Erbitux

Erbitux Uses, Dosage, Side Effects, Food Interaction and all others data.

Erbitux is a recombinant human/mouse chimeric monoclonal antibody. It binds specifically to the epidermal growth factor receptor (EGFR), thus competitively inhibiting the binding of epidermal growth factor (EGF) and other ligands. This blocks phosphorylation and activation of receptor-associated kinases, thus inhibiting cell growth, inducing apoptosis and decreases matrix metalloproteinase and vascular EGF production.

Erbitux is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells with high specificity and higher affinity than epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are natural ligands of EGFR. Erbitux works by inhibiting the growth and survival of EGFR-positive tumours. In vitro, it promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. On the contrary, cetuximab does not exert its anti-tumour effects on human tumour xenografts lacking EGFR expression.

Erbitux potentiates the cytotoxic effects of chemotherapeutics and radiation therapy when used in combination. In human tumour xenograft models in mice, cetuximab and irinotecan synergistically inhibited the growth of orthotopic anaplastic thyroid carcinoma xenografts in vitro and in vivo. Erbitux potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan and achieved 93% in vivo inhibition of tumour growth when combined with irinotecan, compared to 77% and 79% inhibition when cetuximab and irinotecan were used alone, respectively.

Trade Name Erbitux
Availability Prescription only
Generic Cetuximab
Cetuximab Other Names Cetuximab, Cétuximab, Cetuximabum
Related Drugs methotrexate, Keytruda, capecitabine, pembrolizumab, Avastin, Opdivo, Xeloda, nivolumab, Trexall, bleomycin
Weight 5mg/ml, , 2mg/ml
Type Injection, Infusion, Intravenous Solution
Formula C6484H10042N1732O2023S36
Weight 145781.6 Da
Protein binding

There is no information available.

Groups Approved
Therapeutic Class Targeted Cancer Therapy
Manufacturer Merck Limited, E Merck India, Merck Private Ltd, , Pt Merck Indonesia
Available Country India, Pakistan, United Kingdom, Canada, Australia, United States, Indonesia, France, Italy, Netherlands, Portugal, Spain,
Last Updated: September 19, 2023 at 7:00 am
Erbitux
Erbitux

Uses

Squamous Cell Carcinoma Of The Head And Neck (SCCHN): Erbitux is used for combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck.

Erbitux is used for combination with platinum-based therapy with 5-FU for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinomaof the head and neck.

Erbitux, as a single agent, is used for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed.

K-Ras Wild-Type, EGFR-Expressing Colorectal Cancer: Erbitux is used for the treatment of K-Ras wild-type, epidermal growth factor receptor (EGFR)- expressing, metastatic colorectal cancer (mCRC) as determined by FDA-approved tests for this use

  • In combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment
  • In combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy
  • As a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.

Erbitux is also used to associated treatment for these conditions: Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN), Metastatic Colorectal Cancer (MCRC), Metastatic Squamous Cell Carcinoma of the Head and Neck, Recurrent Squamous Cell Carcinoma of the Head or Neck, Regionally Advanced Squamous Cell Carcinoma of the Head and Neck

How Erbitux works

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a type I receptor tyrosine kinase expressed on both normal and malignant cells. It has been investigated as a therapeutic target for anticancer treatment, as it is often upregulated in cancer types, including head and neck, colon, and rectal cancers. When activated by its ligand, EGFR undergoes a conformational change and dimerization to form homodimers or heterodimers with another member of the ErbB family of receptors. Dimerization of EGFR activates the intracellular tyrosine kinase region of EGFR and promotes autophosphorylation, initiating a series of downstream signalling cascades, including cell differentiation, proliferation, migration, angiogenesis, and apoptosis. This EGFR signalling pathway is often dysregulated in cancer cells, leading to aberrant cell growth and enhanced cell survival.

Erbitux is a monoclonal antibody that binds specifically to the EGFR on both normal and tumour cells to competitively inhibit the binding of epidermal growth factor (EGF) and other ligands that are produced by normal and tumour tissue epithelial cells. Upon binding to domain III of EGFR - which is the binding site for its growth factor ligands - cetuximab prevents the receptor from adopting an extended conformation and thereby inhibits EGFR activation, as well as phosphorylation and activation of receptor-associated kinases (MAPK, PI3K/Akt, Jak/Stat). Inhibition of the EGFR signalling pathway ultimately leads to inhibition of cell cycle progression, cell survival pathways, and tumour cell motility and invasion. Erbitux also induces cell apoptosis and decreases matrix metalloproteinase and vascular endothelial growth factor (VEGF) production. In vitro, cetuximab was shown to inhibit tumour angiogenesis. Binding of cetuximab to EGFR also results in internalization of the antibody-receptor complex, leading to an overall downregulation of EGFR expression.

K-ras is a small G-protein downstream of EGFR that plays an important role in promoting the EGFR signalling cascade: in some malignant cells, K-ras can acquire activating mutations in exon 2 and thus be continuously active regardless of EGFR regulation. Since mutant Ras proteins can isolate the pathway from the effect of EGFR, K-Ras mutations can render EGFR inhibitors like cetuximab ineffective in exerting anti-tumour effects. Erbitux is thus only limited in its use for K-Ras wild-type, EGFR-expressing cancers.

Dosage

Erbitux dosage

Squamous Cell Carcinoma Of The Head And Neck:

Erbitux in combination with radiation therapy or in combination with platinum-based therapy with 5-FU:

  • The recommended initial dose is 400 mg/m2 administered one week prior to initiation of a course of radiation therapy or on the day of initiation of platinum-based therapy with 5-FU as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min). Complete Erbitux administration 1 hour prior to platinum-based therapy with 5-FU.
  • The recommended subsequent weekly dose (all other infusions) is 250 mg/m2infused over 60 minutes (maximum infusion rate 10 mg/min) for the duration of radiation therapy (6–7 weeks) or until disease progression or unacceptable toxicity when administered in combination with platinum-based therapy with 5-FU. Complete Erbitux administration 1 hour prior to radiation therapy or platinumbased therapy with 5-FU.

Erbitux monotherapy:

  • The recommended initial dose is 400 mg/m2administered as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min).
  • The recommended subsequent weekly dose (all other infusions) is 250 mg/m2infused over 60 minutes (maximum infusion rate 10 mg/min) until disease progression or unacceptable toxicity.

Colorectal Cancer:

  • Determine EGFR-expression status using FDA-approved tests prior to initiating treatment. Also confirm the absence of aRasmutation prior to initiation of treatment with Erbitux.
  • The recommended initial dose, either as monotherapy or in combination with irinotecan or FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), is 400 mg/m2administered as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min). Complete Erbitux administration 1 hour prior to FOLFIRI.
  • The recommended subsequent weekly dose, either as monotherapy or in combination with irinotecan or FOLFIRI, is 250 mg/m2infused over 60 minutes (maximum infusion rate 10 mg/min) until disease progression or unacceptable toxicity. Complete Erbitux administration 1 hour prior to FOLFIRI.

Recommended Premedication: Premedicate with an H1antagonist(eg, 50 mg ofdiphenhydramine) intravenously 30–60 minutes prior to the first dose; premedication should be administered for subsequent Erbitux doses based upon clinical judgment and presence/severity of prior infusion reactions.

Do not administer cetuximab as an intravenous push or bolus. Administer via infusion pump or syringe pump. Do not exceed an infusion rate of 10 mg/min. Administer through a low protein binding 0.22-micrometer in-line filter.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates. Do not s hake or dilute.

Side Effects

Fatigue, pain, headache, fever, confusion, anxiety, insomnia, chills, rigors, depression. Acneiform rash, rash, dry skin, pruritus, nail changes, hypomagnesaemia, abdominal pain, constipation, diarrhoea, vomiting, nausea, wt loss, weakness, bone pain.

Toxicity

The intravenous LD50 is > 300 mg/kg in mice and > 200 mg/kg in rats. There is limited information on the overdose from cetuximab.

In clinical trials, cetuximab was associated with serious and fatal infusion reactions, cardiopulmonary arrest or sudden death, and serious dermatologic toxicities. Pulmonary toxicities, such as interstitial lung disease, interstitial pneumonitis with non-cardiogenic pulmonary edema, and exacerbation of pre-existing fibrotic lung disease have been reported.

Precaution

Infusion rate should be reduced if patient exhibits signs of toxicity. Discontinue treatment if there is severe infusion reactions. Caution when used in patients with history of coronary artery disease, heart failure and arrhythmias. Monitor serum electrolytes during and after (for at least 8 wk) cetuximab therapy. Exposure to sunlight may worsen skin reactions. Risk of interstitial lung disease in patients with preexisting lung disease. Dose should be modified if there is occurrence of severe acneiform rash, refer to product insert/SPG for dosing guidelines.

Food Interaction

No interactions found.

Volume of Distribution

The volume of the distribution is about 2-3 L/m2 and is independent of dose.

Elimination Route

After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the steady-state levels of cetuximab was reached by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 µg/mL to 235 µg/mL and 41 µg/mL to 85 µg/mL, respectively. Tmax is about 3 hours.

Half Life

After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the mean half-life for cetuximab was approximately 112 hours, with a range of 63 to 230 hours.

Clearance

In patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the estimated clearance rate was 0.103 L/h. At doses ranging from 200 to 400 mg/m2

Elimination Route

There is limited information available.

Pregnancy & Breastfeeding use

Pregnancy: category C. Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether Erbitux is secreted in human milk. IgG antibodies, such as Erbitux, can be excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Erbitux, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If nursing is interrupted, based on the mean half-life of cetuximab, nursing should not be resumed earlier than 60 days following the last dose of Erbitux.

Special Warning

Dose modification in cases of severe acneiform rash (grade 3 or 4):

  • 1st occurrence: Delay infusion by 1-2 wk. If improvement, continue at 250 mg/m2; discontinue if no improvement.
  • 2nd occurrence: Delay infusion by1-2 wk. If improvement, continue at reduced dose of 200 mg/m2; discontinue if no improvement.
  • 3rd occurrence: Delay infusion by 1-2 wk. If improvement, continue at reduced dose of 150 mg/m2; discontinue if no improvement. 4th occurrence: Discontinue therapy.

Acute Overdose

The maximum single dose of cetuximab administered is 1000 mg/m2 in one patient. No adverse events were reported for this patient.

Storage Condition

Store vials under refrigeration at 2° to 8° C. Do not freeze.

Innovators Monograph

You find simplified version here Erbitux

Erbitux contains Cetuximab see full prescribing information from innovator Erbitux Monograph, Erbitux MSDS, Erbitux FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
Share