Erbitux (ImClone Systems Inc)

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Erbitux (ImClone Systems Inc)® is indicated in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck.

Erbitux (ImClone Systems Inc) is indicated in combination with platinum-based therapy with 5-FU for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.

Erbitux (ImClone Systems Inc), as a single agent, is indicated 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 (ImClone Systems Inc) is indicated 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.

​Limitation of Use: Erbitux (ImClone Systems Inc) is not indicated for treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.

Erbitux (ImClone Systems Inc) injection is given with radiation treatment and other medicines to treat cancer in the colon and rectal area, and cancer in the head and neck area. Erbitux (ImClone Systems Inc) is usually given to patients who have already received other cancer treatments. Erbitux (ImClone Systems Inc) should only be used in patients with metastatic (cancer that spreads to other parts of the body) colon or rectal cancer who have had a KRAS gene mutation test. This test helps the doctor decide whether the medicine will treat their cancer.

Erbitux (ImClone Systems Inc) interferes with the growth of cancer cells, which are then destroyed by the body. Since the growth of normal body cells may also be affected by Erbitux (ImClone Systems Inc), other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, such as a skin rash, may not be serious but may cause concern. Some effects do not occur until months or years after the medicine is used.

Before you begin treatment with Erbitux (ImClone Systems Inc), you and your doctor should talk about the benefits Erbitux (ImClone Systems Inc) will do as well as the risks of using it.

Erbitux (ImClone Systems Inc) will only be given by or under the immediate supervision of your doctor.

Erbitux (ImClone Systems Inc) must be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products. Close monitoring is required during the infusion time and for at least 1 hr after the end of infusion. Resuscitation equipment must be available.

Prior to the 1st infusion, patients must receive premedication with an antihistamine and a corticosteroid. This premedication is recommended prior to all subsequent infusions.

In all indications, Erbitux (ImClone Systems Inc) is administered once a week. The very 1st dose is Erbitux (ImClone Systems Inc) 400 mg/m² body surface area with a recommended infusion period of 120 min. All subsequent weekly doses are 250 mg/m² body surface area each with a recommended infusion period of 60 min. The maximum infusion rate must not exceed 10 mg/min.

Colorectal Cancer: In patients with metastatic colorectal cancer, Erbitux (ImClone Systems Inc) is used in combination with chemotherapy or as a single agent. Detection of KRAS mutational status must be performed prior to the 1st Erbitux (ImClone Systems Inc) infusion. It is important that a validated test method is used by an experienced laboratory. For the dosage or recommended dose modifications of concomitantly used chemotherapeutic agents, please refer to the product information for these medicinal products. They must not be administered earlier than 1 hr after the end of the Erbitux (ImClone Systems Inc) infusion.

Continuation of Erbitux (ImClone Systems Inc) treatment until disease progression is recommended.

Squamous Cell Cancer of the Head and Neck: In patients with locally advanced squamous cell cancer of the head and neck, Erbitux (ImClone Systems Inc) is used concomitantly with radiation therapy. It is recommended to start Erbitux (ImClone Systems Inc) therapy 1 week before radiation therapy and to continue Erbitux (ImClone Systems Inc) therapy until the end of the radiation therapy period.

In patients with recurrent and/or metastatic squamous cell cancer of the head and neck, Erbitux (ImClone Systems Inc) is used in combination with platinum-based chemotherapy followed by Erbitux (ImClone Systems Inc) as maintenance therapy until disease progression. Chemotherapy must not be administered earlier than 1 hr after the end of Erbitux (ImClone Systems Inc) infusion.

In patients who have failed chemotherapy for recurrent and/or metastatic squamous cell cancer of the head and neck, Erbitux (ImClone Systems Inc) is also used as a single agent. Continuation of Erbitux (ImClone Systems Inc) treatment until disease progression is recommended.

Instructions for Use and Handling: Erbitux (ImClone Systems Inc) 5 mg/mL is administered IV with an infusion pump, gravity drip or a syringe pump. A separate infusion line must be used for the infusion and the line must be flushed with sterile sodium chloride 9 mg/mL (0.9%) solution for injection at the end of infusion. Erbitux (ImClone Systems Inc) 5 mg/mL is a colorless solution.

Erbitux (ImClone Systems Inc) 5 mg/mL is compatible with polyethylene (PE), ethyl vinyl acetate (EVA) or polyvinyl chloride (PVC) bags; PE,EVA,PVC, polyolefine thermoplast (TP) or polyurethane (PUR) infusion sets; polypropylene (PP) syringes for syringe pump.

Erbitux (ImClone Systems Inc) does not contain any antimicrobial preservative or bacteriostatic agent. Therefore, aseptic handling must be ensured when preparing the infusion. Immediate use after opening is strongly recommended.

Erbitux (ImClone Systems Inc) 5 mg/mL must be prepared as follows: For Administration with Infusion Pump or Gravity Drip (Diluted with Sterile Sodium Chloride 9 mg/mL (0.9%) Solution): Take an infusion bag of adequate size of sterile sodium chloride 9 mg/mL (0.9%) solution. Calculate the required volume of Erbitux (ImClone Systems Inc). Remove an adequate volume of the sodium chloride solution from the infusion bag, using an appropriate sterile syringe with a suitable needle. Take an appropriate sterile syringe and attach a suitable needle. Draw up the required volume of Erbitux (ImClone Systems Inc) from a vial. Transfer Erbitux (ImClone Systems Inc) into the prepared infusion bag. Repeat this procedure until the calculated volume has been reached. Connect the infusion line and prime it with the diluted Erbitux (ImClone Systems Inc) before starting the infusion. Use a gravity drip or an infusion pump for administration. Set and control the rate as explained previously.

For Administration with Infusion Pump or Gravity Drip (Undiluted): Calculate the required volume of Erbitux (ImClone Systems Inc). Take an appropriate sterile syringe (minimum 50 mL) and attach a suitable needle. Draw up the required volume of Erbitux (ImClone Systems Inc) from a vial. Transfer Erbitux (ImClone Systems Inc) into a sterile evacuated container or bag. Repeat this procedure until the calculated volume has been reached. Connect the infusion line and prime it with Erbitux (ImClone Systems Inc) before starting the infusion. Use a gravity drip or an infusion pump for administration. Set and control the rate as explained previously.

For administration with a Syringe Pump: Calculate the required volume of Erbitux (ImClone Systems Inc). Take an appropriate sterile syringe and attach a suitable needle. Draw up the required volume of Erbitux (ImClone Systems Inc) from a vial. Remove the needle and put the syringe into the syringe pump. Connect the infusion line to the syringe, set and control the rate as explained and start the infusion after priming the line with Erbitux (ImClone Systems Inc) or sterile sodium chloride 9 mg/mL (0.9%) solution. If necessary, repeat this procedure until the calculated volume has been infused.

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What is the most important information I should know about Erbitux (ImClone Systems Inc)?

Erbitux (ImClone Systems Inc) is often used in combination with other cancer medications and/or radiation treatments.

You should not use this medication if you are allergic to Erbitux (ImClone Systems Inc) or to mouse protein.

Before receiving Erbitux (ImClone Systems Inc), tell your doctor if you have heart rhythm problems, congestive heart failure, breathing problems, coronary artery disease, or low levels of potassium or magnesium in your blood.

After your Erbitux (ImClone Systems Inc) infusion, your doctor will need to watch you for about an hour. This is to make sure you do not have any serious side effects from the medicine.

Some people receiving a Erbitux (ImClone Systems Inc) injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel short of breath, weak or dizzy, nauseated, itchy, or have wheezing, noisy breathing, or a hoarse voice during the injection.

To make sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow-up visits to your doctor.

Avoid exposure to sunlight or tanning beds while you are receiving Erbitux (ImClone Systems Inc) and for at least 2 months after your treatment ends. Erbitux (ImClone Systems Inc) can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Use Erbitux (ImClone Systems Inc) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Erbitux (ImClone Systems Inc) is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Erbitux (ImClone Systems Inc) at home, a health care provider will teach you how to use it. Be sure you understand how to use Erbitux (ImClone Systems Inc). Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Erbitux (ImClone Systems Inc) should be a clear and colorless solution that may contain a very small amount of clear to white particles. Do not use Erbitux (ImClone Systems Inc) if it contains a large amount of particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Do not shake or dilute Erbitux (ImClone Systems Inc).
• Your doctor may give you another medicine (eg, an antihistamine, such as diphenhydramine) before you receive Erbitux (ImClone Systems Inc) to help reduce the risk of an infusion reaction. Your health care provider will monitor you for an infusion reaction while you receive Erbitux (ImClone Systems Inc) and for at least 1 hour after receiving your dose. Discuss any questions or concerns with your doctor.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Erbitux (ImClone Systems Inc), contact your doctor right away.

Ask your health care provider any questions you may have about how to use Erbitux (ImClone Systems Inc).

Use: Labeled Indications

Colorectal cancer, metastatic: Treatment of KRAS wild-type (without mutation), epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer as determined by an approved test (in combination with FOLFIRI [irinotecan, fluorouracil, and leucovorin] as first-line treatment, in combination with irinotecan [in patients refractory to irinotecan-based chemotherapy], or as a single agent in patients who have failed irinotecan- and oxaliplatin-based chemotherapy or who are intolerant to irinotecan).

Limitation of use: Erbitux (ImClone Systems Inc) is not indicated for the treatment of RAS-mutant colorectal cancer or when results of the RAS mutation tests are unknown.

Head and neck cancer, squamous cell: Treatment of squamous cell cancer of the head and neck (as a single agent for recurrent or metastatic disease after platinum-based chemotherapy failure; in combination with radiation therapy as initial treatment of locally or regionally advanced disease; in combination with platinum and fluorouracil-based chemotherapy as first-line treatment of locoregional or metastatic disease).

Off Label Uses

Colorectal cancer, metastatic, refractory (RAS wild-type, BRAF V600E-mutant)

Data from the multicenter safety lead-in portion of a phase 3 study suggest that Erbitux (ImClone Systems Inc) (in combination with encorafenib and binimetinib) may be efficacious in the treatment of metastatic RAS wild-type colorectal cancer in patients with BRAF V600E-mutant tumors and disease progression following 1 to 2 prior therapies.

See also:
What other drugs will affect Erbitux (ImClone Systems Inc)?

In combination with platinum-based chemotherapy, the frequency of severe leukopenia or severe neutropenia may be increased, and thus, may lead to a higher rate of infectious complications eg, febrile neutropenia, pneumonia and sepsis compared to platinum-based chemotherapy alone.

In combination with fluoropyrimidines, the frequency of cardiac ischaemia including myocardial infarction and congestive heart failure, as well as the frequency of hand-foot syndrome (palmar-plantar erythrodysaesthesia) were increased compared to that with fluoropyrimidines.

In combination with capecitabine and oxaliplatin (Xelox) the frequency of severe diarrhoea may be increased.

A formal interaction study showed that the pharmacokinetic characteristics of Erbitux (ImClone Systems Inc) remain unaltered after co-administration of a single dose of irinotecan (350 mg/m² body surface area). Similarly, the pharmacokinetics of irinotecan were unchanged when Erbitux (ImClone Systems Inc) was co-administered.

No other formal interaction studies with Erbitux (ImClone Systems Inc) have been performed in humans.

Incompatibilities: Erbitux (ImClone Systems Inc) must not be mixed with other medicinal products except those mentioned in Cautions for Usage.

A separate infusion line must be used.

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What are the possible side effects of Erbitux (ImClone Systems Inc)?

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

• Infusion reactions
• Cardiopulmonary arrest
• Pulmonary toxicity
• Dermatologic toxicity
• Hypomagnesemia and Electrolyte Abnormalities

The most common adverse reactions in Erbitux (ImClone Systems Inc) clinical trials (incidence ≥ 25%) include cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection.

The most serious adverse reactions with Erbitux (ImClone Systems Inc) are infusion reactions, cardiopulmonary arrest, dermatologic toxicity and radiation dermatitis, sepsis, renal failure, interstitial lung disease, and pulmonary embolus.

Across Studies 1, 3, 5, and 6, Erbitux (ImClone Systems Inc) was discontinued in 3–10% of patients because of adverse reactions.

Clinical Trials Experience

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.

The data below reflect exposure to Erbitux (ImClone Systems Inc) in 1373 patients with SCCHN or colorectal cancer in randomized Phase 3 (Studies 1 and 5) or Phase 2 (Studies 3 and 6) trials treated at the recommended dose and schedule for medians of 7 to 14 weeks.

Infusion Reactions

Infusion reactions, which included pyrexia, chills, rigors, dyspnea, bronchospasm, angioedema, urticaria, hypertension, and hypotension occurred in 15–21% of patients across studies. Grades 3 and 4 infusion reactions occurred in 2–5% of patients; infusion reactions were fatal in 1 patient.

Infections

The incidence of infection was variable across studies, ranging from 13–35%. Sepsis occurred in 1–4% of patients.

Renal

Renal failure occurred in 1% of patients with colorectal cancer.

Squamous Cell Carcinoma of the Head and Neck

Erbitux (ImClone Systems Inc) in Combination with Radiation Therapy

Table 2 contains selected adverse reactions in 420 patients receiving radiation therapy either alone or with Erbitux (ImClone Systems Inc) for locally or regionally advanced SCCHN in Study 1. Erbitux (ImClone Systems Inc) was administered at the recommended dose and schedule (400 mg/m² initial dose, followed by 250 mg/m² weekly). Patients received a median of 8 infusions (range 1–11).

Table 2: Incidence of Selected Adverse Reactions ( ≥ 10%) in Patients with Locoregionally Advanced SCCHN

Erbitux (ImClone Systems Inc) in Combination with Irinotecan

The most frequently reported adverse reactions in 354 patients treated with Erbitux (ImClone Systems Inc) plus irinotecan in clinical trials were acneiform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most common Grades 3–4 adverse reactions included diarrhea (22%), leukopenia (17%), asthenia/malaise (16%), and acneiform rash (14%).

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. Immunogenic responses to Erbitux (ImClone Systems Inc) were assessed using either a double antigen radiometric assay or an ELISA assay. Due to limitations in assay performance and sampling timing, the incidence of antibody development in patients receiving Erbitux (ImClone Systems Inc) has not been adequately determined. Non-neutralizing anti-Erbitux (ImClone Systems Inc) antibodies were detected in 5% (49 of 1001) of evaluable patients without apparent effect on the safety or antitumor activity of Erbitux (ImClone Systems Inc).

The incidence 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. For these reasons, comparison of the incidence of antibodies to Erbitux (ImClone Systems Inc) with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Erbitux (ImClone Systems Inc). Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Aseptic meningitis
• Mucosal inflammation
• Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, life-threatening and fatal bullous mucocutaneous disease

Each mL of the soln for infusion contains Cetuximab 5 mg as active substance. Each vial contains 20 mL.

Erbitux (ImClone Systems Inc) also contains the following excipients: Sodium chloride, glycine, polysorbate 80, citric acid monohydrate, sodium hydroxide and water for injection.