HIGHLIGHTS OF PRESCRIBING INFORMATION ERBITUXsafely …

1 1. HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------DOSAGE AND ADMINISTRATION---------------------- These HIGHLIGHTS do not include all the INFORMATION needed to use Premedicate with an H1 receptor antagonist. ( ). erbitux safely and effectively. See full PRESCRIBING INFORMATION 2. for erbitux . Administer 400 mg/m initial dose as a 120-minute intravenous 2.. erbitux (cetuximab) injection, for intravenous use infusion followed by 250 mg/m weekly infused over 60 minutes. ( , , ). Initial Approval: 2004. Initiate erbitux one week prior to initiation of radiation therapy. WARNING: INFUSION REACTIONS and CARDIOPULMONARY Complete erbitux administration 1 hour prior to irinotecan, ARREST platinum-based therapy with fluorouracil or FOLFIRI.

2 ( , ). See full PRESCRIBING INFORMATION for complete boxed warning. erbitux can cause serious and fatal infusion reactions. ----------------------DOSAGE FORMS AND STRENGTHS-------------------- ( , 6) Immediately interrupt and permanently discontinue Injection: 100 mg/50 mL (2 mg/mL) or 200 mg/100 mL (2 mg/mL). erbitux for serious infusion reactions. ( ) in a single- dose vial. (3). Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and ------------------------------CONTRAINDI CATIONS------------------------------- neck receiving erbitux with radiation therapy or with a None. (4). cetuximab product with platinum-based therapy and fluorouracil.

3 Monitor serum electrolytes, including serum ----------------------WARNINGS AND PRECAUTIONS------------------------- magnesium, potassium, and calcium, during and after Infusion Reactions: Monitor patients following infusion. erbitux administration. ( , ). Immediately stop and permanently discontinue erbitux for serious infusion reactions. ( , ). ---------------------------RECENT MAJOR CHANGES--------------------------- Cardiopulmonary Arrest: Monitor serum electrolytes during and Dosage and Administration, after erbitux . ( , ). Dosage Modifications for Adverse Reactions ( ) 6/2018. Pulmonary Toxicity: Interrupt or permanently discontinue for acute Warnings and Precautions, Infusion Reactions ( ) 6/2018 onset or worsening of pulmonary symptoms.

4 ( , ). Warnings and Precautions, Embryo-Fetal Toxicity ( ) 5/2018 Dermatologic Toxicity: Monitor for dermatologic toxicities or infectious sequelae. Limit sun exposure. ( , ). ---------------------------INDICATIONS AND USAGE---------------------------- . Hypomagnesemia and Accompanying Electrolyte Abnormalities: erbitux is an epidermal growth factor receptor (EGFR) antagonist Monitor during treatment and for at least 8 weeks following the indicated for treatment of: completion. Replete electrolytes as necessary. ( ). Head and Neck Cancer Increased tumor progression, increased mortality, or lack of benefit Locally or regionally advanced squamous cell carcinoma of the observed in patients with Ras-mutant mCRC.

5 ( ). head and neck in combination with radiation therapy. ( , ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of Recurrent locoregional disease or metastatic squamous cell potential risk to the fetus and to use effective contraception. ( , carcinoma of the head and neck in combination with platinum- , ). based therapy with fluorouracil. ( , ). Recurrent or metastatic squamous cell carcinoma of the head and -------------------------------ADVERSE REACTIONS------------------------------ neck progressing after platinum-based therapy. ( , ) The most common adverse reactions (incidence 25%) are: cutaneous adverse reactions (including rash, pruritus, and nail changes), Colorectal Cancer headache, diarrhea, and infection.

6 (6). K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800- in combination with FOLFIRI for first-line treatment, FDA-1088 or in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy, ------------------------USE IN SPECIFIC POPULATIONS----------------------- as a single agent in patients who have failed oxaliplatin- and Lactation: Advise not to breastfeed. ( ). irinotecan-based chemotherapy or who are intolerant to irinotecan. ( , , , ) See 17 for PATIENT COUNSELING INFORMATION .

7 Limitations of Use: erbitux is not indicated for treatment of Ras- Revised: 4/2019. mutant colorectal cancer or when the results of the Ras mutation tests are unknown. ( ). FULL PRESCRIBING INFORMATION : CONTENTS*. WARNING: INFUSION REACTIONS and CARDIOPULMONARY 5 WARNINGS AND PRECAUTIONS. ARREST Infusion Reactions 1 INDICATIONS AND USAGE Cardiopulmonary Arrest Squamous Cell Carcinoma of the Head and Neck (SCCHN) Pulmonary Toxicity K-Ras Wild-type, EGFR-expressing Colorectal Cancer Dermatologic Toxicity (CRC) Risks Associated with Use in Combination with radiation 2 DOSAGE AND ADMINISTRATION and Cisplatin Recommended Dosage for Squamous Cell Carcinoma of Hypomagnesemia and Accompanying Electrolyte the Head and Neck (SCCHN) Abnormalities Recommended Dosage for Colorectal Cancer (CRC) Increased Tumor Progression, Increased Mortality, or Lack Premedication of Benefit in Patients with Ras-Mutant mCRC.

8 Dosage Modifications for Adverse Reactions Embryo-Fetal Toxicity Preparation for Administration 6 ADVERSE REACTIONS. 3 DOSAGE FORMS AND STRENGTHS Clinical Trials Experience Immunogenicity 4 CONTRAINDICATIONS. 2. Postmarketing Experience 13 NONCLINICAL TOXICOLOGY. 8 USE IN SPECIFIC POPULATIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy 14 CLINICAL STUDIES. Lactation Squamous Cell Carcinoma of the Head and Neck (SCCHN). Females and Males of Reproductive Potential K-Ras Wild-type, EGFR-expressing, Metastatic Colorectal Pediatric Use Cancer (CRC). Geriatric Use 16 HOW SUPPLIED/STORAGE AND HANDLING. 11 DESCRIPTION 17 PATIENT COUNSELING INFORMATION .

9 12 CLINICAL PHARMACOLOGY * Sections or subsections omitted from the full PRESCRIBING INFORMATION Mechanism of Action are not listed. Pharmacokinetics FULL PRESCRIBING INFORMATION . WARNING: INFUSION REACTIONS and CARDIOPULMONARY ARREST. Infusion Reactions: erbitux can cause serious and fatal infusion reactions [see Warnings and Precautions ( ), Adverse Reactions (6)]. Immediately interrupt and permanently discontinue erbitux for serious infusion reactions [see Dosage and Administration ( )]. Cardiopulmonary Arrest: Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and neck receiving erbitux with radiation therapy or a cetuximab product with platinum-based therapy and fluorouracil.

10 Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after erbitux administration [see Warnings and Precautions ( , )]. 1 INDICATIONS AND USAGE. 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 (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.