Cetuximab Drugbank ID : DB00002 Protein Chemical formula : C6484H10042N1732O2023S36 Protein Average wt. : 145781.6 Half life : Approximately : 114 hrs

Pharmacodynamics : Description : Indication : Erbitux is a targeted therapy.  It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). Indication : For treatment of EGFR-expressing metastatic colorectal cancer in patients who are refractory to other irinotecan-based chemotherapy regimens. Cetuximab is also indicated for treatment of squamous cell carcinoma of the head and neck in conjucntion with radiation therapy. Pharmacodynamics : Used in the treatment of colorectal cancer, cetuximab binds specifically to the epidermal growth factor receptor (EGFr, HER1, c-ErbB-1) on both normal and tumor cells. EGFr is over-expressed in many colorectal cancers. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor–alpha. Binding of cetuximab to the EGFr blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased matrix metalloproteinase secretion and reduced vascular endothelial growth factor production.

Mechanism of action : Toxicity : Cetuximab binds to the epidermal growth factor receptor (EGFr) on both normal and tumor cells. EGFr is over-expressed in many colorectal cancers. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and TGF alpha, thereby reducing their effects on cell growth and metastatic spread. Toxicity : Single doses of cetuximab higher than 500 mg/m^2 have not been tested. There is no experience with overdosage in human clinical trials.

Targets : Affected organisms : Epidermal growth factor receptor 2)Low affinity immunoglobulin gamma Fc region receptor III-B, 3) Complement C1r subcomponent, 4) Complement C1q subcomponent subunit A, 5) Complement C1q subcomponent subunit B, 6) Complement C1q subcomponent subunit C, 7) Low affinity immunoglobulin gamma Fc region receptor III-A, 8) Complement C1s subcomponent, 9) High affinity immunoglobulin gamma Fc receptor I, 10) Low affinity immunoglobulin gamma Fc region receptor II-a, 11) Low affinity immunoglobulin gamma Fc region receptor II-b, 12) Low affinity immunoglobulin gamma Fc region receptor II-c Affected organisms : Humans and other mammals

Categories : Patents : Sequence : Antineoplastic Agents Country Patent Number Approved Expires (estimated) Canada 1340417 1999-03-02 2016-03-02 Sequence : Cetuximab heavy chain = QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK and Cetuximab light chain = DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGA

Brands : Erbitux Company : ImClone Systems Inc Description : Erbitux is a targeted therapy.  It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). Used for/Prescribed for : used to treat metastatic colorectal cancer (cancer spread beyond the colon or rectum) that over-expresses the epidermal growth factor receptor (EGFR) and approved for the the treatment of squamous cell carcinoma of the head and neck. Formulation : formulated in a solution with no preservatives, which contains 8.48 mg/mL sodium chloride, 1.88 mg/mL sodium phosphate dibasic heptahydrate, 0.41 mg/mL sodium phosphate monobasic monohydrate, and Water for Injection, USP Form : sterile, clear, colorless liquid of pH 7.0 to 7.4, which may contain a small amount of easily visible, white, amorphous cetuximab particulates Route of administration : Intravenous Infusion

Dosage : usually given once every week for 6 to 7 weeks Dosage : usually given once every week for 6 to 7 weeks. And supplied at a concentration of 2 mg/mL in either 100 mg (50 mL) or 200 mg (100 mL), single-use vials. Contraindication : allergic Side effects : Rash (Acne like), Generalized weakness, malaise, Fever, Low magnesium level are commom (occurring in greater than 30%) for patients taking Erbitux. And less coomon side effects (occurring in about 10-29%) of patients receiving Erbitux are; Nausea and vomiting, Diarrhea, Constipation, Poor appetite, Headache, Abdominal pain, Nail disorder - inflammation of the skin surrounding a fingernail or toenail, Mouth sores, Swelling, Difficulty sleeping, Itching, Low red blood cell count (Anemia), Cough Drug interaction : 19 drugs (55 brand and generic names) interact with erbitux in which 1 Major and 18 moderate interction.

References : http://chemocare. com/chemotherapy/drug-info/erbitux