Cetuximab


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV Metastatic colorectal cancer Patients with EGFR-expressing, RAS wild-type cases: As monotherapy in those who failed oxaliplatin- and irinotecan-based treatment and who are intolerant to irinotecan, or as 1st-line option in combination with FOLFOX or FOLFIRI, or in combination with irinotecan in patients refractory to irinotecan-based chemotherapy: Initial: 400 mg/m2 loading dose. Maintenance dose: 250 mg/m2 once weekly, continue until disease progression or unacceptable toxicity. Complete administration 1 hour prior to concomitantly used chemotherapeutic agents. Locally advanced squamous cell carcinoma of the head and neck In combination with radiation therapy: Initial: 400 mg/m2 loading dose, given 1 week prior to radiation therapy. Maintenance dose: 250 mg/m2 once weekly, continued until the end of radiation therapy period. Recurrent squamous cell carcinoma of the head and neck; Metastatic squamous cell carcinoma of the head and neck In combination with platinum-based chemotherapy, or as monotherapy in patients whom prior platinum-based therapy failed: Initial: 400 mg/m2 loading dose. Maintenance dose: 250 mg/m2 once weekly, continue until disease progression or unacceptable toxicity. All initial loading doses are given via slow IV infusion over 2 hours with max infusion rate of 5 mg/min, and all subsequent maintenance doses are given via IV infusion over 1 hour with max infusion rate of 10 mg/min. Refer to detailed product guideline for administration and handling.
Dosage Details
Intravenous
Metastatic colorectal cancer
Adult: Patients with EGFR-expressing, RAS wild-type cases: As monotherapy in those who failed oxaliplatin- and irinotecan-based treatment and who are intolerant to irinotecan, or as 1st-line option in combination with FOLFOX (fluorouracil, folinic acid, oxaliplatin infusion) or FOLFIRI (fluorouracil, folinic acid, irinotecan), or in combination with irinotecan in patients refractory to irinotecan-based chemotherapy: Initially, 400 mg/m2 loading dose via slow infusion over 2 hours, with max infusion rate of 5 mg/minute. Maintenance dose: 250 mg/m2 once weekly via infusion over 1 hour, with max infusion rate of 10 mg/minute. Continue until disease progression or unacceptable toxicity. Refer to detailed product guideline for administration and handling.

Intravenous
Locally advanced squamous cell carcinoma of the head and neck
Adult: In combination with radiation therapy: Initially, 400 mg/m2 loading dose via slow infusion over 2 hours, with max infusion rate of 5 mg/minute, given 1 week prior to radiation therapy. Maintenance dose: 250 mg/m2 once weekly via infusion over 1 hour with max infusion rate of 10 mg/minute, continued until the end of radiation therapy period. Refer to detailed product guideline for administration and handling.

Intravenous
Metastatic squamous cell carcinoma of the head and neck, Recurrent squamous cell carcinoma of the head and neck
Adult: In combination with platinum-based chemotherapy, or as monotherapy in patients whom prior platinum-based therapy failed: Initially, 400 mg/m2 loading dose via slow infusion over 2 hours, with max infusion rate of 5 mg/minute. Maintenance dose: 250 mg/m2 once weekly via infusion over 1 hour, with max infusion rate of 10 mg/minute. Continue until disease progression or unacceptable toxicity. Refer to detailed product guideline for administration and handling.
Special Patient Group
Pharmacogenomics:

Activating mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) were identified in which chronically activated form of RAS is dissociated from EGFR and contributes to cellular proliferation and independent EGFR occupation. These mutations are associated with anti-EGFR treatment-resistant phenotypes and may affect the pharmacodynamics of cetuximab. The most common variants observed in colorectal cancer patients appeared to be glycine to aspartate at codon 12 (approx 33-38%) or codon 13 (approx 12-21%), and glycine to valine at codon 12 (approx 22-31%).

Based from research, colorectal cancer patients with wild-type KRAS who received cetuximab experienced a significant improvement in overall survival and progression-free survival. Cetuximab should not be given in individuals with unknown RAS mutations, or in patients with mutations in codons 12 and 13 in KRAS exon 2 as it is predicted to have a lack of response to anti-EGFR monoclonal antibodies.

EMA and FDA drug labels for cetuximab recommend performing approved and validated testing methods for the evidence of wild-type RAS (KRAS and NRAS) status prior to initiating treatment in metastatic colorectal cancer patients.
Contraindications
Known severe (grade 3 or 4) hypersensitivity reactions to cetuximab. Patients with mutant RAS metastatic colorectal cancer (mCRC) or those with unknown RAS mCRC status (in combination with oxaliplatin-containing chemotherapy). Lactation. Contraindications of concomitant chemotherapeutic agents or radiation therapy should be considered.
Special Precautions
Patients with history of coronary artery disease, heart failure, and arrhythmias; history of tick bites, allergy to red meat, or positive test results for IgE antibodies against α-1-3-galactose; pre-existing cardio-pulmonary disease; history of keratitis, ulcerative keratitis or dry eyes; chronic infections, history of recurring infections or underlying conditions predisposing to infections. Not indicated for the treatment of squamous cell carcinoma of the head and neck in combination with radiation and cisplatin. Pregnancy.
Adverse Reactions
Significant: Severe neutropenia; electrolyte abnormalities (e.g. hypomagnesaemia, hypokalaemia, hypocalcaemia), dermatologic toxicities (e.g. acneiform rash, dry skin, fissures, hypertrichosis, paronychial inflammation, skin infection), ocular toxicities (e.g. blepharitis, conjunctivitis, keratitis, ulcerative keratitis with decreased visual acuity), mild to moderate infusion-related reactions (e.g. fever, chills, dizziness, dyspnoea).
Gastrointestinal disorders: Diarrhoea, nausea, vomiting.
General disorders and admin site conditions: Mucositis, fatigue, asthenia, inj site reactions.
Infections and infestations: Infection.
Investigations: Weight decreased, increased ALT/AST and alkaline phosphatase.
Metabolism and nutrition disorders: Dehydration, anorexia.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Pulmonary embolism, pharyngitis.
Skin and subcutaneous tissue disorders: Pruritus, desquamation, radiation dermatitis. Rarely, Stevens-Johnson disease, toxic epidermal necrolysis.
Vascular disorders: DVT.
Potentially Fatal: Bullous mucocutaneous disease, staphylococcal scalded skin syndrome, necrotising fasciitis, sepsis, interstitial lung disease (ILD), severe infusion-related reactions.
IV/Parenteral: C
Patient Counseling Information
Exposure to sunlight may worsen skin reactions. Limit your sun exposure, use sunscreen and protective clothing while outdoors.
MonitoringParameters
Determine RAS mutation status using validated test methods for detection of KRAS and NRAS (exons 2, 3 and 4) mutations prior to mCRC treatment initiation. Perform pregnancy test before starting treatment. Monitor serum Mg, Ca, and K weekly during therapy and for at least 8 weeks after treatment completion; signs and symptoms of dermatologic and pulmonary toxicities. Closely monitor patient’s vital signs during and for at least 1 hour after the end of infusion.
Drug Interactions
Increased frequency of severe leucopenia or neutropenia when combined with platinum-based chemotherapy. Increased frequency of cardiac ischaemia including MI, CHF, and hand-foot syndrome when combined with fluoropyrimidines. May increase frequency of severe diarrhoea when concurrently used with capecitabine and oxaliplatin. Increased risk of secondary transmission of infection with live vaccines.
Potentially Fatal: Increased incidence of adverse effects in combination with radiation and cisplatin.
Action
Description: Cetuximab is a recombinant human/mouse chimeric monoclonal IgG1 antibody that specifically binds to epidermal growth factor receptor (EGFR), and competitively inhibits the binding of EGFR and other ligands. This blocks phosphorylation and activation of receptor-associated kinases, thereby inhibiting cell growth, inducing apoptosis, and decreasing production of matrix metalloproteinase and vascular endothelial growth factor. EGFR signal transduction leads to rat sarcoma (RAS) wild-type activation, including its KRAS and NRAS subtypes; however, cells with RAS mutations appear to be unaffected by EGFR inhibition.
Pharmacokinetics:
Distribution: Volume of distribution: Approx 2-3 L/m2.
Excretion: Elimination half-life: Approx 112 hours.
Storage
Store between 2-8°C.
ATC Classification
L01XC06 - cetuximab ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
References
Annotation of EMA Label for Cetuximab and EGFR, KRAS, NRAS. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 16/12/2019.

Annotation of FDA Label for Cetuximab and EGFR, KRAS, NRAS. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 16/12/2019.

Anon. Cetuximab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 16/12/2019.

Anon. V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 16/12/2019.

Buckingham R (ed). Cetuximab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/12/2019.

Erbitux Solution (ImClone LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 16/12/2019.

Disclaimer: This information is independently developed by MIMS based on Cetuximab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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