy)

Taste disturbance (10%)

Nausea (6%)

Confusion, Grade 3 or 4 (6%)

Vomiting, Grade 3 or 4 (5%)

Bone pain (4%)

Infusion reactions, Grade 3 or 4 (3%)

Fever, Grade 3 or 4 (3%)

Constipation, Grade 3 or 4 (3%)

Arthralgia, Grade 3 or 4 (3%)

Diarrhea, Grade 3 or 4 (2%)

Pruritus, Grade 3 or 4 (2%)

Headache, Grade 3 or 4 (2%)

Rigors or chills, Grade 3 or 4 (1%)

Stomatitis, Grade 3 or 4 (1%)

1-10% (Combination Therapy)

Rash, Grade 3 or 4 (9%)

Acneform dermatitis, Grade 3 or 4 (5%)

Palmar-plantar erythrodysesthesia syndrome, Grade 3 or 4 (4%)

Stomatitis, Grade 3 or 4 (3%)

Anorexia, Grade 3 or 4 (3%)

Acne, Grade 3 or 4 (2%)

Skin fissures, Grade 3 or 4 (2%)

Infusion-related reactions, Grade 3 or 4 (1%)

Decreased weight, Grade 3 or 4 (1%)

Pyrexia, Grade 3 or 4 (1%)

Postmarketing Reports

Aseptic meningitis

Mucosal inflammation

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Life-threatening and fatal bullous mucocutaneous disease

Previous
Next:

Warnings

Black Box Warnings

Infusion reactions

  • Severe infusion reactions occurred with this agent in ~3% of patients in clinical trials, with fatal outcome reported in less than 1 in 1000
  • Immediately interrupt and permanently discontinue cetuximab infusion for serious infusion reactions (see Dosage Modifications)

Cardiopulmonary arrest

  • Cardiopulmonary arrest and/or sudden death occurred in 2% (4/208) of patients with squamous cell carcinoma of the head and neck treated with radiation therapy and cetuximab
  • Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after cetuximab therapy

Contraindications

None

Cautions

Use in colorectal cancer only with confirmed KRAS mutation negative (wild-type); confirm Ras mutation status in tumor specimens prior to initiating therapy

Risk of cardiopulmonary arrest and sudden death (see Black Box Warnings)

Increases risk of electrolyte depletion, especially hypomagnesemia; hypomagnesemia and accompanying electrolyte abnormalities can occur days to months after initiating therapy; monitor patients weekly during treatment for hypomagnesemia; hypomagnesemia of any grade reported in 4% of patients receiving cetuximab, carboplatin, and fluorouracil; periodically monitor during and for at least 8 wk following completion of therapy; replete electrolytes as necessary

Risk of anaphylactic reactions may increase in patients with a history of tick bites, red meat allergy, or in the presence of IgE antibodies directed against galactose-α-1,3-galactose (alpha-gal)

Risk of infusion reactions; monitor patients following infusion; discontinue therapy for serious infusion reactions (see Black Box Warnings)

Mucocutaneous adverse reactions may occur; limit sun exposure; wear sunscreen and hats

Dermatologic toxicities (eg, life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, skin sloughing, acneiform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae [eg, Streptococcal aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis/ulcerative keratitis with decreased visual acuity, cheilitis], hypertrichosis); monitor for inflammatory or infectious sequelae

Increased incidence of grade 3-4 mucositis, radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances when used in combination with radiation and cisplatin; coadministration did not improve progression-free survival

Interstitial lung disease reported; interrupt treatment for acute onset or worsen of pulmonary symptoms; monitor patients for signs and symptoms of pulmonary toxicity

Increased tumor progression, increased mortality, or lack of benefit in patients with Ras-mutant metastatic colorectal cancer (mCRC)

Fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Previous
Next:

Pregnancy & Lactation

Pregnancy

Based on findings from animal studies and its mechanism of action, cetuximab can cause fetal harm when administered to pregnant women

There are no available data in pregnant women; advise pregnant women of the potential risk to a fetus

Verify pregnancy status in females of reproductive potential prior to initiating treatment

Animal data

  • In an animal reproduction study, IV administration of cetuximab once weekly to pregnant cynomolgus monkeys during the period of organogenesis resulted in an increased incidence of embryo lethality and abortion
  • 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
  • Human IgG is known to cross the placental barrier; therefore, cetuximab may be transmitted from the mother to the developing fetus

Contraception

  • Advise females of reproductive potential to use effective contraception during treatment and for 2 months after last dose

Infertility

  • Based on animal studies, cetuximab may impair fertility in females of reproductive potential

Lactation

There is no information regarding the presence of drug in human milk, the effects on the breastfed infant, or the effects on milk production

Human IgG antibodies can be excreted in human milk

Due to potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 2 months after last 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.

more...
Previous
Next:

Pharmacology

Mechanism of Action

Recombinant humanized monoclonal antibody

Binds specifically to the EGF receptor (EGFR, HER1, c-ErbB-1) on both normal and tumor cells

Competitively inhibits the binding of EGF NS other ligands, such as TGF-alpha

Blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, NS decreased matrix metalloproteinase ns VEGF production

Absorption

AUC: Increased in a greater than dose proportional manner as dose increased from 20 to 400 mg/m²

Peak Plasma Concentration

  • Following a 2 hr infusion of 400 mg/m²: 184 mcg/mL (range: 92-327 mcg/mL)
  • Following a 1 hr infusion of 250 mg/m²: 140 mcg/mL (range 120-170 mcg/mL)

Distribution

Vd: 2-3 L/m²

Elimination

Half-life: 114 hr (range 75-188 hr); 97 hr (range 41-213 hr), following 400 mg/sq.meter IV over 2 hr

Clearance: Decreased from 0.08 to 0.02 L/hr/sq.meter as dose increased from 20 to 200 mg/m² plateaus at doses >200 mg/m²

Pharmacogenomics

Colorectal cancer

  • Colorectal cancer expressing with KRAS wild-type respond more favorably to regimens that include anti-EGFR antibodies (cetuximab, panitumumab); whereas, the presence of KRAS mutation (codon 12 or 13) showed an absence of biological and clinical activity for the anti-EGFR antibody treatment
  • Strongly recommended that patients with metastatic CRC who are being considered for treatment with anti-EGFR antibody therapy should be tested for the presence of a KRAS mutation prior to the administration of therapy (NCCN guidelines)

Non-small cell lung cancer (investigational)

  • Presence of EGFR mutations does not appear to predict response to treatment with the EGFR monoclonal antibody cetuximab, but clinical trials have been conflicting
  • An ongoing study is underway to examine prospectively whether high EGFR protein expression can be used as a predictor of treatment response to cetuximab

Genetic testing laboratories

  • The following companies are currently offering KRAS mutation status testing
  • Clarient, Inc. (http://www.clarientinc.com)
  • Caris Diagnostics (http://www.carisdx.com)
  • DxS (http://www.dxsdiagnostics.com)
  • Genzyme Genetics (http://www.genzymegenetics.com)
  • LabCorp (http://www.labcorp.com)
  • Response Genetics (http://www.responsegenetics.com)
Previous
Next:

Administration

IV Preparation

Do not shake or dilute

Discard unused portion after 8 hr at room temp & 12 hr if refrigerated

IV Administration

Do not administer as an IV push or bolus

Administer via infusion pump or syringe pump IV infusion: initial dose over 2 hr and weekly maintenance dose over 1 hr

Do not exceed an infusion rate of 10 mg/min

Administer through low protein binding 0.22-micrometer in-line filter

Visually inspect for particulate matter and discoloration prior to administration; solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates

Do not shake or dilute

Premedication

  • Premedicate with an H1 antagonist (eg, diphenhydramine 50 mg) IV 30-60 min prior to the first dose; administer premedication subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions

Storage

Unused vials

  • Refrigerate at 2-8°C (36-46°F); do not freeze
  • Increased particulate formation may occur at temperatures ≤0°C

Prepared infusions

  • Refrigerate at 2-8°C (36-46°F) for up to 12 hr OR
  • Store at room temperature (20-25°C [68-77°F]) for up to 8 hr
  • Discard any remaining solution in the infusion container after 8 hr at room temperature or after 12 hr refrigerated
Previous
Next:

Images

Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous
Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.