ERBITUX 50 ML Infusion solution

Зміст інструкції

1. Erbitux 5 mg/mL solution for infusion
   1. What is Erbitux and what is it used for
   2. What you need to know before using Erbitux
   3. How to use Erbitux
   4. Possible side effects
   5. How to store Erbitux
   6. Contents of the pack and other information

Erbitux 5 mg/mL solution for infusion

cetuximab

Read this leaflet carefully before you use this medicine because it contains important
information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor.
If any side effects occur, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

• 1. What Erbitux is and what it is used for
• 2. What you need to know before you use Erbitux
• 3. How to use Erbitux
• 4. Possible side effects
• 5. How to store Erbitux
• 6. Contents of the pack and other 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
specifically recognize other certain proteins called antigens and bind to them.
Cetuximab binds to the epidermal growth factor receptor indicated with the acronym EGFR, which is an
antigen present on the surface of particular tumor cells. EGFR activates proteins called
RAS which play an important role in the complex signaling cascade that leads to the development and
progression of cancer (malignant tumor). As a result of this binding, the tumor cell
can no longer receive the messages necessary for growth, progression and the formation of metastases.

What is Erbitux used for
Erbitux is used for the treatment of two different types of cancer:
metastatic colorectal carcinoma. In these patients, Erbitux is used alone or in
combination with other cancer medicines.
a type of head and neck cancer (squamous cell carcinoma). In these patients,
Erbitux is used in combination with radiotherapy or with other cancer medicines.

2. What you need to know before using Erbitux

Do not use Erbitux
Do not use Erbitux if you have previously had a severe hypersensitivity (allergic) reaction to cetuximab.
Before starting treatment for metastatic colorectal cancer, your doctor will check if
tumor cells contain the normal (unmutated) or mutated form of RAS. You should not
receive Erbitux in combination with another cancer therapy containing oxaliplatin if your
tumor cells contain the mutated form of RAS.

Warnings and precautions
Consult your doctor before using Erbitux if any of the following information is not clear to you.
Erbitux may cause infusion-related reactions. These reactions may be of an allergic nature.
For more details, read “Infusion-related reactions” in section 4, as these reactions
can have serious consequences for you, including life-threatening conditions. These
side effects usually occur during the infusion, within 1 hour of administration, or
sometimes even later. To recognize the early signs of these reactions, your condition will be
regularly monitored during each Erbitux infusion and for at least one hour afterwards.
The likelihood of severe allergic reactions is higher if you are allergic to red meat or tick bites, or if you have had positive results for certain antibodies (found in a test). Your doctor
will discuss appropriate measures with you.
Erbitux may cause skin side effects. Your doctor will decide with you if you may
need certain preventive measures or early treatment. For more details,
also read “Skin side effects” in section 4, as some skin reactions
can have serious consequences, including life-threatening conditions.
If you have heart problems, your doctor will decide with you whether you can receive Erbitux in combination with
other anticancer drugs, especially if you are 65 years of age or older.
Erbitux may cause eye side effects. Consult your doctor if you have acute or worsening eye problems, such as blurred vision, eye pain, red and/or
very dry eyes, if you have had these problems in the past, or if you wear contact lenses. Your doctor will decide
with you if it is necessary to consult a specialist.
If you receive Erbitux in combination with cancer drugs, including platinum, you are more likely to
have a reduced number of white blood cells in your blood. Therefore, your doctor will monitor your blood and overall condition for any signs of infection (see also
“Side effects in combination with other cancer therapies” in section 4).
If you receive Erbitux in combination with other anticancer drugs, including fluoropyrimidines, it may
increase the likelihood of heart problems, which can be life-threatening. Your
doctor will discuss with you the possibility that you may need special supervision (see
also “Side effects in combination with other cancer therapies” in section 4).

Children and adolescents
There is no indication for specific use of Erbitux in children and adolescents.

Other medicines and Erbitux
Tell your doctor if you are taking, have recently taken, or might take any other
medicines, including those available without a prescription.

Pregnancy
Tell your doctor if you are pregnant or if you are not using reliable contraceptive methods (ask your doctor
if you are unsure). Your doctor will discuss the possible risks and benefits associated with the use of Erbitux in
these situations.

Breastfeeding
Do not breastfeed during the treatment period with Erbitux and for two months after the last dose.

Driving and operating machinery
Do not drive or use tools or machinery if you experience symptoms related to treatment that
affect your ability to concentrate and react.

3. How to use Erbitux

A doctor experienced in the use of anticancer drugs will monitor your therapy with Erbitux. During
each infusion and for at least one hour afterwards, your condition will be checked regularly to
verify if any early signs of infusion-related reactions appear.

Pretreatment
Before the first dose, you will receive an anti-allergic medication to reduce the risk of allergic
reactions. The doctor will decide whether such pretreatment is necessary for subsequent doses.

Dosage and method of administration
Erbitux is usually infused into a vein (administered as a drip). The doctor will calculate the correct 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 of

metastatic colorectal carcinoma:
The first dose (400 mg/m² of body surface area) is infused over a period of approximately 2 hours. Each subsequent
dose (250 mg/m² of body surface area) is infused over approximately 1 hour.

Every-two-week infusion for the treatment of squamous cell carcinoma of the head and

neck, when used in combination with other anticancer drugs, and metastatic colorectal carcinoma:

The dose of Erbitux (500 mg/m² of body surface area) is infused over approximately 2 hours.
Detailed instructions for the doctor or nurse on how to prepare the Erbitux infusion are

Duration of treatment
Erbitux is usually infused once a week. The duration of treatment may vary depending on
the disease you have and from person to person, therefore the doctor will discuss with you the duration of
therapy with Erbitux.

Combination with other cancer therapies
If you receive Erbitux in combination with other anticancer drugs, these drugs must be
administered at least one hour after the end of the Erbitux infusion.
If you receive Erbitux in combination with radiotherapy, treatment with Erbitux normally starts one
week before radiotherapy.
If you have any doubts about the use of this medicine, please consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The main side effects of Erbitux are infusion-related side effects and skin reactions:

Infusion-related side effects
More than 10 patients out of 100 are likely to experience infusion-related side effects; in
more than 1 patient out of 100 these reactions can be serious. These reactions may be of an
allergic nature. These side effects usually occur during the infusion, within 1 hour of
administration or sometimes even later.

Mild or moderate infusion-related side effectsinclude:
fever
chills
dizziness
difficulty breathing

If these symptoms occur, tell your doctor as soon as possible.To control these symptoms, the
doctor may decide to reduce the infusion rate of Erbitux.

Serious infusion-related side effectsinclude:
severe difficulty breathing, which occurs rapidly
hives
fainting
chest pain (a symptom of heart-related side effects)

If these symptoms occur, seek medical attention immediately.These side effects
can have serious consequences, including in rare cases conditions that have put the patient in
life-threatening danger and require immediate attention. Treatment with Erbitux must therefore be stopped.

Skin reactions
Skin reactions can occur in more than 80 patients out of 100. It is likely that in about
15 patients out of 100 these skin reactions are serious. Most of these effects occur
during the first three weeks of treatment. They usually disappear over time, after the end
of therapy with Erbitux.
The main skin reactions include:
skin changes similar to acne
itching
dry skin
scaling
excessive hair growth
nail changes, for example inflammation of the nail bed.
In very rare cases (may affect up to 1 in 10,000 people), patients may develop blisters or
skin peeling, which may indicate a serious skin reaction called “Stevens-Johnson syndrome”. If you
experience these symptoms, seek medical attention immediately,as these
signs can have serious consequences, including potentially fatal conditions.

If you notice the appearance of other extensive skin changes, tell your doctor as soon as
possiblebecause it may be necessary to change the dose of Erbitux or the interval between infusions. If skin
side effects recur after the dosage has been reduced several times, the doctor will decide whether to
stop treatment.

If you notice worsening of already affected skin areas, seek medical attention immediately,
especially in the presence of general signs of infection, such as fever and fatigue. These signs may
be indicative of a skin infection that can have serious consequences, including potentially fatal
conditions.

Lung reactions
In uncommon cases (may affect up to 1 in 100 people), patients may develop
inflammation of the lungs (called interstitial lung disease) which can have serious
consequences, including potentially fatal conditions.

If you notice symptoms such as the onset or worsening of difficulty breathing, consult
your doctor immediately, especially if you also have cough or fever. The doctor will decide whether to
stop treatment.

Other side effects

Very common side effects(may affect more than 1 in 10 people)
inflammation of the lining of the intestine, mouth and nose (sometimes severe), which in
some patients can cause nosebleeds
decreased levels of magnesium in the blood
increased levels of certain liver enzymes

Common side effects(may affect up to 1 in 10 people)
headache
fatigue
eye irritation and redness
diarrhoea
dehydration, which may be due to diarrhoea or reduced fluid intake
nausea
vomiting
loss of appetite with weight loss
decreased levels of calcium in the blood

Uncommon side effects(may 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 the front of the eye

Side effects of unknown frequency(frequency cannot be estimated on the basis of the available data

inflammation of the membranes surrounding the brain (aseptic meningitis)

Side effects in association with other cancer therapies
If you receive Erbitux in combination with other cancer medicines, some of the side effects
you may experience may also be related to the combination or the other medicines. If
you receive Erbitux in combination with cancer medicines, including platinum, you are more likely
to have a decrease in the number of white blood cells in the blood. This can cause infectious
complications, including life-threatening conditions, especially if you experience skin
reactions, inflammation of the lining of the intestine and mouth, or diarrhoea. Therefore, if
you notice general signs of infection, such as fever and fatigue, seek
medical attention immediately.
If you receive Erbitux in combination with a cancer medicine containing fluoropyrimidines, you are
more likely to experience the following side effects related to the other medicine:
chest pain
heart attack
heart failure
redness and swelling of the palms of the hands and soles of the feet, which can cause
skin cracking (hand-foot syndrome)
If you receive Erbitux in combination with radiotherapy, some of the side effects you may
experience may also be related to this combination, such as:
inflammation of the lining of the intestine and mouth
skin reactions typical of radiotherapy
difficulty swallowing
decreased number of white blood cells.

Reporting of side effects
If you get any side effects, talk to your doctor. You can also report side effects directly through
the national reporting system listed in Annex V. By reporting side effects you can help provide
more information on the safety of this medicine.

5. How to store Erbitux

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the packaging after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Once opened, Erbitux must be used immediately.

6. Contents of the pack and other information

What Erbitux contains
The active substance is cetuximab.
Each mL of solution for infusion contains 5 mg of cetuximab.
Each vial of 20 mL contains 100 mg of cetuximab.
Each vial of 100 mL contains 500 mg of cetuximab.
The other ingredients are: sodium chloride, glycine, polysorbate 80, citric acid monohydrate, sodium
hydroxide, water for injections.

Description of Erbitux and contents of the pack
Erbitux 5 mg/mL solution for infusion is supplied in vials containing 20 mL or 100 mL.
Each pack contains one vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Merck Europe B.V.
Gustav Mahlerplein 102
1082 MA Amsterdam
The Netherlands

Manufacturer
Merck Healthcare KGaA
Frankfurter Straße 250
64293 Darmstadt
Germany

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency, https://www.ema.europa.eu/ .
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The following information is intended exclusively for doctors or healthcare professionals:

Instructions for use
Erbitux can be administered by drip infusion, infusion pump or syringe pump.
Since Erbitux is compatible only with sterile sodium chloride 9 mg/mL injection solution (0.9%), it
must not be mixed with other medicines administered intravenously. For infusion, a separate infusion
line must be used, and the line must be flushed with a sterile sodium chloride 9 mg/mL (0.9%) injection
solution after 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 sets,
with polypropylene (PP) syringes for syringe pump.
Erbitux 5 mg/mL is chemically and physically stable for 48 hours at 25°C, if the solution is
prepared as described below. However, since it does not contain antimicrobial preservatives or
bacteriostatic agents, Erbitux must be used immediately. When preparing the infusion, care must be
taken to ensure aseptic handling. Erbitux 5 mg/mL should be prepared as follows:
For administration with an infusion pump or drip infusion (diluted with sterile sodium chloride 9 mg/mL
(0.9%) solution): take an infusion bag containing sterile sodium chloride 9 mg/mL (0.9%) solution, of
suitable volume. Calculate the required volume of Erbitux. Withdraw a suitable volume of sodium
chloride solution from the infusion bag using a sterile syringe and a suitable needle. Take a suitable
sterile syringe and insert a suitable needle. Draw up the required volume of Erbitux from a vial.
Transfer Erbitux into the previously prepared infusion bag. Repeat the procedure until the calculated
volume has been reached. Connect the infusion line, and fill the line with diluted Erbitux before
starting the infusion. Administer by drip infusion or an infusion pump.

Weekly infusion for the treatment of squamous cell carcinoma of the head and neck

and metastatic colorectal carcinoma:
The first 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 at an infusion rate of no more than 10 mg/min.

Infusion every two weeks for the treatment of squamous cell carcinoma of the head and

neck, when used in combination with other cancer medicines, and metastatic colorectal carcinoma:
The initial dose and subsequent doses (500 mg/m² of body surface area) are infused over approximately
2 hours at an infusion rate of no more than 10 mg/min.
For administration with an infusion pump or drip infusion (undiluted): calculate the
required volume of Erbitux. Take a suitable sterile syringe (minimum 50 mL) and insert a
suitable needle. Draw up the required volume of Erbitux from a vial. Transfer Erbitux into a
sterile container or bag. Repeat the procedure until the calculated volume
has been reached. Connect the infusion line and fill the line with Erbitux before starting
the infusion.

Weekly infusion for the treatment of squamous cell carcinoma of the head and neck

and metastatic colorectal carcinoma:
The first 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 at an infusion rate of no more than 10 mg/min.

Infusion every two weeks for the treatment of squamous cell carcinoma of the head and

neck, when used in combination with other cancer medicines, and metastatic colorectal carcinoma:
The initial dose and subsequent doses (500 mg/m² of body surface area) are infused over
approximately 2 hours at an infusion rate of no more than 10 mg/min.
For administration with a syringe pump: calculate the required volume of Erbitux. Take
a suitable sterile syringe and insert a suitable needle. Draw up the required volume of Erbitux from a
vial. Remove the needle and place the syringe in the syringe pump. Connect the infusion line to the
syringe after filling the line with Erbitux or with sterile sodium chloride 9 mg/mL (0.9%) solution. Repeat
this procedure until the calculated volume has been infused.

Weekly infusion for the treatment of squamous cell carcinoma of the head and neck

and metastatic colorectal carcinoma:
The first 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 at an infusion rate of no more than 10 mg/min.

Infusion every two weeks for the treatment of squamous cell carcinoma of the head and

neck, when used in combination with other cancer medicines, and metastatic colorectal carcinoma:
The initial dose and subsequent doses (500 mg/m² of body surface area) are infused over
approximately 2 hours at an infusion rate of no more than 10 mg/min.