ERBITUX PI PDF

treated with Erbitux and radiation therapy and in 3% of patients Limitation of Use: Erbitux is not indicated for treatment of K-Ras mutation- positive colorectal. Each mL of solution for infusion contains 5 mg cetuximab. Erbitux is indicated for the treatment of patients with squamous cell cancer of the head and neck. Erbitux is indicated for the treatment of patients with squamous cell cancer of the head and neck All sections. PI reformatted.

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Medically reviewed on Jun 1, Erbitux can cause serious and fatal infusion reactions [see Warnings and Precautions 5. Immediately interrupt and permanently discontinue Erbitux for serious infusion reactions [see Ebritux and Administration 2.

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. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux administration [see Warnings and Precautions 5.

Erbitux is not indicated for treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests erbiutx unknown [see Warnings and Precautions 5. In combination with radiation therapy or platinum-based therapy and fluorouracil. Also confirm the erbituz of a Ras mutation prior to initiation of treatment with Erbitux.

Premedicate with a histamine-1 H 1 receptor antagonist intravenously 30—60 minutes prior to the first dose or subsequent doses as deemed necessary [see Warnings and Precautions 5. Reduce, delay, or discontinue Erbitux to manage adverse reactions as described in Table 1. Erbitux can cause serious and fatal infusion reactions. Infusion reactions of any grade occurred in 8.

Severe Grades 3 and 4 infusion reactions occurred in 2. Infusion reactions may occur during or several hours following completion of the infusion. Premedicate with a histamine-1 H 1 receptor antagonist as recommended [see Dosage and Administration 2. Monitor patients for at least 1 hour following each Erbitux infusion, in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis.

In patients requiring treatment for infusion reactions, monitor for more than 1 hour to confirm resolution of the reaction. Interrupt the infusion and upon recovery, resume the infusion at a slower rate or permanently discontinue Erbitux based on severity [see Dosage and Administration 2.

Erbitux can cause cardiopulmonary arrest. Three patients with prior history of coronary artery disease died at home, with myocardial infarction as the presumed cause of death. One of these patients had arrhythmia and one had congestive heart failure.

Death occurred 27, 32, and 43 days after the last dose of Erbitux. One patient with no prior history of coronary artery disease died one day after the last dose of Erbitux. Carefully consider use of Erbitux with radiation therapy or platinum-based therapy with fluorouracil in patients with SCCHN with a history of coronary artery disease, congestive heart failure, or arrhythmias. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux [see Warnings and Precautions 5.

Erbitux can cause interstitial lung disease ILD. Monitor patients for signs and symptoms of pulmonary toxicity. Interrupt or permanently discontinue Erbitux for acute onset or worsening of pulmonary symptoms. Erbitux can cause dermatologic toxicities, including acneiform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae for example, S. Severe Grades 3 or 4 acneiform rash occurred in 9.

Acneiform rash usually developed within the first two weeks of therapy; the rash lasted more than 28 days after stopping Erbitux in most patients. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing, has been observed in patients who received Erbitux.

It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects e. Monitor patients receiving Erbitux for dermatologic toxicities and infectious sequelae. Instruct patients to limit sun exposure erbitkx Erbitux therapy.

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Withhold, reduce dose or erbiux discontinue Erbitux based on severity of acneiform rash or mucocutaneous disease [see Dosage and Administration 2. The addition of Erbitux resulted in an increase in the incidence of Grade 3 and 4 mucositis, radiation recall erbirux, acneiform rash, cardiac events, and electrolyte disturbances compared to radiation ergitux cisplatin alone.

The main efficacy outcome of the study was progression-free survival PFS.

The addition of Erbitux to radiation and cisplatin did not improve PFS. Erbitux can cause hypomagnesemia. No patient experienced Grade 3 or 4 hypomagnesemia [see Adverse Reactions 6. Hypomagnesemia and accompanying electrolyte abnormalities can occur days to months after initiating Erbitux.

Monitor patients weekly during treatment for erbityx, hypocalcemia, and hypokalemia, and for at least 8 weeks following the completion of Erbitux. Replete electrolytes as necessary. Retrospective subset analyses of Ras-mutant and wild-type populations across several randomized clinical trials, including CRYSTAL, were conducted to investigate the role of Ras mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies. Use of cetuximab in patients with Ras mutations resulted in no clinical benefit with treatment related toxicity.

Confirm Ras mutation status in tumor specimens prior to initiating Erbitux [see Indications and Usage 1. There are no available data for Erbitux exposure in pregnant women. In an animal reproduction study, intravenous administration of cetuximab once weekly to pregnant cynomolgus monkeys during the period of organogenesis resulted in an increased incidence of embryolethality and abortion.

Disruption or depletion of EGFR in animal models results in impairment of embryo-fetal development including effects on placental, lung, cardiac, skin, and neural development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Erbitux and for 2 months after the last dose of Erbitux [see Use in Specific Populations 8.

The following adverse reactions are discussed in greater detail in other sections of the label:. 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.

Patients received a median of 8 infusions range 1 to 11 [see Clinical Studies 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.

erbbitux The following sites were affected: 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.

Patients received a median of eerbitux infusions range 1 to 89 [see Clinical Studies The majority of these events occurred in patients who received cisplatin and fluorouracil with or without cetuximab. In erbltux arms, the incidence of cardiovascular events was higher in the cisplatin and fluorouracil containing subgroup. Patients received a median of 24 infusions range 1 to [see Clinical Studies Table 5 provides the frequency and severity of adverse reactions in Study Ervitux 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.

Cetuximab in the management of colorectal cancer

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. The following adverse reactions have been identified during post approval use of Erbitux. Because these reactions are erbituxx voluntarily from a population of uncertain size, it is not always possible pj reliably estimate their frequency or establish a causal relationship to drug exposure. Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology Disruption or depletion of EGFR in animal models results in impairment of embryo-fetal development including effects on placental, lung, cardiac, skin, and neural development see Data.

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Human IgG is known to cross the placental barrier; therefore, cetuximab may be transmitted from the mother to the developing fetus. Pregnant cynomolgus monkeys were administered cetuximab intravenously once weekly during the period of organogenesis gestation day [GD] at dose levels 0.

Cetuximab – DrugBank

Cetuximab was detected in the amniotic fluid and in ebritux serum of embryos from treated dams on GD While no fetal malformations occurred in offspring, there was an increased incidence of erbiyux and abortions at doses approximately 1 to 4 times the recommended dose of Erbitux based pj BSA. Reduction or elimination of embryo-fetal or maternal EGFR signaling can prevent implantation, can cause embryo-fetal loss during various stages of gestation through effects on placental developmentand can cause developmental anomalies and early death in surviving fetuses.

There is no information regarding the presence of Erbitux in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG antibodies can be excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants from Erbitux, advise women not to breastfeed during treatment with Erbitux and for 2 months after the last dose of Erbitux. Verify pregnancy status in females of reproductive potential prior to initiating Erbitux [see Use in Specific Population 8.

Based on its mechanism of action, Erbitux can cause harm to the fetus when administered to a pregnant woman [see Use in Specific Populations 8. Based on animal studies, Ppi may impair fertility in females of reproductive potential [see Nonclinical Toxicology The safety and effectiveness of Erbitux in pediatric patients have not been established.

The pharmacokinetics of cetuximab, in combination with irinotecan, were evaluated in ebitux patients with refractory solid tumors in an open-label, single-arm, dose-finding study. No new safety signals were identified in pediatric patients.

Cetuximab in the management of colorectal cancer

No overall differences in safety or efficacy were observed between these patients and younger patients. Clinical studies of Erbitux conducted in patients with head and neck cancer did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Cetuximab erbithx an epidermal growth factor receptor EGFR antagonist.

Cetuximab is produced in mammalian murine myeloma cell culture. Erbitux cetuximab injection for intravenous use, is a sterile, preservative-free, clear, colorless solution, which may contain a small amount of visible, white, amorphous cetuximab particulates in a single-dose vial.

The EGFR is constitutively expressed in many normal epithelial tissues, including the skin and hair follicle. Expression of EGFR is also detected in many human cancers including those of the head and neck, colon, and rectum.

Cetuximab binds specifically to the EGFR on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor EGF and other ligands, such as transforming growth factor-alpha. In vitro assays and in vivo animal studies have shown that binding of cetuximab to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of po growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor erbjtux.

Signal egbitux through the EGFR results in activation of wild-type Ras proteins, but in cells with activating Ras somatic mutations, the resulting mutant Erbituux proteins are continuously active regardless of EGFR regulation. In vitrocetuximab can mediate antibody-dependent cellular cytotoxicity ADCC against certain human tumor types.

In vitro assays and in vivo animal studies have shown that cetuximab inhibits the growth and survival of tumor cells that express the EGFR.