Patient Information

Erbitux 5mg/ml Infusion Solution

cetuximab

Read this entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, talk to your doctor, evenif they are not listed in this leaflet.See section4.

1.What Erbitux is and what it is used for

2.What you need to know before using Erbitux

3.How to use Erbitux

4.Possible side effects

5.Storage of Erbitux

6.Contents of the pack and additional information

What is Erbitux

Erbitux contains cetuximab, a monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind specifically to other unique proteins, known as antigens. Cetuximab binds to the epidermal growth factor receptor (EGFR), an antigen found on the surface of certain cancer cells. The EGFR activates proteins called RAS. The RAS proteins play an important role in the EGFR pathway, a complex signaling cascade involved in cancer development and progression. As a result of this binding, the cancer cell can no longer receive the messages it needs for growth, progression, and metastasis.

What is Erbitux used for

Erbitux is used to treat two different types of cancer:

• Metastatic colorectal cancer. In those patients, Erbitux is used alone or in combination with other anticancer medications.

• A specific type of head and neck cancer (squamous cell carcinoma). In these patients, Erbitux is used in combination with radiation therapy or with other anticancer medications.

No use Erbitux

No use Erbitux if you have ever experienced a severe hypersensitivity reaction (allergic) to cetuximab.

Before starting treatment for metastatic colorectal cancer, your doctor will analyze your cancer cells to see if they contain the normal (native) or mutant form of the RAS gene. Do not receive Erbitux in combination with other cancer treatments that include oxaliplatino if your cancer cells contain the mutant form of the RAS gene.

Warnings and precautions

Consult your doctor before starting to use Erbitux, if any part of the following information is not clear.

Erbitux may cause infusion-related adverse effects. These reactions may be allergic in nature. Read the section “Infusion-related adverse effects” in section 4 for detailed information, as they may have severe consequences for you, even life-threatening situations. These adverse effects usually appear during infusion, within the next hour, or sometimes also after this period. To detect the first signs of these effects, you will be regularly examined while receiving each infusion of Erbitux and for at least 1 hour after the end of the same.

You are more likely to suffer severe allergic reactions if you are allergic to red meat or tick bites, or if you presented positive results for certain antibodies (detected in a test). Your doctor will comment on the appropriate measures.

Erbitux may cause adverse effects that affect the skin. Your doctor will comment if you may need any type of preventive measures or early treatment. Read also “Adverse effects that affect the skin” in section 4 for more detailed information, as some skin reactions may have severe consequences for you, even putting your life at risk.

If you have heart problems, your doctor will comment if you can receive Erbitux in combination with other cancer medications, especially if you are 65 years or older.

Erbitux may cause adverse effects that affect the eyes. Inform your doctor if you experience worsening of your eye problems or acute eye problems, such as blurred vision, eye pain, eye redness, and/or severe eye dryness, if you have had those problems in the past or if you use contact lenses. Your doctor will comment if you should consult a specialist.

If you receive Erbitux in combination with cancer medications, including platinum, it is more likely that the number of white blood cells in your blood will be decreased. Therefore, your doctor may monitor your blood and general condition to detect signs of infection (see also “Adverse effects that appear when combined with other cancer treatments” in section 4).

If you receive Erbitux in combination with other cancer medications, including fluoropyrimidines, you may be more likely to experience heart problems that could pose a threat to your life. Your doctor will comment if you may need any type of special supervision (see also the section “Adverse effects that appear when combined with other cancer treatments” in section 4).

Children and adolescents

There is no specific recommendation for the use of Erbitux in the pediatric population.

Other medications and Erbitux

Inform your doctor if you are taking, have recently taken, or may need to take any other medication, even those acquired without a prescription.

Pregnancy

If you are pregnant or if you are not using a reliable contraceptive method (consult your doctor if you have doubts), inform your doctor. Your doctor will analyze with you the possible risks or benefits of using Erbitux in these situations.

Breastfeeding

Do not breastfeed your child during the time you are being treated with Erbitux or during the two months following the last administration.

Driving and operating machinery

Do not drive or operate tools or machines if you experience symptoms related to treatment that impair your ability to concentrate and react.

The treatment with Erbitux will be supervised by a doctor with experience in the use of cancer medications. Regular monitoring is required during infusion and for at least 1 hour after its completion, to detect the first signs of a possible adverse effect related to the infusion.

Pre-treatment

Before the first dose, you will receive an anti-allergic medication to reduce the risk of allergic reactions. Your doctor will decide if it is necessary to repeat this treatment in subsequent infusions.

Dosage and administration

Erbitux is usually administered through a vein (infused via drip). Your doctor will calculate the appropriate dose of Erbitux for you. The Erbitux dose depends on your body surface area and whether you receive Erbitux once a week or once every two weeks.

Weekly infusion for the treatment of squamous cell carcinoma of the head and neck and metastatic colorectal cancer:

The initial dose (400 mg/m² of body surface area) is infused for approximately 2 hours. Each subsequent dose (250 mg/m² of body surface area) is infused for approximately 1 hour.

Infusion every two weeks for the treatment of squamous cell carcinoma of the head and neck when used in combination with other anti-neoplastic medications and metastatic colorectal cancer:

The Erbitux dose (500 mg/m² of body surface area) is infused for approximately 2 hours.

At the end of this prospectus, the instructions that your doctor or nurse should follow in preparing the Erbitux infusion are detailed (see "Instructions for use and handling").

Treatment duration

Erbitux is usually administered once a week. The treatment duration may vary depending on your disease or patient to patient, so your doctor will discuss with you the time you should be on Erbitux treatment.

Combination with other cancer treatments

If you receive Erbitux in combination with other cancer medications, these medications must be administered at least 1 hour after the completion of the Erbitux infusion.

If you receive Erbitux in combination with radiation therapy, the Erbitux treatment usually starts one week before radiation therapy.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The main side effects of Erbitux are infusion-related side effects and skin-related side effects:

Infusion-related side effects

It is likely that more than 10 out of 100 patients will experience infusion-related side effects, with severe side effects occurring in more than 1 in 100 patients. These reactions can be allergic in nature. They usually appear during infusion, within the next hour, or sometimes even after this period.

Mild or moderate infusion-related side effectsare the following:

• fever
• chills
• dizziness
• difficulty breathing

If these symptoms appear, consult your doctor as soon as possible.Your doctor may consider reducing the infusion rate of Erbitux to control these symptoms.

Severe infusion-related side effectsare the following:

• severe difficulty breathing that appears rapidly
• urticaria
• syncope
• chest pain (a symptom of heart-related side effects)

Ifthese symptoms appear, inform your doctor immediately.These side effects can have serious consequences, which can even, in rare cases, put your life at risk and require immediate medical attention. Treatment with Erbitux should then be suspended.

Skin-related side effects

It is likely that more than 80 out of 100 patients will experience skin-related side effects. In about 15 out of 100 patients, these skin reactions (cutaneous) can be severe. Most of these side effects appear during the first three weeks of treatment. They usually disappear over time after treatment with Erbitux is discontinued.

The main skin-related side effects are the following:

• skin lesions similar to acne
• itching
• dry skin
• peeling
• excessive hair growth
• changes in nails (e.g., inflammation of the nail bed)

In very rare cases (they can affect up to 1 in 10,000 people), patients may experience the formation of blisters or peeling of the skin, which can indicate a more severe skin reaction, called "Stevens-Johnson syndrome". If you experience these symptoms, inform your doctor immediately, as these signs can have serious consequences, including life-threatening conditions.

If you observeotherextensive skin changes, consult your doctor as soon as possiblesince it may be necessary to modify the dose of Erbitux or the time between infusions. Your doctor will decide whether to discontinue treatment if skin reactions recur after several dose reductions.

If you observe that the affected skin areas worsen, inform your doctor immediately, especially if you also experience general signs of infection such as fever or fatigue. These signs may indicate a skin infection, which can have serious consequences, including life-threatening conditions.

Lung-related side effects

In rare cases (they can affect up to 1 in 100 people), patients may experience lung inflammation (interstitial lung disease), which can have serious consequences, including life-threatening conditions.

If you observe symptoms such as the onset or worsening of breathing difficulties, inform your doctor immediately, especially if you also experience cough or fever. Your doctor will decide whether to discontinue treatment.

Other side effects

Very common side effects(can affect more than 1 in 10 people)

• inflammation of the mucous membranes covering the intestines, mouth, and nose (in some cases severe), which can cause nasal bleeding in some patients
• decreased magnesium levels in the blood
• increased levels of certain liver enzymes in the blood

Common side effects(can affect up to 1 in 10 people)

• headache
• fatigue
• irritation and redness of the eyes (conjunctivitis)
• diarrhea
• dehydration, which can be due to diarrhea or decreased fluid intake
• nausea
• vomiting
• loss of appetite, which causes weight loss
• decreased calcium levels in the blood

Rare side effects(can affect up to 1 in 100 people)

• blood clots in the veins of the legs
• blood clots in the lungs
• inflammation of the eyelid or cornea (the front part of the eye)

Side effects of unknown frequency (cannot be estimated from available data)

• inflammation of the meninges (aseptic meningitis)

Side effects that appear when combined with other cancer treatments

If you receive Erbitux in combination with other cancer medications, some of the side effects you may experience may be related to the combination or to the other medications. Therefore, make sure to read the prospectus of the other medications as well.

If you receive Erbitux in combination with cancer medications, including platinum, it is more likely that the number of white blood cells in your blood will be decreased. This can lead to infectious complications, which can even put your life at risk, especially if you experience skin reactions, inflammation of the intestinal walls and mouth, or diarrhea.Therefore, if you experience general signs of infection such as fever and fatigue, inform your doctor immediately.

If you receive Erbitux in combination with a cancer medication containing fluoropyrimidines, it is likely that you will experience the following side effects related to the other medication:

• chest pain
• heart attack (myocardial infarction)
• heart failure
• redness and swelling of the palms of the hands or soles of the feet, which can cause skin peeling (hand-foot syndrome)

If you receive Erbituxtogetherwith radiation therapy, some of the side effects you may experience may be related to this combination, for example:

• inflammation of the intestinal walls and mouth
• skin reactions characteristic of radiation therapy
• difficulty swallowing
• reduction in the number of white blood cells

Reporting side effects

If you experienceany type of side effect, consult your doctor, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the box after “CAD”. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C).Once opened, Erbitux must be used immediately.

Composition of Erbitux

• The active ingredient is cetuximab.

Each milliliter of the infusion solution contains 5mg of cetuximab.

Each 20ml vial contains 100mg of cetuximab.

Each 100ml vial contains 500mg of cetuximab.

• The other components are sodium chloride, glycine, polisorbate 80, citric acid monohydrate, sodium hydroxide, and water for injection.

Appearance of the product and contents of the package

Erbitux 5mg/ml infusion solution is presented in vials of 20ml or 100ml.

Each package contains 1vial.

Only some vial sizes may be commercially available.

Marketing Authorization Holder

Merck Europe B.V.

Gustav Mahlerplein102

1082MA Amsterdam

Netherlands

Responsible for manufacturing

MerckHealthcareKGaA

Frankfurter Straße 250

64293Darmstadt

Germany

Last revision date of this leaflet: 12/2024

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

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This information is intended solely for medical professionals or healthcare professionals:

Instructions for use and handling

Erbitux can be administered by gravity infusion, infusion pump, or syringe pump. As Erbitux is only compatible with a 9mg/ml (0.9 %) sterile sodium chloride injection solution, this medicine should not be mixed with other intravenous medications. The infusion should be performed through a separate infusion line, which should be flushed with a 9mg/ml (0.9 %) sterile sodium chloride injection solution at the end of the infusion.

Erbitux 5mg/ml is compatible

• with polyethylene (PE), ethyl vinyl acetate (EVA), or PVC bags,
• with infusion equipment made of polyethylene (PE), polyurethane (PUR), ethyl vinyl acetate (EVA), thermoplastic polyolefin (TP), or PVC,
• with polypropylene (PP) syringes for syringe pump.

It has been demonstrated that the physical and chemical stability of Erbitux 5mg/ml is maintained during its use for 48 hours at 25°C, if the solution is prepared as described below. However, as it does not contain any antimicrobial preservative or bacteriostatic agent, it is intended for immediate use. It is essential to ensure aseptic conditions when preparing the infusion. Erbitux 5mg/ml should be prepared as follows:

• For administration with an infusion pump or gravity infusion (diluted with a 9mg/ml (0.9 %) sterile sodium chloride injection solution): Take a suitable infusion bag of 9mg/ml (0.9 %) sterile sodium chloride injection solution. Calculate the required volume of Erbitux. Withdraw the required volume of the sodium chloride solution from the infusion bag using a suitable sterile syringe with an appropriate needle. Take a suitable sterile syringe and connect an appropriate needle. Withdraw the required volume of Erbitux from a vial. Transfer Erbitux to the prepared infusion bag. Repeat this procedure until the calculated volume is reached. Connect the infusion line and catheter with Erbitux diluted before starting the infusion. Use a gravity infusion or infusion pump for administration.

Weekly infusionfor the treatment of squamous cell carcinoma of the head and neck and metastatic colorectal cancer:

The initial dose (400mg/m² of body surface area) is infused over approximately 2hours. Each subsequent dose (250mg/m² of body surface area) is infused over approximately 1hour at a perfusion rate not exceeding 10mg/min.

Infusion every two weeksfor the treatment of squamous cell carcinoma of the head and neck when used in combination with other antineoplastic drugs and metastatic colorectal cancer:

The initial and subsequent doses (500mg/m² of body surface area) are infused over approximately 2hours at a perfusion rate not exceeding 10mg/min.

• For administration with an infusion pump or gravity infusion (undiluted): Calculate the required volume of Erbitux. Take a suitable sterile syringe (minimum 50ml) and connect an appropriate needle. Withdraw the required volume of Erbitux from a vial. Transfer Erbitux to a suitable sterile empty bag or container. Repeat this procedure until the calculated volume is reached. Connect the infusion line and catheter with Erbitux before starting the infusion.

Weekly infusionfor the treatment of squamous cell carcinoma of the head and neck and metastatic colorectal cancer:

The initial dose (400mg/m² of body surface area) is infused over approximately 2hours. Each subsequent dose (250mg/m² of body surface area) is infused over approximately 1hour at a perfusion rate not exceeding 10mg/min.

Infusion every two weeksfor the treatment of squamous cell carcinoma of the head and neck when used in combination with other antineoplastic drugs and metastatic colorectal cancer:

• The initial and subsequent doses (500mg/m² of body surface area) are infused over approximately 2hours at a perfusion rate not exceeding 10mg/min.