ERBITUX 5 mg/ml SOLUTION FOR INFUSION

Introduction

Prospective: Information for the User

Erbitux 5mg/ml solution for infusion

cetuximab

Read the entire prospectus carefully before starting to use this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are not listed in this prospectus. See section 4.

Contents of the Prospectus

1. What is Erbitux and what is it used for
2. What you need to know before starting to use Erbitux
3. How to use Erbitux
4. Possible adverse effects
5. Storage of Erbitux
6. Package contents and additional information

1. What is Erbitux and what is it used for

What is Erbitux

Erbitux contains cetuximab, a monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind specifically to other unique proteins, called 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 signaling pathway, a complex cascade involved in the development and progression of cancer. 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 these 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 radiotherapy or other anticancer medications.

2. What you need to know before starting to use Erbitux

Do not use Erbitux

Do not use Erbitux if you have ever had 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. You should not receive Erbitux in combination with other anticancer treatments that include oxaliplatin 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 of the following information is unclear.

Erbitux may cause infusion-related adverse effects. These reactions may be allergic in nature. Read the "Infusion-related adverse effects" section of section 4 for detailed information, as they can have serious consequences for you, including life-threatening situations. These adverse effects usually occur during infusion, during the following hour, or sometimes after this period. To detect the first signs of these effects, you will be regularly examined while receiving each Erbitux infusion and for at least 1 hour after the end of it.

You are more likely to experience severe allergic reactions if you are allergic to red meat or tick bites, or if you have tested positive for certain antibodies (detected in a test). Your doctor will discuss the appropriate measures with you.

Erbitux may cause adverse effects that affect the skin. Your doctor will discuss with you whether you may need any preventive measures or early treatment. Also, read "Skin-related adverse effects" in section 4 for more detailed information, as some skin reactions can have serious consequences for you, even life-threatening.

If you have heart problems, your doctor will discuss with you whether you can receive Erbitux in combination with other anticancer 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, redness of the eyes, and/or severe dry eye, if you have had these problems in the past or if you use contact lenses. Your doctor will discuss with you whether you should consult a specialist.

If you receive Erbitux in combination with anticancer medications, including platinum, you are more likely to have a decreased number of white blood cells in your blood. Therefore, your doctor may monitor your blood and general condition to detect signs of infection (see also "Adverse effects that occur when combined with other anticancer treatments" in section 4).

If you receive Erbitux in combination with other anticancer medications, including fluoropyrimidines, you may be more likely to experience heart problems that could be life-threatening. Your doctor will discuss with you whether you may need special monitoring (see also the "Adverse effects that occur when combined with other anticancer treatments" section of section 4).

Children and adolescents

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

Other medications and Erbitux

Tell your doctor if you are taking, have recently taken, or may need to take any other medication, including those purchased 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 discuss 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 for 2 months after the last administration.

Driving and using machines

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

3. How to use Erbitux

Treatment with Erbitux will be supervised by a doctor with experience in the use of anticancer medications. Regular monitoring is required during infusion and for at least 1 hour after the end of it, to detect the first signs of a possible infusion-related adverse effect.

Pre-treatment

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

Dosage and administration

Erbitux is usually administered through a vein (given by infusion). Your doctor will calculate the appropriate dose of Erbitux for you. The dose of Erbitux 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 over approximately 2 hours. Each subsequent dose (250 mg/m² of body surface area) is infused over approximately 1 hour.

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

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

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

Duration of treatment

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

Combination with other anticancer treatments

If you receive Erbitux in combination with other anticancer medications, these medications should be administered at least 1 hour after the end of the Erbitux infusion.

If you receive Erbitux in combination with radiotherapy, treatment with Erbitux usually starts one week before radiotherapy.

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

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people experience them.

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

Infusion-related adverse effects

It is likely that more than 10 out of 100 patients will experience infusion-related adverse effects; being severe in more than 1 out of 100 patients. These reactions may be allergic in nature. They usually occur during infusion, during the following hour, or sometimes after this period.

Mild or moderate infusion-related adverse effectsare:

• fever
• chills
• dizziness
• difficulty breathing

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

Severe infusion-related adverse effectsare:

• severe difficulty breathing that occurs rapidly
• urticaria
• fainting
• chest pain (a symptom of heart-related adverse effects)

If you experience these symptoms, inform your doctor immediately.These adverse effects can have serious consequences, which can even be life-threatening in rare cases, and require immediate medical attention. Treatment with Erbitux should then be discontinued.

Skin-related adverse effects

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

The main skin-related adverse effects are:

• acne-like skin changes
• itching
• dry skin
• peeling
• excessive hair growth
• nail changes (e.g., inflammation of the nail bed)

In very rare cases (affecting up to 1 in 10,000 people), patients may experience blistering 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 immediatelybecause these signs can have serious consequences, including life-threatening conditions.

If you notice other extensive skin changes, consult your doctor as soon as possibleas it may be necessary to modify the dose of Erbitux or the time between infusions. Your doctor will decide whether to discontinue treatment in case of repeated skin reactions after several dose reductions.

If you notice 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 can indicate a skin infection, which can have serious consequences, including life-threatening conditions.

Lung-related adverse effects

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

If you notice symptoms such as 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 adverse effects

Very common adverse effects(affecting more than 1 in 10 people)

• inflammation of the tissue that lines the intestines, mouth, and nose (in some cases severe), which can cause nasal bleeding in some patients
• decrease in blood magnesium levels
• increase in blood levels of certain liver enzymes

Common adverse effects(affecting 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, leading to weight loss
• decrease in blood calcium levels

Uncommon adverse effects(affecting 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)

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

• inflammation of the brain lining (aseptic meningitis)

Adverse effects that occur when combined with other anticancer treatments

If you receive Erbitux in combination with other anticancer medications, some of the adverse effects you may experience may be related to the combination or to the other medications. Therefore, make sure to also read the prospectus of the other medications.

If you receive Erbitux in combination with anticancer medications, including platinum, you are more likely to have a decreased number of white blood cells in your blood. This can lead to infectious complications, which can even be life-threatening, 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 an anticancer medication that contains fluoropyrimidines, you are likely to experience the following adverse 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 the skin to peel (hand-foot syndrome)

If you receive Erbitux with radiotherapy, some of the adverse effects you may experience may be related to this combination, such as:

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

Reporting adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Medication Monitoring System for Human Use: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Erbitux

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

Do not use this medication after the expiration date shown on the label and carton after "EXP". The expiration date is the last day of the month indicated.

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

6. Container Content and Additional Information

Composition of Erbitux

• The active ingredient is cetuximab.

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

Each 20 ml vial contains 100 mg of cetuximab.

Each 100 ml vial contains 500 mg of cetuximab.

• The other components are sodium chloride, glycine, polysorbate 80, citric acid monohydrate, sodium hydroxide, and water for injectable preparations.

Appearance of the Product and Container Content

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

Each container contains 1 vial.

Only some vial sizes may be marketed.

Marketing Authorization Holder

Merck Europe B.V.

Gustav Mahlerplein 102

1082 MA Amsterdam

Netherlands

Manufacturer

Merck Healthcare KGaA

Frankfurter Straße 250

64293 Darmstadt

Germany

Date of thelast revision of thisleaflet: 12/2024

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

Instructions for Use and Handling

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

Erbitux 5 mg/ml is compatible

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

The physical and chemical stability of Erbitux 5 mg/ml has been demonstrated during its use for 48 hours at 25°C, provided 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. Precautions should be taken to ensure aseptic conditions when preparing the infusion. Erbitux 5 mg/ml should be prepared as follows:

• For administration with an infusion pump or gravity drip (diluted with sterile 9 mg/ml [0.9%] sodium chloride solution): Take a sodium chloride 9 mg/ml (0.9%) sterile infusion bag of suitable size. Calculate the required volume of Erbitux. Withdraw the appropriate volume of sodium chloride solution from the infusion bag using a suitable sterile syringe with a suitable needle. Take a suitable sterile syringe and attach a suitable 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 prime it with diluted Erbitux before starting the infusion. Use a gravity drip system or an infusion pump for administration.

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

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

Every two weeks infusionfor the treatment of squamous cell carcinoma of the head and neck when used in combination with other anti-cancer medicines and metastatic colorectal cancer:

The initial and subsequent doses (500 mg/m² body surface area) are infused over approximately 2 hours with an infusion rate not exceeding 10 mg/min.

• For administration with an infusion pump or gravity drip (undiluted): Calculate the required volume of Erbitux. Take a suitable sterile syringe (minimum 50 ml) and attach a suitable needle. Withdraw the required volume of Erbitux from a vial. Transfer Erbitux to an empty sterile bag or container. Repeat this procedure until the calculated volume is reached. Connect the infusion line and prime it 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 (400 mg/m² body surface area) is infused over approximately 2 hours. Each subsequent dose (250 mg/m² body surface area) is infused over approximately 1 hour with an infusion rate not exceeding 10 mg/min.

Every two weeks infusionfor the treatment of squamous cell carcinoma of the head and neck when used in combination with other anti-cancer medicines and metastatic colorectal cancer:

The initial and subsequent doses (500 mg/m² body surface area) are infused over approximately 2 hours with an infusion rate not exceeding 10 mg/min.

• For administration with a syringe pump: Calculate the required volume of Erbitux. Take a suitable sterile syringe and attach a suitable needle. Withdraw the required volume of Erbitux from a vial. Remove the needle and insert the syringe into the syringe pump. Connect the infusion line to the syringe and start the infusion after priming the line with Erbitux or with a sterile 9 mg/ml (0.9%) sodium chloride injection solution. Repeat this procedure until the calculated volume has been infused.

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

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

Every two weeks infusionfor the treatment of squamous cell carcinoma of the head and neck when used in combination with other anti-cancer medicines and metastatic colorectal cancer:

• The initial and subsequent doses (500 mg/m² body surface area) are infused over approximately 2 hours with an infusion rate not exceeding 10 mg/min.