Document: document 1 change

• document 0
• document 1
• document 2
• document 3
• document 4

---

PACKAGE LEAFLET: INFORMATION FOR THE USER IRINOTECAN 20 mg/ml Concentrate For Solution For Infusion

(irinotecan hydrochloride trihydrate)

What is in this leaflet:

1.    What Irinotecan 20 mg/ml is and what it is used for

2.    What you need to know before you take Irinotecan 20 mg/ml

3.    How take Irinotecan 20 mg/ml

4.    Possible side effects

5.    How to store Irinotecan 20 mg/ml

6.    Contents of the pack and other information

1. WHAT IRINOTECAN 20 mg/ml IS AND WHAT IT IS USED FOR

Your medicine is called Irinotecan.

Irinotecan 20 mg/ml belongs to a group of medicines called cytostatics (anti-cancer medicines).

Irinotecan may be used alone or in combination with a number of other medicines used to treat cancer. These combinations may be used to treat cancers of the large intestine (colon or rectum) where the disease is at an advanced stage.

Your doctor may use a combination of Irinotecan with 5-fluorouracil/folinic acid (5FU/FA) and bevacizumab to treat your cancer of the large intestine (colon or rectum).

Your doctor may use a combination of Irinotecan with capecitabine with or without bevacizumab to treat your cancer of the colon and rectum.

Your doctor may use a combination of Irinotecan with cetuximab to treat a particular type of cancer of the large intestine (KRAS wild-type) which expresses a protein called EGFR.

2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE IRINOTECAN 20 mg/ml Do not take Irinotecan:

•    if you are allergic to irinotecan or any other ingredient of this medicine (listed in section 6)

•    if you have or have had chronic inflammatory bowel disease or bowel obstruction;

•    if you are breast feeding;

•    if you have severe liver disease

•    if you have severe bone marrow failure;

•    if your general health status does not allow you to carry out general activities of daily living;

•    if you are taking St John’s Wort (a herbal supplement);

•    if you are taking a vaccine against yellow fever.

Warnings and precautions

Talk to your doctor before using Irinotecan:

•    If you have liver problems or jaundice

•    If you have kidney problems If you have asthma (asthma bronchial - lung disease)

•    If you have ever received radiation therapy

•    If you experienced severe diarrhoea or fever after being treated with Irinotecan before.

•    If you have heart problems

•    If you smoke, have high blood pressure or high cholesterol as these can increase the risk of heart problems during treatment with Irinotecan

•    If you have had or are due to have any vaccinations

•    If you are taking any other medicines. Please see the section below “Taking other medicines”.

As with all anti-cancer medicines the use of Irinotecan is associated with a number of side-effects which may be serious. These side-effects require special management to minimise the risk of complications.

You will be treated by a specialist team experienced in using these kinds of treatments and managing their side effects, which are usually temporary. However, it is essential that you read the section “POSSIBLE SIDE EFFECTS” and follow the instructions carefully if you get any of the symptoms described.

Others medicines and Irinotecan

Tell your doctor if you are taking , have recently taken or might take any other medicines.

If you receive Irinotecan in combination with either capecitabine, cetuximab or bevacizumab, please make sure that you also read the patient information leaflet for each medicine.

Some medicines, when taken at the same time as Irinotecan, may affect the way Irinotecan works or Irinotecan may affect the way they work. Tell your doctor if you are taking any of the following medicines:

•    St John’s Wort (a herbal supplement)

•    Ketoconazole (an antimycotic)

•    Rifampicin (an antiobiotic)

•    Carbamazepine (used to treat seizures)

•    Phenobarbital (used to treat seizures)

•    Phenytoin (used to treat epilepsy)

•    Warfarin (an anticoagulant used to thin the blood)

•    Atazanavir (used to treat HIV)

•    Ciclosporin or Tacrolimus (used to dampen down your body’s immune system)

If you go into hospital to have an operation, tell the anaesthetist and the medical staff that you are being treated with Irinotecan and any other medicines you are taking

Pregnancy, breast-feeding and fertility

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

If you become pregnant whilst being treated with Irinotecan you must inform your doctor immediately.

Both men and women should use effective contraception during treatment with Irinotecan and during up to 3 months after the treatment with irinotecan is finished.

Because Irinotecan may be harmful to nursing infants, women must not breast-feed while being treated with Irinotecan.

Driving and using machines

Irinotecan may make you feel dizzy or cause visual disturbances within 24 hours after administration of the product.

If this happens to you do not drive or operate machinery until this resolves.

Irinotecan contains sorbitol. If you have been told by your doctor that you have an intolerance to some sugars tell your doctor or nurse before you are given Irinotecan.

3. HOW TO USE IRINOTECAN 20 mg/ml

If you are prescribed Irinotecan it will only be given to you by doctors or nurses experienced in giving chemotherapy.

Method of administration

Irinotecan will be given as an infusion into your veins over a period of 30 to 90 minutes.

If you receive Irinotecan in combination with cetuximab, Irinotecan must not be administered earlier than 1 hour after the end of the cetuximab infusion.

Dosage and frequency of administration

The amount of Irinotecan you are given will depend on your age, size and general medical condition.

It will also depend on any other treatment you may have received for your cancer.

2

Your doctor will calculate your body surface area in square metres (m ).

•    If you have previously been treated with 5 fluorouracil you will normally be treated with

2

Irinotecan alone starting with a dose of 350 mg/m every three weeks.

2

•    If you have not had previous chemotherapy you will normally receive 180 mg/m Irinotecan every two weeks. This will be followed by folinic acid and 5-fluorouracil.

These dosages may be adjusted by your doctor depending on your condition and any side-effects you may have.

Duration of treatment

The number of infusions that you receive will depend on how you are responding to treatment. Your doctor will discuss this with you.

Blood Monitoring

Whilst you are taking Irinotecan and/or other similar medicines you will have regular blood tests to monitor your treatment and to ensure that there are no untoward adverse effects.

4. POSSIBLE SIDE EFFECTS

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

Your doctor will discuss these side-effects with you and explain the risks and benefits of your treatment.

Some of these side-effects must be treated IMMEDIATELY.

Please read the following instructions carefully and follow them if you have any of the side-effects listed.

Anaphylactic reactions (Rare side effects - Less than 1 in 1000 patients)

Anaphylactic reactions - severe allergic reaction may occur most often in the minutes following injection of the product: skin rash including red itchy skin, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing) and you may feel you are going to faint . If this happens you should tell your doctor IMMEDIATELY.

Allergic rections (Uncommon side effect - Less than 1 in 100 patients)

If you have wheeziness, difficulty in breathing, swelling, rash or itching (especially affecting the whole body) contact your doctor or nurse IMMEDIATELY.

Delayed diarrhoea (Very common side effects - more than 1 in 10 patients):

•    if your diarrhoea starts more than 24 hours after the infusion (“delayed diarrhoea”) you should IMMEDIATELY take any anti-diarrhoeal treatment that the doctor has given you EXACTLY as he has told you. If you are unsure of what this is, ask your doctor or nurse.

Drink large amounts of rehydration fluids, IMMEDIATELY (i.e. water, soda water, fizzy drinks, soup or oral rehydration therapy).

You must tell your doctor or pharmacist if you have any concerns.

•    you have nausea and vomiting as well as diarrhoea

•    you have any fever as well as the diarrhoea

•    you still have diarrhoea 48 hours after starting the diarrhoea treatment

Do not take any treatment for diarrhoea other than that given to you by your doctor or nurse and only drink the fluids described above.

Nausea and vomiting (Very common side effects - more than 1 in 10patients):

If you have nausea and/or vomiting contact your doctor or nurse IMMEDIATELY.

Neutropenia (decreased number of some white blood cells) Very common side effects - more than 1 in 10 patients):

Irinotecan may cause a decrease in the number of some of your white blood cells, which play an important role in fighting infections. This is called neutropenia.

Your doctor will probably arrange for you to have regular blood tests to monitor these white blood cells.

If you have any fever this may be an indication of infection associated with this neutropenia and requires immediate treatment.

If you have any fever, and particularly if you also have diarrhoea, contact your doctor or nurse IMMEDIATELY so that they can give you necessary treatment.

Acute cholinergic syndrome (Common side effects -less than 1 in 10patients):

the main symptoms are defined as early diarrhea and various other symptoms such as abdominal pain;

red, sore, itching or weeping eyes (conjunctivitis); running nose (rhinitis); low blood pressure;

widening of the blood vessels; sweating, chills; a feeling of general discomfort and illness; dizziness; visual disturbances, pupil contraction; watering eyes and increased salivation, occurring during or within the first 24 hours after the infusion of Irinotecan.

Tell your doctor or nurse about all your symptoms.

Do not use any anti-diarrhoeal treatment that your doctor has given you for “delayed diarrhoea” OTHER SIDE EFFECTS*

•    some of them need urgent medical aid; if you experience any of the following conditions please report it to a doctor or nurse IMMEDIATELY:

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

•    Blood disorders: anaemia.

•    Hair loss (the hair grows again after end of treatment).

•    In combination therapy transient serum levels of some enzymes (ALT, AST, alkaline phosphatase) or bilirubin

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

•    Fever associated with a severe decrease in the number of some white blood cells, thrombocytopenia (decreased number of blood platelets)

•    Dehydration, commonly associated with diarrhoea and /or vomiting.

•    Constipation.

•    Fatigue.

•    Increased levels of liver enzymes and creatinine in the blood

Uncommon side effects (may affect up to 1 in 100 people):

•    Mild skin reactions.

•    Early effects such as breathing difficulties.

•    Lung disease (interstitial pulmonary disease).

Rare side effects (may affect up to 1 in 1,000people):

•    Early effects such as muscular contraction or cramps and numbness (paraesthesia).

•    *Gastrointestinal bleeding and inflammation of the colon including the appendix.

•    *Intestinal perforation; Anorexia; *abdominal pain; inflammation of the mucous membranes.

•    inflammation of the pancreas.

•    Increased blood pressure during and following administration.

•    Decreased levels of potassium and sodium in the blood, mostly related to diarrhea and vomiting.

•    Abdominal pain and inflammation, causing diarrhoea (a condition known as pseudomembraneous colitis)

•    intestinal blockage.

•    infrequent cases of renal insufficiency, low blood pressure or cardio-circulatory failure have been observed in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting or sepsis.

•    Mild reactions at the infusion site

Very rare side effects (may affect up to 1 in 10,000people)

•    Transient speech disorders.

•    Increase in levels of some digestive enzymes which break down sugars and fats

If you receive Irinotecan in combination with cetuximab, some of the side effects you may experience can also be related to this combination. Such side effects may include an acne-like rash. Therefore, please make sure that you also read the package leaflet for cetuximab.

If you receive Irinotecan in combination with capecitabine, some of the side effects you may experience can also be related to this combination. Such side effects may include: very common blood clots, common allergic reactions, heart attack and fever in patients with a low white blood cell count. Therefore, please make sure that you also read the package leaflet for capecitabine.

If you receive Irinotecan in combination with capecitabine and bevacizumab, some of the side effects you may experience can also be related to this combination. Such side effects include: low white blood cell count, blood clots, high blood pressure and heart attack. Therefore, please make sure that you also read the package leaflet for capecitabine and bevacizumab.

If you get any side effects, talk to your doctor. This includes any side effects not listed in this leaflet.You can also report side effects directly via the national reporting system listed in via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE IRINOTECAN 20 mg/ml

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

Store below 25°C. Do not freeze.

Do not use this medicine after the expiry date which is stated on the vial and on the box after “EXP”. The expiry date refers to the last day of that month.

Keep the vial in the outer carton in order to protect from light.

Once the concentrate has been diluted for infusion the solution can be kept for 24 hours in a refrigerator (at 2 to 8°C).

6. CONTENTS OF THE PACK AND OTHER INFORMATION What Irinotecan 20 mg/ml contains:

-    The active substance is: irinotecan hydrochloride trihydrate.

Each vial of 2 ml contains 40 mg of irinotecan hydrochloride trihydrate, which is equivalent to 34.66 mg of irinotecan.

Each vial of 5 ml contains 100 mg of irinotecan hydrochloride trihydrate, which is equivalent to 86.65 mg of irinotecan.

Each vial of 15 ml contains 300 mg of irinotecan hydrochloride trihydrate, which is equivalent to 259.95 mg of irinotecan.

Each vial of 25 ml contains 500 mg of irinotecan hydrochloride trihydrate, which is equivalent to 433.25 mg of irinotecan.

1 ml of the concentrate for solution for infusion contains 20 mg of irinotecan hydrochloride trihydrate, which is equivalent to 17.33 mg of irinotecan.

-    The other ingredients are: sorbitol E420, lactic acid, sodium hydroxide (pH adjustment), water for injections.

What Irinotecan 20 mg/ml looks like and contents of the pack:

This medicine is in the form of a concentrate for solution for infusion. It is a clear solution.

Vials (type I amber glass) of 2 ml or 5 ml or 15 ml or 25 ml of solution with a chlorobutyl rubber stopper and cap (type flip off). Pack of 1, 5, 10 and 20 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Generics [UK] Ltd t/a Mylan, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom.

Manufacturer:

GP Pharm, Poligon Industrial Els Vinyets-Els Fogars, 08777 Sant Quinti de Mediona (Barcelona), SPAIN.

Or Mylan S.A.S., 117 allee des Parcs, 69800 Saint Priest, FRANCE.

Or Mylan B.V., 3752 LB Bunschoten, NETHERLANDS.

Or VIANEX S.A., Plant C, 16th Km. Marathonos Ave., 15351 Pallini Attiki, Athens, Greece This leaflet was last approved in October 2013.

f........................................................................................................................

.....^

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

Instructions for use / handling, preparation and disposal guide for use with Irinotecan

Concentrate for solution for infusion

USE/HANDLING

As with other antineoplastic agents, Irinotecan must be prepared and handled with caution. The use of glasses, masks and gloves is required.

If Irinotecan solution or infusion solution should come in contact with the skin, wash IMMEDIATELY and thoroughly with soap and water. If Irinotecan solution or infusion solution should come into contact with the mucous membranes, wash IMMEDIATELY with water.

Preparation for the intravenous solution

As with any other injectable drugs, the irinotecan solution must be prepared aseptically.

If any precipitate is observed in the vials or after dilution, the product should be discarded according to standard procedures for cytotoxic agents.

Do not use Irinotecan 20 mg/ml, if you notice any visible signs of deterioration.

Aseptically withdraw the required amount of Irinotecan solution from the vial with a calibrated syringe and inject into a 250 ml infusion bag or bottle containing either 0.9% sodium chloride or 5% glucose solution. The infusion should then be thoroughly mixed by manual rotation.

It is recommended, that in order to reduce microbiological hazard, the infusion solutions should be prepared immediately prior to use and infusion commenced as soon as practicable after preparation.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2 to 8°C unless dilution has taken place in controlled and validated aseptic conditions.

Irinotecan infusion should be infused into a peripheral or central vein.

Irinotecan should not be delivered as an intravenous bolus or an intravenous infusion shorter than 30 minutes or longer than 90 minutes.

Disposal

All materials used for dilution and administration should be disposed of according to hospital standard procedures applicable to cytotoxic agents.