Erbitux 5 mg/ml solution for infusion

What Erbitux is

Erbitux contains cetuximab, a monoclonal antibody. Monoclonal antibodies are proteins thatspecifically recognise and bind to other unique proteins called antigens. Cetuximab binds to theepidermal growth factor receptor (EGFR), an antigen on the surface of certain cancer cells. As a resultof this binding, the cancer cell can no longer receive the messages it needs for growth, progression andmetastasis.

What Erbitux is used for

Erbitux is used to treat two different types of cancer:

• metastatic cancer of the large intestine. In these patients, Erbitux is used alone or incombination with other anticancer medicines.
• a certain type of cancer of the head and neck (squamous cell cancer). In these patients, Erbituxis used in combination with radiation therapy or with other anticancer medicines.

Do not use Erbitux

Do not use Erbitux if you have ever had a severe hypersensitivity (allergic) reaction to cetuximab.

Take special care with Erbitux

Erbitux may cause infusion-related side effects. Such reactions may be allergic in nature. Please read'Infusion-related side effects' in section 4 for details, as they may have serious consequences for you,including life-threatening conditions. These side effects normally occur during the infusion, within1 hour afterwards, or sometimes also after this period. To recognise early signs of such effects, yourcondition will be checked regularly while you receive each infusion of Erbitux and for at least 1 hourafterwards.

If you receive Erbitux in combination with anticancer medicines including platinum, it is more likelythat your white blood cell count may be reduced. Your doctor will therefore monitor your blood andgeneral condition for signs of infection (see also 'Side effects in combination with other anticancertreatments' in section 4).

If you receive Erbitux in combination with other anticancer medicines, including fluoropyrimidines,it may be more likely that you experience heart problems which may be life-threatening. Your doctorwill discuss with you whether you may need any particular supervision (see also 'Side effects incombination with other anticancer treatments' in section 4).

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, includingmedicines obtained without a prescription.

Pregnancy

Tell your doctor if you are pregnant or if you are not using reliable contraception (speak to your doctorif you are not sure). Your doctor will then discuss with you the risks and benefits of using Erbitux inthese situations.

Breast-feeding

Do not breast-feed your baby during the period over which you are being treated with Erbitux and fortwo months after the last dose.

Driving and using machines

Do not drive or use any tools or machines if you experience treatment-related symptoms that affectyour ability to concentrate and react.

A doctor experienced in the use of anticancer medicines will supervise your Erbitux therapy. Duringeach infusion and for at least 1 hour afterwards, your condition will be checked regularly for earlysigns of a possible infusion-related side effect.

Pre-treatment

Before the first dose, you will receive an antiallergic medicine in order to reduce the risk of an allergicreaction. Your doctor will decide whether such pre-treatment is necessary for subsequent doses.

Dosage and administration

Erbitux is usually infused into a vein (given as a drip) once a week. Your doctor will calculate thecorrect dose of Erbitux for you because it depends on your body surface area. The first dose (400 mg/m² body surface area) is infused over a period of approximately 2 hours. Each subsequent dose(250 mg/m²) is infused in approximately 1 hour. Erbitux must not be infused more rapidly than 10 mg/min.

Detailed instructions for your doctor or your nurse on how to prepare the Erbitux infusion are includedat the end of this package leaflet (see 'Handling instructions').

Duration of treatment

Erbitux is usually infused once a week. The duration of treatment may vary depending on your diseaseas well as from person to person and your doctor will therefore discuss with you how long you willreceive Erbitux.

Combination with other anticancer treatments

If you receive Erbitux in combination with other anticancer medicines, these medicines must beadministered at least 1 hour after the end of the Erbitux infusion.

If you receive Erbitux in combination with radiation therapy, treatment with Erbitux is usually startedone week before radiation therapy.

Like all medicines, Erbitux can cause side effects, although not everybody gets them.

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

Infusion-related side effects

More than 10 out of 100 patients are likely to experience infusion-related side effects; in more than 1out of 100 patients these side effects are likely to be severe. Such reactions may be allergic in nature.They normally occur during the infusion, within 1 hour afterwards, or sometimes also after this period.

Mild or moderate infusion-related side effects include:

• fever
• chills
• dizziness
• breathing difficulties If such symptoms occur, please inform your doctor as soon as possible. Your doctor may considerreducing the infusion rate of Erbitux to manage these symptoms.

Severe infusion-related side effects include:

• severe breathing difficulties which develop rapidly
• hives
• fainting
• chest pain (a symptom of side effects on your heart) If such symptoms occur, speak to a doctor immediately. These side effects may have seriousconsequences, in rare cases including life-threatening conditions, and require immediate attention.Treatment with Erbitux must then be stopped.

Side effects concerning the skin

More than 80 out of 100 patients are likely to experience side effects involving the skin. In about15 out of 100 patients these skin reactions are likely to be severe. Most of these side effects developwithin the first three weeks of treatment. They usually disappear over time after the end of Erbituxtherapy.

Main side effects concerning the skin include:

• acne-like skin alterations
• itching
• dry skin
• scaling
• excessive growth of hair
• nail disorders, for example inflammation of the nail bed

If you notice extensive skin alterations, please inform your doctor as soon as possible because theErbitux dose or the time between infusions may need to be changed. Your doctor will decide whethertreatment has to be stopped if skin reactions reappear after several dose reductions.

If you notice that already affected areas of your skin get worse, speak to a doctor immediately,especially if you also experience general signs of infection such as fever and tiredness. These signsmay indicate a skin infection, which may have serious consequences including life-threateningconditions.

Other side effects

Very common side effects (may affect more than 1 user in 10)

• inflammation of the lining of the intestine, mouth, and nose which may lead to nose bleeding insome patients
• decrease in blood levels of magnesium
• increase in blood levels of certain liver enzymes

Common side effects (may affect 1 to 10 users in 100)

• headache
• tiredness
• irritation and redness of the eye
• diarrhoea
• drying out which may be due to diarrhoea or reduced fluid intake
• feeling sick
• vomiting
• loss of appetite, leading to weight decrease
• decrease in blood levels of calcium

Uncommon side effects (may affect 1 to 10 users in 1,000)

• blood clots in the veins of the legs
• blood clots in the lungs
• inflammation of the eye lid or the front part of the eye

Side effects of which the frequency is not known

• inflammation of the lining of the brain (aseptic meningitis)

Side effects in combination with other anticancer treatments

If you receive Erbitux in combination with other anticancer medicines, some of the side effects youmay experience can also be related to the combination or the other medicines. Therefore, please makesure that you also read the package leaflet for the other medicines.

If you receive Erbitux in combination with anticancer medicines including platinum, it is more likelythat your white blood cell count may be reduced. This may lead to infectious complications includinglife-threatening conditions, especially if you experience skin reactions, inflammation of the lining ofthe intestine and mouth or diarrhoea. Therefore, if you experience general signs of infection such asfever and tiredness, please speak to a doctor immediately.

If you receive Erbitux in combination with an anticancer medicine containing fluoropyrimidines, it ismore likely that you experience the following side effects of this other medicine:

• chest pain
• heart attack
• heart failure
• redness and swelling of the palms of the hands or the soles of the feet which may cause the skinto peel (hand-foot syndrome)

If you receive Erbitux with radiation therapy, some of the side effects you may experience can also berelated to this combination, such as:

• inflammation of the lining of the intestine and mouth
• skin reactions typical for radiation therapy
• difficulty in swallowing
• reduction in the number of white blood cells

Keep out of the reach and sight of children.

Do not use Erbitux after the expiry date which is stated on the label and the carton after EXP. Theexpiry date refers to the last day of that month.

Store in a refrigerator (2°C - 8°C).

Once opened, Erbitux is intended for immediate use.

What Erbitux contains

• The active substance is cetuximab.Each ml of the solution for infusion contains 5 mg cetuximab.Each vial of 10 ml contains 50 mg cetuximab.Each vial of 20 ml contains 100 mg cetuximab.Each vial of 50 ml contains 250 mg cetuximab.Each vial of 100 ml contains 500 mg cetuximab.
• The other ingredients are sodium chloride, glycine, polysorbate 80, citric acid monohydrate,sodium hydroxide and water for injections.

What Erbitux looks like and contents of the pack

Erbitux 5 mg/ml solution for infusion is supplied in vials containing 10 ml, 20 ml, 50 ml or 100 ml.Each pack contains 1 vial.
Not all vial sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Merck KGaA
64271 Darmstadt
Germany

This leaflet was last approved in MM/YYYY.

The following information is intended for medical or healthcare professionals only:

Handling instructions

Erbitux may be administered via a gravity drip, an infusion pump or a syringe pump. Since Erbituxis only compatible with sterile sodium chloride 9 mg/ml (0.9%) solution for injection, it must not bemixed with other intravenously applied medicinal products. A separate infusion line must be used forthe infusion, and the line must be flushed with sterile sodium chloride 9 mg/ml (0.9%) solution forinjection at the end of 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), polyolefinethermoplastic (TP) or polyvinyl chloride (PVC) infusion sets,
• with polypropylene (PP) syringes for syringe pump.

Erbitux 5 mg/ml is chemically and physically stable for up to 48 hours at 25°C, if the solution isprepared as described hereafter. However, since it does not contain any antimicrobial preservative orbacteriostatic agent, it is intended for immediate use. Care must be taken to ensure aseptic handlingwhen preparing the infusion. Erbitux 5 mg/ml must be prepared as follows:

• For administration with infusion pump or gravity drip (diluted with sterile sodium chloride9 mg/ml (0.9%) solution): Take an infusion bag of adequate size of sterile sodium chloride9 mg/ml (0.9%) solution. Calculate the required volume of Erbitux. Remove an adequatevolume of the sodium chloride solution from the infusion bag, using an appropriate sterilesyringe with a suitable needle. Take an appropriate sterile syringe and attach a suitable needle.Draw up the required volume of Erbitux from a vial. Transfer the Erbitux into the preparedinfusion bag. Repeat this procedure until the calculated volume has been reached. Connect theinfusion line and prime it with the diluted Erbitux before starting the infusion. Use a gravitydrip or an infusion pump for administration. The first dose is 400 mg/m² body surface areainfused over a period of approximately 2 hours. Each subsequent dose is 250 mg/m² infused inapproximately 1 hour. Erbitux must not be infused more rapidly than 10 mg/min.
• For administration with infusion pump or gravity drip (undiluted): Calculate the requiredvolume of Erbitux. Take an appropriate sterile syringe (minimum 50 ml) and attach a suitableneedle. Draw up the required volume of Erbitux from a vial. Transfer the Erbitux into a sterileevacuated container or bag. Repeat this procedure until the calculated volume has been reached.Connect the infusion line and prime it with Erbitux before starting the infusion. The first dose is400 mg/m² body surface area infused over a period of approximately 2 hours. Each subsequentdose is 250 mg/m² infused in approximately 1 hour. Erbitux must not be infused more rapidlythan 10 mg/min.
• For administration with a syringe pump: Calculate the required volume of Erbitux. Take anappropriate sterile syringe and attach a suitable needle. Draw up the required volume of Erbituxfrom a vial. Remove the needle and put the syringe into the syringe pump. Connect the infusionline to the syringe and start the infusion after priming the line with Erbitux or sterile sodiumchloride 9 mg/ml (0.9%) solution. Repeat this procedure until the calculated volume has beeninfused. The first dose is 400 mg/m² body surface area infused over a period of approximately2 hours. Each subsequent dose is 250 mg/m² infused in approximately 1 hour. Erbitux must notbe infused more rapidly than 10 mg/min.