Erbitux

Avoid exposure to sunlight or tanning beds while you are receiving cetuximab and for at least 2 months after your treatment ends. Cetuximab can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

There may be other drugs that can interact with cetuximab. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Erbitux is a prescription medication used to treat cancers of the colon and rectum. It is also used to treat head and neck cancer. This medication may be used in combination with other medicines or radiation therapy. Erbitux belongs to a group of drugs called epidermal growth factor receptor (EGFR) antagonists, which inhibit cancer cells from growing.

This medication comes in an injectable form and is to be injected intravenously (into a vein) at a hospital or clinic. It is usually given once a week.

Common side effects of Erbitux include acne-like rash, dry or cracking skin, and hair loss.

You should not use this medication if you are allergic to cetuximab or to mouse protein.

To make sure you can safely receive cetuximab, tell your doctor if you have any of these other conditions:

• heart rhythm problems;
• lung disease or a breathing disorder;
• congestive heart failure;
• coronary artery disease (clogged arteries); or
• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

FDA pregnancy category C. It is not known whether cetuximab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Whether you are a man or a woman, use effective birth control to prevent pregnancy while you are receiving cetuximab, and for at least 6 months after your treatment ends.

It is not known whether cetuximab passes into breast milk or if it could harm a nursing baby. You should not breast-feed a baby while you are receiving cetuximab and for at least 60 days after your treatment ends. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

Call your doctor for instructions if you miss an appointment for your cetuximab infusion.

Your doctor or pharmacist can provide more information about cetuximab.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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You should not use this medicine if you are allergic to cetuximab or to mouse protein.

To make sure cetuximab is safe for you, tell your doctor if you have:

• heart rhythm problems;

• lung disease or a breathing disorder;

• congestive heart failure;

• coronary artery disease (clogged arteries); or

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Whether you are a man or a woman, use effective birth control to prevent pregnancy while you are receiving cetuximab, and for at least 6 months after your treatment ends.

You should not breast-feed a baby while you are receiving cetuximab and for at least 60 days after your treatment ends. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

Contraindications

• No known contraindications according to manufacturer.1

Warnings/Precautions

Warnings

Potential for serious infusion-related effects (e.g., rapid airway obstruction [bronchospasm, stridor, hoarseness], hypotension, shock, loss of consciousness, MI, cardiac arrest).1 (See Infusion-related Effects in Boxed Warning.) Infusion-related effects are severe (grade 3 or 4) in 2–5% of patients; fatal in less than 1 in 1000 patients.1 Approximately 90% of severe reactions occur in association with initial cetuximab infusion despite premedication with antihistamines.1

Monitor for signs of infusion reactions during and for 1 hour following each cetuximab infusion in a setting where resuscitation equipment and agents necessary to treat anaphylaxis are readily available.1 7 10 For patients experiencing infusion reactions requiring treatment, monitor until event has resolved.1 10

If grade 1 or 2 or nonserious grade 3 or 4 infusion-related reaction occurs, reduce infusion rate by 50%.1

If serious infusion-related effects occur, discontinue cetuximab immediately and permanently and initiate appropriate therapy (e.g., epinephrine, corticosteroids, IV antihistamines, bronchodilators, oxygen).1

Cardiopulmonary arrest and/or sudden death reported in patients with or without CAD, arrhythmia, and/or CHF receiving cetuximab/radiation combination therapy for treatment of squamous cell carcinoma of the head and neck.1 (See Cardiopulmonary Arrest in Boxed Warning.)

Carefully consider use of cetuximab and radiation therapy for treatment of head and neck cancer in patients with a history of CAD, CHF, or arrhythmias.1 Closely monitor serum electrolytes, including magnesium, potassium, and calcium, during and following cetuximab therapy.1

Serious cardiotoxicity requiring discontinuance of therapy also reported in patients with squamous cell carcinoma of the head and neck receiving cetuximab in combination with cisplatin and radiation therapy (see Use in Combination with Radiation Therapy and Cisplatin under Cautions).1

Interstitial lung disease, interstitial pneumonitis (fatal in one case), and exacerbation of preexisting fibrotic lung disease reported.1 4 6

If acute onset or exacerbation of pulmonary manifestations occurs, interrupt therapy.1 If interstitial lung disease is confirmed, permanently discontinue therapy.1

Safety of combination regimen consisting of cetuximab, radiation therapy, and cisplatin not established.1 Serious cardiotoxicity and death (secondary to pneumonia or unknown cause) reported in patients receiving this combination for treatment of locally advanced squamous cell carcinoma of the head and neck.1

Electrolyte abnormalities, including hypomagnesemia, hypocalcemia, and hypokalemia, have occurred.1 Hypomagnesemia reported in 55% of patients; severe (grade 3 or 4) in 6–17% of patients.1 Onset of hypomagnesemia and accompanying electrolyte abnormalities may occur from days to months following initiation of therapy.1 10 Manifestations of hypomagnesemia may include fatigue and hypocalcemia.23

Monitor for hypomagnesemia, hypocalcemia, and hypokalemia during and for ≥8 weeks following completion of therapy.1 Replete electrolytes as necessary; IV replacement therapy indicated in severe cases.1 10 23

Sensitivity Reactions

Acneiform rash reported in 76–88% of patients; severe in 1–17%.1 Generally appears within first 2 weeks of therapy and may resolve following discontinuance; however, may persist beyond 28 days.1

Skin drying/fissuring,1 paronychial inflammation,1 infectious sequelae (e.g., abscess formation, blepharitis, conjunctivitis, keratitis, cheilitis, cellulitis, Staphylococcus aureus sepsis),1 and hypertrichosis1 24 reported.1 Fatal toxic epidermal necrolysis also reported.27

Monitor for possible dermatologic effects and infectious complications.1 If severe acneiform rash occurs, reduce dosage or discontinue therapy.1 (See Dermatologic Toxicity under Dosage and Administration.)

Limit sun exposure.1 (See Advice to Patients.)

General Precautions

In clinical trials for colorectal cancer, testing for evidence of EGFR expression was required.1 However, some authorities state that routine EGFR expression testing is not recommended in patients with colorectal cancer and that patients should not be included or excluded from cetuximab therapy based solely on EGFR test results.31

Because expression of EGFR has been detected in nearly all head and neck cancers, EGFR testing was not required in these clinical trials.1

Monitor for dermatologic toxicity and infectious sequelae.1

Periodically monitor for hypomagnesemia and accompanying hypocalcemia and hypokalemia during and for ≥8 weeks following completion of therapy.1 10

Nonneutralizing anticetuximab antibodies detected in about 5% of patients.1 Incidence of antibody development not fully established, but there appears to be no effect on safety and efficacy of the drug.1

Specific Populations

Category C.1

Not known whether cetuximab is distributed into milk, but potential exists for distribution of IgG antibodies into milk.1 Discontinue nursing or the drug; if nursing is interrupted, do not resume for at least 60 days following last dose (due to long half-life).1 (See Half-life under Pharmacokinetics.)

Safety and efficacy not established in pediatric patients.1

In patients receiving monotherapy or combination therapy for colorectal cancer, no overall differences in safety and efficacy relative to younger adults.1

Insufficient experience in patients ≥65 years of age with head and neck cancer to determine whether they respond differently than younger adults.1

Common Adverse Effects

Dermatologic effects (e.g., rash, pruritus, nail changes), headache, diarrhea, infection.1

Combination therapy with irinotecan in patients with advanced colorectal cancer: Acneiform rash, asthenia/malaise, diarrhea, nausea.1

Monotherapy in patients with advanced colorectal cancer: Rash/desquamation, fatigue, abdominal pain, pain, dry skin, dyspnea, constipation.1

In combination with radiation therapy in patients with head and neck cancer: Acneiform rash; radiation dermatitis; weight loss; asthenia; nausea; elevated ALT, AST, and alkaline phosphatase.1

Cetuximab injection is given with radiation treatment and other medicines to treat cancer in the colon and rectal area, and cancer in the head and neck area. This medicine is usually given to patients who have already received other cancer treatments. Cetuximab should only be used in patients with metastatic (cancer that spreads to other parts of the body) colon or rectal cancer who have had a KRAS gene mutation test. This test helps the doctor decide whether the medicine will treat their cancer.

Cetuximab interferes with the growth of cancer cells, which are then destroyed by the body. Since the growth of normal body cells may also be affected by cetuximab, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, such as a skin rash, may not be serious but may cause concern. Some effects do not occur until months or years after the medicine is used.

Before you begin treatment with cetuximab, you and your doctor should talk about the benefits this medicine will do as well as the risks of using it.

This medicine will only be given by or under the immediate supervision of your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of cetuximab injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of cetuximab injection in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Congestive heart failure, history of or
• Coronary artery disease, history of or
• Heart rhythm problems—May increase your risk of having serious side effects.

• Fibrotic lung disease, history of or
• Hypocalcemia (low calcium in the blood) or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood)—Use with caution. May make these conditions worse.

• If you have an allergy to cetuximab or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding. Do not breast-feed while you take Erbitux or for 2 months after your last dose.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Erbitux® is indicated in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. [See Clinical Studies (14.1).]

Erbitux is indicated in combination with platinum-based therapy with 5-FU for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck. [See Clinical Studies (14.1).]

Erbitux, as a single agent, is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed. [See Clinical Studies (14.1).]

K-Ras Wild-type, EGFR-expressing Colorectal Cancer

Erbitux is indicated for the treatment of K-Ras wild-type, epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer (mCRC) as determined by FDA-approved tests for this use [see Dosage and Administration (2.2), Warnings and Precautions (5.7), Clinical Studies (14.2)]:

• in combination with FOLFIRI (irinotecan, 5-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. [See Warnings and Precautions (5.7), Clinical Pharmacology (12.1), Clinical Studies (14.2).]

Limitation of Use: Erbitux is not indicated for treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown [see Warnings and Precautions (5.7), Clinical Studies (14.2)].

100 mg/50 mL, single-use vial

200 mg/100 mL, single-use vial

The maximum single dose of Erbitux administered is 1000 mg/m2 in one patient. No adverse events were reported for this patient.

Erbitux is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. The injection must be given slowly, and the IV infusion can take up to 2 hours to complete. You may be given other medications to prevent certain side effects while you are receiving cetuximab.

Erbitux is usually given once every week for 6 to 7 weeks or until your body no longer responds to the medication. Follow your doctor's dosing instructions very carefully.

Erbitux is often used in combination with other cancer medications and/or radiation treatments. You may receive another cancer medicine 1 hour after your cetuximab injection.

If you are also being treated with radiation, you will receive your first Erbitux injection 1 week before your radiation treatment. Later doses are usually given 1 hour before radiation treatments.

Cetuximab has caused life-threatening side effects in a small number of patients. After each infusion, your caregivers will watch you closely to make sure you do not have any serious side effects.

To make sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Erbitux can have long lasting effects on your body. You may need to have blood tests for several weeks after your Erbitux treatment has ended. Do not miss any follow-up visits to your doctor.

Usual Adult Dose for Colorectal Cancer:

Initial Dose: 400 mg/m2 administered as a 2 hour intravenous infusion (maximum infusion rate 5 mL/min)

Maintenance Dose: 250 mg/m2 infused over 1 hour (maximum infusion rate 5 mL/min) once a week

If given in combination with FOLFIRI, the Erbitux infusion should be completed one hour prior to FOLFIRI.

Usual Adult Dose for Squamous Cell Carcinoma:

Note: In combination with radiation therapy, Erbitux is approved by the FDA for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. In combination with platinum based therapy with 5-FU, Erbitux is indicated for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck. As a single agent, Erbitux is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum based therapy has failed.

As a Part of Combination Therapy:
Initial Loading Dose: 400 mg/m2 as a 120 minute intravenous infusion (maximum infusion rate 5 mL/min) one week prior to initiation of a course of radiation therapy or on the day of initiation of platinum based therapy with 5-FU.
Weekly Maintenance Dose: 250 mg/m2 infused over 60 minutes (maximum infusion rate 5 mL/min) weekly for the duration of radiation therapy (6 to 7 weeks) or until disease progression or unacceptable toxicity when administered in combination with platinum based therapy with 5-FU. Complete Erbitux administration 1 hour prior to radiation therapy or platinum based therapy with 5-FU.

Single Agent Therapy:
Initial Dose: 400 mg/m2 as a 120 minute intravenous infusion.
Weekly Maintenance Dose: 250 mg/m2, as a 60 minute intravenous infusion, weekly until disease progression or unacceptable toxicity occurs.

Call your doctor for instructions if you miss an appointment for your Erbitux infusion.