Medical Editor: John P. Cunha, DO, FACOEP
What Is Erbitux?
Erbitux (cetuximab), in combination with radiation therapy, is a monoclonal antibody indicated for the initial treatment of locally or regionally advanced head and neck cancer of a specific type (squamous cell carcinoma). Used alone, Erbitux is also approved to treat patients with head and neck cancers that have returned in the same location or spread to other parts of the body and for head and neck cancers that have progressed following platinum-based chemotherapy. Erbitux is also used on metastatic colorectal cancers that contain epidermal growth factor receptors.
What Are Side Effects of Erbitux?
The most common side effects of Erbitux include:
- rash,
- itching,
- dry or cracked skin,
- nail changes,
- headache,
- diarrhea,
- nausea,
- vomiting,
- upset stomach,
- weight loss,
- weakness, and
- respiratory, skin, and mouth infections.
Erbitux also can cause low blood magnesium, potassium, and calcium. Patients taking Erbitux should limit their exposure to the sun. Rare but serious side effects of Erbitux include:
- life-threatening allergic reactions and
- heart attacks, especially if the patient was also obtaining chemotherapy or radiotherapy.
Dosage for Erbitux
Erbitux is supplied at a concentration of 2 mg/mL in 100 mg (50 mL) or 200 mg (100 mL), single-use vials. Erbitux IV dosage and administration should only be done by those trained in the administration of this drug.
What Drugs, Substances, or Supplements Interact with Erbitux?
Erbitux may interact with other drugs. Tell your doctor all medications and supplements you use.
Erbitux During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant while using Erbitux; it is unknown if it will harm a fetus. Men and women should use birth control to prevent pregnancy while receiving Erbitux and for at least 6 months after treatment ends. It is unknown if Erbitux passes into breast milk or if it could harm a nursing baby. Breastfeeding is not recommended while receiving Erbitux and for at least 60 days after treatment ends.
Additional Information
Our Erbitux Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
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Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).
Some side effects may occur during the infusion or several hours afterward. Tell your caregiver right away if you feel short of breath, itchy, nauseated, weak or dizzy, or if you have chest pain, wheezing, noisy breathing, or a hoarse voice.
Call your doctor at once if you have:
- eye pain or redness, puffy eyelids, drainage or crusting in your eyes, vision problems, or increased sensitivity to light;
- a new or worsening cough, chest pain, or shortness of breath;
- an acne-like skin rash or any severe skin rash;
- redness or crusting around your hair follicles;
- redness, warmth, or puffiness under your skin;
- slow heartbeats, weak pulse, fainting, slow breathing (breathing may stop);
- blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
- low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing; or
- signs of an electrolyte imbalance--increased thirst or urination, constipation, muscle pain or weakness, leg cramps, numbness or tingling, feeling jittery, irregular heartbeats, fluttering in your chest, or a choking feeling.
Common side effects may include:
- itching or rash;
- changes in your fingernails or toenails;
- dry, cracked, or swollen skin;
- headache;
- diarrhea; or
- infection.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Erbitux (Cetuximab)
QUESTION
What are risk factors for developing colon cancer? See AnswerSIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the label:
- Infusion reactions [see WARNINGS AND PRECAUTIONS].
- Cardiopulmonary arrest [see WARNINGS AND PRECAUTIONS].
- Pulmonary toxicity [see WARNINGS AND PRECAUTIONS].
- Dermatologic toxicity [see WARNINGS AND PRECAUTIONS].
- Hypomagnesemia and Electrolyte Abnormalities [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described in Warnings and Precautions reflect exposure to ERBITUX in 1373 patients with SCCHN or CRC enrolled in clinical trials and treated at the recommended dosage for a median of 7 to 14 weeks [see Clinical Studies].
The most common adverse reactions in ERBITUX clinical trials (incidence ≥25%) include cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection.
Squamous Cell Carcinoma Of The Head And Neck (SCCHN)
In Combination with Radiation Therapy
The safety of ERBITUX in combination with radiation therapy compared to radiation therapy alone was evaluated in BONNER. The data described below reflect exposure to ERBITUX in 420 patients with locally or regionally advanced SCCHN. ERBITUX was administered at the recommended dosage (400 mg/m2 initial dose, followed by 250 mg/m2 weekly). Patients received a median of 8 infusions (range 1 to 11) [see Clinical Studies].
Table 2 provides the frequency and severity of adverse reactions in BONNER.
Table 2: Selected Adverse Reactions in ≥10% of Patients with Locoregionally Advanced SCCHN (BONNER)a
| Adverse Reaction | ERBITUX with Radiation (n=208) |
Radiation Therapy Alone (n=212) |
||
| Grades 1–4b |
Grades 3 and 4 |
Grades 1–4 |
Grades 3 and 4 |
|
| General | ||||
| Asthenia | 56 | 4 | 49 | 5 |
| Feverc | 29 | 1 | 13 | 1 |
| Headache | 19 | <1 | 8 | <1 |
| Chillsc | 16 | 0 | 5 | 0 |
| Infusion Reactiond | 15 | 3 | 2 | 0 |
| Infection | 13 | 1 | 9 | 1 |
| Gastrointestinal | ||||
| Nausea | 49 | 2 | 37 | 2 |
| Emesis | 29 | 2 | 23 | 4 |
| Diarrhea | 19 | 2 | 13 | 1 |
| Dyspepsia | 14 | 0 | 9 | 1 |
| Metabolism and Nutrition | ||||
| Weight Loss | 84 | 11 | 72 | 7 |
| Dehydration | 25 | 6 | 19 | 8 |
| Increased Alanine Transaminasee | 43 | 2 | 21 | 1 |
| Increased Aspartate Transaminasee | 38 | 1 | 24 | 1 |
| Increased Alkaline Phosphatasee | 33 | <1 | 24 | 0 |
| Respiratory | ||||
| Pharyngitis | 26 | 3 | 19 | 4 |
| Dermatologic | ||||
| Acneiform Rashf | 87 | 17 | 10 | 1 |
| Radiation Dermatitis | 86 | 23 | 90 | 18 |
| Application Site Reaction | 18 | 0 | 12 | 1 |
| Pruritus | 16 | 0 | 4 | 0 |
| a Adverse reactions occurring in ≥10% of patients in the ERBITUX combination arm and at a higher incidence (≥5%) compared to the radiation alone arm. b Adverse reactions were graded using the NCI CTC, version 2.0. c Includes cases also reported as infusion reaction. d Infusion reaction defined as any event described at any time during the clinical study as “allergic reaction” or “anaphylactoid reaction”, or any event occurring on the first day of dosing described as “allergic reaction”, “anaphylactoid reaction”, “fever”,“chills”, “chills and fever”, or “dyspnea”. e Based on laboratory measurements, not on reported adverse reactions, the number of subjects with tested samples varied from 205–206 for ERBITUX with Radiation arm; 209–210 for Radiation alone. f Acneiform rash defined as any event described as “acne”, “rash”, “maculopapular rash”, “pustular rash”, “dry skin”, or “exfoliative dermatitis”. |
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The overall incidence of late radiation toxicities (any grade) was higher for patients receiving ERBITUX in combination with radiation therapy compared with radiation therapy alone. The following sites were affected: salivary glands (65% versus 56%), larynx (52% versus 36%), subcutaneous tissue (49% versus 45%), mucous membrane (48% versus 39%), esophagus (44% versus 35%), skin (42% versus 33%). The incidence of Grade 3 or 4 late radiation toxicities was similar between the radiation therapy alone and the ERBITUX with radiation treatment groups.
In Combination with Platinum-based Therapy and Fluorouracil
The safety of a cetuximab product in combination with platinum-based therapy and fluorouracil or platinum-based therapy and fluorouracil alone was evaluated in EXTREME. The data described below reflect exposure to a cetuximab product in 434 patients with recurrent locoregional disease or metastatic SCCHN. Because ERBITUX provides approximately 22% higher exposure relative to the cetuximab product, the data provided below may underestimate the incidence and severity of adverse reactions anticipated with ERBITUX for this indication; however, the tolerability of the recommended dose is supported by safety data from additional studies of ERBITUX [see CLINICAL PHARMACOLOGY]. Cetuximab was administered intravenously at a dosage of 400 mg/m2 for the initial dose, followed by 250 mg/m2 weekly. Patients received a median of 17 infusions (range 1 to 89) [see Clinical Studies].
Table 3 provides the frequency and severity of adverse reactions in EXTREME.
Table 3: Selected Adverse Reactions in ≥10% of Patients with Recurrent Locoregional Disease or Metastatic SCCHN (EXTREME)a
| Adverse Reaction | Cetuximab with Platinum-based Therapy and fluorouracil (n=219) |
Platinum-based Therapy and fluorouracil Alone (n=215) |
||
| Grades 1–4b |
Grades 3 and 4 |
Grades 1–4 |
Grades 3 and 4 |
|
| Eye | ||||
| Conjunctivitis | 10 | 0 | 0 | 0 |
| Gastrointestinal | ||||
| Nausea | 54 | 4 | 47 | 4 |
| Diarrhea | 26 | 5 | 16 | 1 |
| General and Administration Site | ||||
| Pyrexia | 22 | 0 | 13 | 1 |
| Infusion Reactionc | 10 | 2 | <1 | 0 |
| Infections | ||||
| Infectiond | 44 | 11 | 27 | 8 |
| Metabolism and Nutrition | ||||
| Anorexia | 25 | 5 | 14 | 1 |
| Hypocalcemia | 12 | 4 | 5 | 1 |
| Hypokalemia | 12 | 7 | 7 | 5 |
| Hypomagnesemia | 11 | 5 | 5 | 1 |
| Dermatologic | ||||
| Acneiform Rashe | 70 | 9 | 2 | 0 |
| Rash | 28 | 5 | 2 | 0 |
| Acne | 22 | 2 | 0 | 0 |
| Dermatitis Acneiform | 15 | 2 | 0 | 0 |
| Dry Skin | 14 | 0 | <1 | 0 |
| Alopecia | 12 | 0 | 7 | 0 |
| a Adverse reactions occurring in ≥10% of patients in the cetuximab combination arm and at a higher incidence (≥5%) compared to the platinum-based therapy and fluorouracil alone arm. b Adverse reactions were graded using the NCI CTC, version 2.0. c Infusion reaction defined as “anaphylactic reaction”, “hypersensitivity”, “fever and/or chills”, “dyspnea”, or “pyrexia” on the first day of dosing. d Infection excludes sepsis-related events which are presented separately. e Acneiform rash defined as “acne”, “dermatitis acneiform”, “dry skin”, “exfoliative rash”, “rash”, “rash erythematous”, “rash macular”, “rash papular”, or “rash pustular”. Chemotherapy = cisplatin and fluorouracil or carboplatin and fluorouracil |
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For cardiac disorders, approximately 9% of patients in both treatment arms in EXTREME experienced a cardiac event. The majority of these events occurred in patients who received cisplatin and fluorouracil with or without cetuximab. Cardiac disorders were observed in 11% and 12% of patients who received cisplatin and fluorouracil with or without cetuximab, respectively, and 6% and 4% in patients who received carboplatin and fluorouracil with or without cetuximab, respectively. In both arms, the incidence of cardiovascular events was higher in the cisplatin and fluorouracil containing subgroup. Death attributed to cardiovascular events or sudden death was reported in 3% of the patients in the cetuximab with platinum-based therapy and fluorouracil arm and in 2% of the patients in the platinum-based therapy and fluorouracil alone arm.
K-Ras Wild-Type, EGFR-Expressing, Metastatic Colorectal Cancer (mCRC)
In Combination with FOLFIRI
The safety of a cetuximab product in combination with FOLFIRI or FOLFIRI alone was evaluated in CRYSTAL. The data described below reflect exposure to a cetuximab product in 667 patients with K-Ras wild-type, EGFR-expressing, mCRC. ERBITUX provides approximately 22% higher exposure compared to this product; however, the safety data from CRYSTAL is consistent in incidence and severity of adverse reactions with those seen for ERBITUX in this indication. Cetuximab was administered intravenously at a dosage of 400 mg/m2 initial dose, followed by 250 mg/m2 weekly. Patients received a median of 24 infusions (range 1 to 224) [see Clinical Studies].
Serious adverse reactions included pulmonary embolism, which was reported in 4.4% of patients treated with cetuximab with FOLFIRI as compared to 3.4% of patients treated with FOLFIRI alone.
Table 4 provides the frequency and severity of adverse reactions in CRYSTAL.
Table 4: Selected Adverse Reactions in ≥10% of Patients with K-Ras Wild-type and EGFR-expressing, Metastatic Colorectal Cancer (CRYSTAL)a
| Adverse Reaction | Cetuximab with FOLFIRI (n=317) |
FOLFIRI Alone (n=350) |
||
| Grades 1–4b |
Grades 3 and 4 |
Grades 1–4 |
Grades 3 and 4 |
|
| Hematologic | ||||
| Neutropenia | 49 | 31 | 42 | 24 |
| Eye | ||||
| Conjunctivitis | 18 | <1 | 3 | 0 |
| Gastrointestinal | ||||
| Diarrhea | 66 | 16 | 60 | 10 |
| Stomatitis | 31 | 3 | 19 | 1 |
| Dyspepsia | 16 | 0 | 9 | 0 |
| General and Administration Site | ||||
| Pyrexia | 26 | 1 | 14 | 1 |
| Weight Decreased | 15 | 1 | 9 | 1 |
| Infusion Reactionc | 14 | 2 | <1 | 0 |
| Infections | ||||
| Paronychia | 20 | 4 | <1 | 0 |
| Metabolism and Nutrition | ||||
| Anorexia | 30 | 3 | 23 | 2 |
| Dermatologic | ||||
| Acne-like Rashd | 86 | 18 | 13 | <1 |
| Rash | 44 | 9 | 4 | 0 |
| Dermatitis Acneiform | 26 | 5 | <1 | 0 |
| Dry Skin | 22 | 0 | 4 | 0 |
| Acne | 14 | 2 | 0 | 0 |
| Pruritus | 14 | 0 | 3 | 0 |
| Palmar-plantar Erythrodysesthesia Syndrome | 19 | 4 | 4 | <1 |
| Skin Fissures | 19 | 2 | 1 | 0 |
| a Adverse reactions occurring in ≥10% of patients in the cetuximab combination arm and at a higher incidence (≥5%) compared to the FOLFIRI alone arm. b Adverse reactions were graded using the NCI CTC, version 2.0. c Infusion reaction defined as any event meeting the medical concepts of allergy/anaphylaxis at any time during the clinical study or any event occurring on the first day of dosing and meeting the medical concepts of dyspnea and fever or by the following events: “acute myocardial infarction”, “angina pectoris”, “angioedema”, “autonomic seizure”, “blood pressure abnormal”, “blood pressure decreased”, “blood pressure increased”, “cardiac failure”, “cardiopulmonary failure”, “cardiovascular insufficiency”, “clonus”, “convulsion”, “coronary no-reflow phenomenon”, “epilepsy”, “hypertension”, “hypertensive crisis”, “hypertensive emergency”, “hypotension”, “infusion related reaction”, “loss of consciousness”, “myocardial infarction”, “myocardial ischemia”, “prinzmetal angina”, “shock”, “sudden death”, “syncope”, or “systolic hypertension”. d Acne-like rash defined by the following events: “acne”, “acne pustular”, “butterfly rash”, “dermatitis acneiform”, “drug rash with eosinophilia and systemic symptoms”, “dry skin”, “erythema”, “exfoliative rash”, “folliculitis”, “genital rash”, “mucocutaneous rash”, “pruritus”, “rash”, “rash erythematous”, “rash follicular”, “rash generalized”, “rash macular”, “rash maculopapular”, “rash maculovesicular”, “rash morbilliform”, “rash papular”, “rash papulosquamous”, “rash pruritic”, “rash pustular”, “rash rubelliform”, “rash scarlatiniform”, “rash vesicular”, “skin exfoliation”, “skin hyperpigmentation”, “skin plaque”, “telangiectasia”, or “xerosis”. |
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As Single-Agent
The safety of ERBITUX with best supportive care (BSC) or BSC alone was evaluated in Study CA225-025. The data described below reflect exposure to ERBITUX in 242 patients with K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer (mCRC) [see WARNINGS AND PRECAUTIONS]. ERBITUX was administered intravenously at the recommended dosage (400 mg/m2 initial dose, followed by 250 mg/m2 weekly). Patients received a median of 17 infusions (range 1 to 51) [see Clinical Studies].
Table 5 provides the frequency and severity of adverse reactions in Study CA225-025.
Table 5: Selected Adverse Reactions in ≥10% of Patients with K-Ras Wild-type, EGFR-expressing, Metastatic Colorectal Cancer Treated with Single-Agent ERBITUX (Study CA225-025)a
| Adverse Reaction | ERBITUX with BSC (n=118) |
BSC alone (n=124) |
||
| Grades 1–4b |
Grades 3 and 4 |
Grades 1–4 |
Grades 3 and 4 |
|
| Nail Changes | 31 | 0 | 4 | 0 |
| General | ||||
| Fatigue | 91 | 31 | 79 | 29 |
| Fever | 25 | 3 | 16 | 0 |
| Infusion Reactionsc | 18 | 3 | 0 | 0 |
| Rigors, Chills | 16 | 1 | 3 | 0 |
| Pain | ||||
| Pain-Other | 59 | 18 | 37 | 10 |
| Headache | 38 | 2 | 11 | 0 |
| Bone Pain | 15 | 4 | 8 | 2 |
| Pulmonary | ||||
| Dyspnea | 49 | 16 | 44 | 13 |
| Cough | 30 | 2 | 19 | 2 |
| Gastrointestinal | ||||
| Nausea | 64 | 6 | 50 | 6 |
| Constipation | 53 | 3 | 38 | 3 |
| Diarrhea | 42 | 2 | 23 | 2 |
| Vomiting | 40 | 5 | 26 | 5 |
| Stomatitis | 32 | 1 | 10 | 0 |
| Other | 22 | 12 | 16 | 5 |
| Dehydration | 13 | 5 | 3 | 0 |
| Mouth Dryness | 12 | 0 | 6 | 0 |
| Taste Disturbance | 10 | 0 | 5 | 0 |
| Infection | ||||
| Infection without neutropenia | 38 | 11 | 19 | 5 |
| Musculoskeletal | ||||
| Arthralgia | 14 | 3 | 6 | 0 |
| Neurological | ||||
| Neuropathy-sensory | 45 | 1 | 38 | 2 |
| Insomnia | 27 | 0 | 13 | 0 |
| Confusion | 18 | 6 | 10 | 2 |
| Anxiety | 14 | 1 | 5 | 1 |
| Depression | 14 | 0 | 5 | 0 |
| a Adverse reactions occurring in ≥10% of patients in the ERBITUX with BSC arm and at a higher incidence (≥5%) compared to the BSC alone arm. b Adverse reactions were graded using the NCI CTC, version 2.0. c Infusion reaction defined as any event (chills, rigors, dyspnea, tachycardia, bronchospasm, chest tightness, swelling, urticaria, hypotension, flushing, rash, hypertension, nausea, angioedema, pain, sweating, tremors, shaking, drug fever, or other hypersensitivity reaction) recorded by the investigator as infusion-related. |
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In Combination with Irinotecan
ERBITUX at the recommended dosage was administered in combination with irinotecan in 354 patients with EGFR-expressing recurrent mCRC in Study CP02-9923 and BOND.
The most common adverse reactions were acneiform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most common Grades 3–4 adverse reactions included diarrhea (22%), leukopenia (17%), asthenia/malaise (16%), and acneiform rash (14%).
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to cetuximab in the studies below with the incidence of antibodies to cetuximab in other studies or to other products may be misleading.
An ELISA methodology was used to characterize the incidence of anti-cetuximab antibodies. The incidence of anticetuximab binding antibodies in 105 patients (from studies I4E-MC-JXBA, I4E-MC-JXBB, and I4E-MC-JXBD) with at least one post-baseline blood sample (≥4 weeks post first ERBITUX administration) was <5%.
Postmarketing Experience
The following adverse reactions have been identified during post approval use of ERBITUX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Neurologic: Aseptic meningitis
- Gastrointestinal: Mucosal inflammation
- Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, life-threatening and fatal bullous mucocutaneous disease
DRUG INTERACTIONS
No Information Provided
Read the entire FDA prescribing information for Erbitux (Cetuximab)
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