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Irinotecan Hydrochloride 20 Mg/Ml Concentrate For Solution For Infusion

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Package leaflet: Information for the user

Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion

Irinotecan hydrochloride trihydrate

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

- Keep this leaflet. You may need to read it again.

- If you have any further questions, ask your doctor.

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Irinotecan is and what it is used for

2. What you need to know before you use Irinotecan

3. How Irinotecan will be given to you

4. Possible side effects

5. How to store Irinotecan

6. Contents of the pack and other information

1. What Irinotecan is and what it is used for

Irinotecan 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 cancer of the large intestine (KRAS wild-type) which expresses a protein called EGFR.

2. What you need to know before you use Irinotecan Do not use irinotecan if you

• are allergic to Irinotecan hydrochloride trihydrate or to any of the ingredients in this medicine (listed in section 6.)

• have or have had chronic inflammatory bowel disease or bowel obstruction

• are pregnant or breast-feeding or if you think you might be pregnant

• have severe liver disease

• have severe bone marrow failure

• are in poor general health which do not allow you to carry out general activities of daily living

• are taking St John’s Wort (depression herbal supplement)

• If you receive Irinotecan in combination with cetuximab, bevacizumab or capecitabine, please make sure that you also read the package insert for these products. These may contain other information you need to know before using these products.

Children

This medicine is intended for adults only. Check with your doctor if this medicine has been prescribed for use in a child

Warnings and precautions

Talk to your doctor before using Irinotecan.

Special care is needed for elderly patients.

Before treatment with Irinotecan tell your doctor if any of the following apply to you:

• You have liver problems or jaundice

• You have kidney problems

• You have asthma

• You have ever received radiation therapy

• You experienced severe diarrhoea or fever after being treated with Irinotecan Solution before

• You have heart problems

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

• You have had or are due to have any vaccinations

• You are taking any other medicines. Please see the section below “Other medicines and Irinotecan”.

As Irinotecan is an anti-cancer medicine it will be administered to you in a special unit and under the supervision of a doctor qualified in the use of anti-cancer medicines. The unit’s personnel will explain to you what you need to take special care of during and after the treatment. This leaflet may help you to remember that.

1. The first 24 hours after administration of Irinotecan

During administration of Irinotecan (30-90 min.) and shortly after administration you may experience some of the following symptoms:

• diarrhoea

• sweating

• abdominal pain

• watering eyes

• visual disturbance

• excessive mouth watering.

The medical term for these symptoms is “acute cholinergic syndrome” which can be treated (with atropine). If you have any of these symptoms immediately tell your doctor who will give you any treatment necessary.

2. From the day after treatment with Irinotecan until the next treatment

During this period you may experience various symptoms, which may be serious and require immediate treatment and close supervision.

Diarrhoea

If your diarrhoea starts more than 24 hours after administration of Irinotecan (“delayed diarrhoea”) it may be serious. It is often seen about 5 days after administration. The diarrhoea should be treated immediately and kept under close supervision. Immediately after the first liquid stools do the following:

1. Take any anti-diarrhoeal treatment that the doctor has given you exactly as he/she has told you. The treatment may not be changed without consulting the doctor. Recommended anti-diarrhoeal treatment is loperamide (4 mg for the first intake and then 2 mg every 2 hours, also during the night). This should be continued for at least 12 hours after the last liquid stools. The recommended dosage of loperamide may not be taken for more than 48 hours.

2. Drink large amounts of water and rehydration fluids immediately (such as water, soda water, fizzy drinks, soup or oral rehydration therapy).

3. Immediately inform your doctor who is supervising the treatment and tell him/her about the diarrhoea. If you are not able to reach the doctor, contact the unit at the hospital supervising the Irinotecan treatment. It is very important that they are aware of the diarrhoea.

You must immediately tell the doctor, or the unit supervising the treatment, if:

• you have diarrhoea as well as fever (over 38°C )

• you have severe diarrhoea (and vomiting) with excessive loss of water

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

Note: Do not take any treatment for diarrhoea other than that given to you by your doctor and the fluids described above. Follow the doctor’s instructions. The anti-diarrhoeal treatment should not be used to prevent a further episode of diarrhoea, even if you have experienced delayed diarrhoea at previous cycles.

Fever

If the body temperature increases over 38°C it may be a sign of infection, especially if you also have diarrhoea. If you have any fever (over 38°C) contact your doctor or the hospital unit immediately so that they can give you any treatment necessary.

Nausea and vomiting

If you have nausea and/or vomiting contact your doctor or the hospital; unit immediately

Neutropenia

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. Neutropenia is often seen during treatment with Irinotecan and is reversible. Your doctor should arrange for you to have regular blood tests to monitor these white blood cells. Neutropenia is serious and should be treated immediately and carefully monitored.

Breathing Difficulties

If you have any breathing difficulties contact your doctor immediately. Impaired Liver Function

Before treatment with Irinotecan is started and before every following treatment cycle the liver function should be monitored (by blood tests).

Impaired Kidney Function

As this medicine has not been tested in patients with kidney problems, please check with your doctor if you have any kidney problems.

If you have one or more of the symptoms mentioned, after you have returned home from the hospital, you should immediately contact the doctor or the hospital unit supervising the Irinotecan treatment.

Other medicines and Irinotecan

Tell your doctor or hospital pharmacist if you are taking, have recently taken or might take any other medicines including medicines obtained without a prescription. This is also valid for herbal medicines, strong vitamins and minerals.

Some medicines may alter the effect of Irinotecan. Tell your doctor if you are taking any of the following medicines:

• Ketoconazole (for the treatment of fungal infections)

• Rifampicin (for the treatment of tuberculosis)

• Carbamazepine, Phenobarbital or Phenytoin (for the treatment of epilepsy)

• Anticoagulant (used to thin the blood)

• Atazanavir (used to treat HIV)

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

• Vacdnes. Tell your doctor if you have had or are due to have any vaccinations. The herbal medicine St John’s Wort (Hypericum perforatum) must not be used during treatment with Irinotecan and not between treatments, as it may decrease the effect of Irinotecan.

If you require an operation, please tell your doctor or anaesthetist that you are using this medicine, as it may alter the effects of some medicines used during surgery.

Pregnancy, breast-feeding and fertility

Irinotecan must not be used during pregnancy. Women of child-bearing age should avoid becoming pregnant. Contraceptive measures must be taken by both male and female patients during and for at least three months after cessation of therapy. If you become pregnant during this period you must immediately inform your doctor.

Breast-feeding must be discontinued for the duration of Irinotecan therapy.

Driving and using machines

In some cases Irinotecan may cause side effects which affect the ability to drive and use tools and machines. Contact your doctor or pharmacist if you are unsure.

During the first 24 hours after administration of Irinotecan you may feel dizzy or have visual disturbances. If this happens to you do not drive or use any tools or machines.

Irinotecan contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’. This information may be of relevance to you if you are on a low sodium (salt) diet.

Irinotecan contains sorbitol.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How Irinotecan will be given to you

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

The amount of Irinotecan you will be given depends on your age, height, weight and general medical condition. It will also depend on any other treatment you may have received for your cancer. Your doctor will decide what is the right amount to use (the dose).

• If you have previously been treated with 5-fluorouracil, you will normally be treated with Irinotecan alone starting with a dose of 350 mg/m²every 3 weeks.

• If you have not had previous chemotherapy, you will normally receive 180 mg/m² Irinotecan every 2 weeks. This will be followed by folinic acid and 5-fluorouracil.

If you receive Irinotecan in combination with cetuximab, Irinotecan must not be administered earlier than one hour after the end of the cetuximab infusion. Please follow the advice of your doctor regarding your current treatment

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

If you use more Irinotecan than you should

Tell your doctor or care provider if you think that you have been given too much Irinotecan Solution. Acute overdosing worsens side effects like diarrhoea or neutropenia (a decrease in the number of white blood cells in the blood). Should this happen you will receive treatment to prevent dehydration. Your blood cell count will be monitored and any infections treated accordingly.

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. These are:

• diarrhoea

• a decrease in the number of neutrophil granulocytes, a type of white blood cell, which plays an important role in fighting infections.

• fever

• nausea and vomiting

• breathing difficulties (possible symptom of severe allergic reactions).

Please read instructions described in section “What you need to know before you use Irinotecan” carefully and follow them if you have any of the side effects listed above.

Other side effects include:

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

• Blood disorders including abnormally low number of neutrophil granulocytes, a type of white blood cell (neutropenia) and reduction of the quantity of haemoglobin in blood (anaemia)

• In combination therapy, thrombocytopenia (decreased number of blood platelets) causing bruises, tendency to bleed and abnormal bleeding

• In monotherapy, fever

• In monotherapy, infection

• Delayed severe diarrhoea

• In monotherapy, severe nausea (feeling sick) and vomiting (being sick)

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

• In combination therapy, transient and mild to moderate increase in serum levels of liver enzymes (SGPT, SGOT, alkaline phosphatase) or bilirubin.

Common side effects (less than 1 in 10 patients but more than 1 in 100):

• Severe transient acute cholinergic syndrome: the main symptoms are defined as early diarrhoea and various other symptoms such as abdominal pain; red, sore, itching or weeping eyes (conjunctivitis); running nose (rhinitis); low blood pressure; flushing due to widening of the blood vessels (vasodilation); 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

• In monotherapy, thrombocytopenia (reduction in the number of blood platelets) causing bruises, tendency to bleed and abnormal bleeding

• In combination therapy, fever

• In combination therapy, infection

• Infections associated with a severe decrease in the number of a certain type of white blood cells (neutropenia) resulting in death in 3 cases

• Fever associated with a severe decrease in the number of some white blood cells (febrile neutropenia)

• Loss of water (dehydration), commonly associated with diarrhoea and / or vomiting

• Constipation

• In combination therapy, severe nausea (feeling sick) and vomiting (being sick)

• In combination therapy, transient severe increase in serum levels of bilirubin

• Feeling weak (asthenia)

• In monotherapy, transient and mild to moderate increase in serum levels of some liver enzymes (transaminases, alkaline phosphatase) or bilirubin

• Transient and mild to moderate increase in serum levels of creatinine in the blood

• In combination therapy, transient pronounced (grade 3) increase in serum levels of bilirubin.

Uncommon side effects (less than 1 in 100 patients but more than 1 in 1000):

• Mild allergic reactions (skin rash including red itchy skin, urticaria, conjunctivitis and rhinitis)

• Mild skin reactions; mild reactions at the infusion site

• Lung disease presenting as shortness of breath, dry cough and inspiratory crackles (interstitial pulmonary disease); early effects such as breathing difficulties

• Partial or complete blockage of the bowel (intestinal obstruction, ileus), stomach and intestines bleeding

• Bowel inflammation causing abdominal pain and/or diarrhoea (a condition known as pseudomembranous colitis)

• Renal insufficiency, low blood pressure or cardio-circulatory failure in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or sepsis.

Rare side effects (less than 1 in 1,000 patients but more thanl in10,000):

• severe allergic reactions (anaphylatic/anaphylactoid reaction), including swelling of the of the hands, feet, ankles, face, lips, mouth or throat which may cause difficulty in swallowing or extreme difficulty in breathing

• Muscular contraction or cramps, and numbness (paraesthesia)

• Inflammation of the large bowel causing abdominal pain (colitis including typhlitis, ischemic and ulcerative colitis)

• Intestinal perforation

• Loss of appetite (anorexia)

• Abdominal pain

• Inflammation of the mucous membranes

• Symptomatic or asymptomatic inflammation of the pancreas (mainly abdominal pain)

• Increased blood pressure during and following administration

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

Very rare side effects (less than 1 in 10,000 patients)

• One case of low platelet count in the blood due to antibodies against platelets

• Transient speech disorders

• Increase in levels of some digestive enzymes which break down sugars (amylase) and fats (lipase).

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.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via:

Yellow Card Scheme

Website: www.mhra.aov.uk/vellowcard.

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

5. How to store Irinotecan

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 vial label and outer carton 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.

For single use only.

Do not freeze.

From a microbiological point of view, the solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C unless dilution has taken place in controlled and validated aseptic conditions.

Your doctor must use the Irinotecan as soon as it has been made.

Vials that have already been used must be disposed of by your healthcare professional according to hospital standard procedures applicable to cytotoxic medicines.

6. Contents of the pack and other information What Irinotecan contains

• The active substance is Irinotecan. One ml of concentrate contains 20 mg Irinotecan hydrochloride trihydrate equivalent to 17.33 mg/ml Irinotecan. Each 2 ml, 5 ml, 15 ml or 25 ml vial of Irinotecan contains 40 mg, 100 mg, 300 mg, and 500 mg of Irinotecan hydrochloride trihydrate respectively

• The other ingredients are sorbitol E420, lactic acid, water for injection and sodium hydroxide, hydrochloric acid (used to adjust the pH).

What Irinotecan looks like and contents of the pack

This medicine is in the form of a concentrate for solution for infusion (a concentrated solution which is diluted to make a solution that can be given as a slow infusion via a drip). It is a clear yellow solution. The medicine comes in amber colour glass containers called vials and are available as single vials containing 40mg/2ml, 100mg/5ml, 300mg/15ml or 500mg/25ml. These vials are for single use only.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Seacross Pharmaceuticals Limited,

Bedford Business Centre,

61-63 St Peters Street,

Bedford MK40 2PR,

United Kingdom

Manufacturer

GP Pharm, S.A

Poliogono Industrial Els, Vinyets-Els Fogars,

2, Ctra. C-244, Km. 22, 08777 Sant Quanti de Mediona (Barcelona), Spain

This medicinal product is authorised in the Member States of the EEA under the following names:

This leaflet was last revised in 05/2015

UK	Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion
SE	Irinotecan Seacross 20 mg/ml koncentrat till infusionsvatska, losning
NO	Irinotecan Seacross 20 mg/ml konsentrat til infusjonsvaeske
DK	Irinotecan Seacross
LT	Irinotecan Seacross 20 mg/ml koncentratas infuziniam tirpalui
EE	Irinotecan Seacross 20 mg/ml
FI	Irinotecan Seacross 20 mg/ml infuusiokonsentraatti, liuosta varten

INFORMATION FOR HEALTHCARE PROFESSIONALS

Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion Irinotecan hydrochloride trihydrate

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

Instructions for use - cytotoxic

Handling of Irinotecan

As with all other antineoplastic agents, caution should be exercised when handling Irinotecan. Dilution should be carried out under aseptic conditions by trained personnel in a designated area. Precautions should be taken to avoid contact with the skin and mucous membranes.

Protection instructions for preparation of Irinotecan for infusion

1. Protective chamber should be used and protective gloves as well as protective gown should be worn. If there is no protective chamber available mouth cover and goggles should be used.

2. Opened containers, like injection vials and infusion bottles and used cannulae, syringes, catheters, tubes, and residuals of cytostatics should be considered as hazardous waste and undergo disposal according to local guidelines for the handling of HAZARDOUS WASTE.

3. Follow the instructions below in case of spillage:

• protective clothing should be worn

• broken glass should be collected and placed in the container for HAZARDOUS WASTE

• contaminated surfaces should be flushed properly with copious amounts of cold water

• the flushed surfaces should then be wiped thoroughly and the materials used for wiping should be disposed of as HAZARDOUS WASTE.

4. In the event of Irinotecan contact with the skin, the area should be rinsed with plenty of running water and then washed with soap and water. In case of contact with mucous membranes, wash the contacted area thoroughly with water. If you have any discomfort, contact a doctor.

5. In case of contact of Irinotecan with eyes, wash them thoroughly with plenty of water. Contact an ophthalmologist immediately.

Preparation of the infusion solution

Irinotecan is intended for intravenous infusion only after diluting prior to administration in the recommended diluents, either 0.9 % sodium chloride solution for infusion or 5% glucose solution for infusion. Aseptically withdraw the required amount of Irinotecan concentrate for solution from the vial with a calibrated syringe and inject into a 250 ml infusion bag or bottle. The infusion should be thoroughly mixed by manual rotation.

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

This medicinal product must not be mixed with other medicinal products except those mentioned above.

Irinotecan solution for 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. After dilution: the solution should be used immediately as it contains no antibacterial preservative. If reconstitution and dilution are performed under strict aseptic conditions (e.g. on Laminar Air Flow bench) the solution should be used (infusion completed) immediately or within 24 hours if stored at 2° C - 8°C after the first opening.

Disposal

All items used for preparation, administration or otherwise coming into contact with Irinotecan should undergo disposal according to local guidelines for the handling of cytotoxic compounds.

Package leaflet: Information for the user

Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion

Irinotecan hydrochloride trihydrate

101020 025018

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

- Keep this leaflet. You may need to read it again.

- If you have any further questions, ask your doctor.

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Irinotecan is and what it is used for

2. What you need to know before you use Irinotecan

3. How irinotecan will be given to you

4. Possible side effects

5. How to store Irinotecan

6. Contents of the pack and other information

1. What Irinotecan is and what it is used for

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 cancer of the large intestine (KRAS wild-type) which expresses a protein called EGFR.

2. What you need to know before you use Irinotecan Do not use Irinotecan if you

• are allergic to Irinotecan hydrochloride trihydrate or to any of the ingredients in this medicine (listed in section 6.)

• have or have had chronic inflammatory bowel disease or bowel obstruction

• are pregnant or breast-feeding or if you think you might be pregnant

• have severe liver disease

• have severe bone marrow failure

• are in poor general health which do not allow you to carry out general activities of daily living

• are taking St John’s Wort (depression herbal supplement)

Children

This medicine is intended for adults only. Check with your doctor if this medicine has been prescribed for use in a child

Warnings and precautions

Talk to your doctor before using Irinotecan.

Special care is needed for elderly patients.

Before treatment with Irinotecan tell your doctor if any of the following apply to you:

• You have liver problems or jaundice

• You have kidney problems

• You have asthma

• You have ever received radiation therapy

• You experienced severe diarrhoea or fever after be ng treated with Irinotecan Solution before

• You have heart problems

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

• You have had or are due to have any vaccinations

• You are taking any other medicines. Please see the section below “Other medicines and Irinotecan”.

1. The first 24 hours after administration of Irinotecan

During administration of Irinotecan (30-90 min.) and shortly after administration you may experience some of the following symptoms:

• diarrhoea

• sweating

• abdominal pain

• watering eyes

• visual disturbance

• excessive mouth watering.

The medical term for these symptoms is “acute cholinergic syndrome" which can be treated (with atropine). If you have any of these symptoms immediately tell your doctor who will give you any treatment necessary.

2. From the day after treatment with Irinotecan until the next treatment

During this period you may experience various symptoms, which may be serious and require immediate treatment and close supervision.

Diarrhoea

If your diarrhoea starts more than 24 hours after administration of Irinotecan (“delayed diarrhoea") it may be serious. It is often seen about 5 days after administration. The diarrhoea should be treated immediately and kept under close supervision. Immediately after the first liquid stools do the following:

2. Drink large amounts of water and rehydration fluids immediately (such as water, soda water, fizzy drinks, soup or oral rehydration therapy).

You must immediately tell the doctor, or the unit supervising the treatment, if:

• you have diarrhoea as well as fever (over 38°C )

• you have severe diarrhoea (and vomiting) with excessive loss of water

• you still have diarrhoea 48 hoursafter starting the diarrhoea treatment.

Note: Do not take any treatment fcr diarrhoea other than that given to you by your doctor and the fluids described above. Follow the doctor's instructions. The anti-diarrhoeal treatment should not be used to prevent a further episode of diarrhoea, even if you have experienced delayed diarrhoea at previous cycles.

Fever

Nausea and vomiting

If you have nausea and/or vomiting contact your doctor or the hospital unit immediately

Neutropenia

Irinotecan may cause a decrease in Ihe number of some of your white blood cells, which play an important role in fighting infections. This is called neutropenia. Neutropenia is often seen during treatment with Irinotecan and is reversible. Your doctor should arrange for you to have regular blood tests to monitor these white blood cells. Neutropenia is serious and should be treated immediately and carefully monitored.

Breathing Difficulties

If you have any breathing difficulties contact your doctor immediately. Impaired Liver Function

Before treatment with Irinotecan is started and before every following treatment cycle the liver function should be monitored (by blood tests).

Impaired Kidney Function

As this medicine has not been tested in patients with kidney problems, please check with your doctor if you have any kidney problems.

If you have one or more of the symptoms mentioned, after you have returned home from the hospital, you should immediately contact the doctor or the hospital unit supervising the Irinotecan treatment.

Other medicines and Irinotecan

Some medicines may alter the effect of Irinotecan. Tell your doctor if you are taking any of the following mecicines:

• Ketoconazole (for the treatment of fungal infections)

• Rifampicin (for the treatment of :uberculosis)

• Carbamazepine, Phenobarbital or Phenytoin (for the treatment of epilepsy)

• Anticoagulant (used to thin the blood)

• Atazanavir (used to treat HIV)

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

• Vacdnes. Tell your dodor if you have had or are due to have any vacdnations. The herbal medicine St John’s Wort {Hypericum perforatum) must not be used during treatment with Irinotecan and not between treatments, as it may decrease the effect of Irinotecan.

If you require an operation, please tell your doctor or anaesthetist that you are using this medicine, as it may alter the effects of some medicines used during surgery.

Pregnancy, breast-feeding and fertility

Breast-feeding must be discontinued for the duration of Irinotecan therapy.

Driving and using machines

In some cases Irinotecan may cause side effects which affect the ability to drive and use tools and machines. Contact your doctor or pharmacist if you are unsure.

During the first 24 hours after adm nistration of Irinotecan you may feel dizzy or have visual disturbances. If this happens to you do not drive or use any tools or machines.

Irinotecan contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.This information may be of relevance to you if you are on a low sodium (salt) diet.

Irinotecan contains sorbitol.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How Irinotecan will be given to you

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

The amount of Irinotecan you will be given depends on your age, height, weight and general medical condit on. It will also depend on any other treatment you may have received for your cancer. Your doctor will decide what is the right amount to use (the dose).

• If you have previously been treated with 5-fluorouracil, you will normally be treated with Irinotecan alone starting with a dose of 350 mg/m²every 3 weeks.

• If you have not had previous chemotherapy, you will normally receive 180 mg/m² Irinotecan every 2 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.

If you use more Irinotecan than you should

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. These are:

• diarrhoea

• a decrease in the number of neutrophil granulocytes, a type of white blood cell, which plays an important role in fighting infections.

• fever

• nausea and vomiting

• breathing difficulties (possible symptom of severe allergic reactions).

Please read instructions described in section “What you need to know before you use Irinotecan" carefully and follow them if you have any of the side effects listed above.

Other side effects include:

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

• Blood disorders including abnormally low number of neutrophil granulocytes, a type of white blood cell (neutropenia) and reduction of the quantity of haemoglobin in blood (anaemia)

• In combination therapy, thrombocytopenia (decreased number of blood platelets) causing bruises, tendency to bleed and abnormal bleeding

• In monotherapy, fever

• In monotherapy, infection

• Delayed severe diarrhoea

• In monotherapy, severe nausea (feeling sick) and vomiting (being sick)

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

• In combination therapy, transient and mild to moderate increase in serum levels of liver enzymes (SGPT, SGOT, alkaline phosphatase) or bilirubin.

Common side effects (less than 1 in 10 patients but more than 1 in 100):

• In monotherapy, thrombocytopenia (reduction in the number of blood platelets) causing bruises, tendency to bleed and abnormal bleeding

• In combination therapy, fever

• In combination therapy, infection

• Infections associated with a severe decrease in the number of a certain type of white blood cells (neutropenia) resulting in death in 3 cases

• Fever associated with a severe decrease in the number of some white blood cells (febrile neutropenia)

• Loss of water (dehydration), commonly associated with diarrhoea and / or vomiting

• Constipation

• In combination therapy, severe nausea (feeling sick) and vomiting (being sick)

• In combination therapy, transient severe increase in serum levels of bilirubin

• Feeling weak (asthenia)

• In monotherapy, transient and mild to moderate increase in serum levels of some I ver enzymes (transaminases, alkaline phosphatase) or bilirubin

• Transient and mild to moderate increase in serum levels of creatinine in the blood

• In combination therapy, transient pronounced (grade 3) increase in serum levels of bilirubin.

Uncommon side effects (less than 1 in 100 patients but more than 1 in 1000):

• Mild allergic reactions (skin rash including red itchy skin, urticaria, conjunctivitis and rhinitis)

• Mild skin reactions; mild reactions at the infusion site

• Lung disease presenting as shortness of breath, dry cough and inspiratory crackles (interstitial pulmonary disease); early effects such as breathing difficulties

• Partial or complete blockage of the bowel (intestinal obstruction, ileus), stomach and intestines bleeding

• Bowel inflammation causing abdominal pain and/or diarrhoea (a condition known as pseudomembranous colitis)

• Renal insufficiency, low blood pressure or cardio-circulatory failure in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or sepsis.

Rare side effects (less than 1 in 1,000 patients but more than 1 in 10,000):

• Muscular contraction or cramps, and numbness (paraesthesia)

• Inflammation of the large bowel causing abdominal pain (colitis including typhlitis, ischemic and ulcerative colitis)

• Intestinal perforation

• Loss of appetite (anorexia)

• Abdominal pain

• Inflammation of the mucous membranes

• Symptomatic or asymptomatic inflammation of the pancreas (mainly abdominal pain)

• Increased blood pressure during and following administration

• Decreased levels of potassium and sodium in the b ood, mostly related to diarrhoea and vomiting.

Very rare side effects (less than 1 in 10,000 patients)

• One case of low platelet count in the blood due to antibodies against platelets

• Transient speech disorders

• Increase in levels of some digestive enzymes which break down sugars (amylase) and fats (lipase).

If you receive Irinotecan in combination with cetuximab, some of the side effects you may experience can also be related to th s combination.

Such side effects may include an acne-like rash. Therefore, please make sure that you also read the package leaflet for cetuximab.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via:

Yellow Card Scheme

Website: www.mhra.aov.uk/vellowcard.

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

5. How to store Irinotecan

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 vial label and outer carton after EXR The expiry date refers to the last day of that month.

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

For single use only.

Do not freeze.

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

Your doctor must use the Irinotecan as soon as it has been made.

Vials that have already been used must be disposed of by your healthcare professional according to hospital standard procedures applicable to cytotoxic medicines.

6. Contents of the pack and other information What Irinotecan contains

• The other ingredients are sorbitol E420, lactic acic, water for injection and sodium hydroxide, hydrochloric acid (used to adjust the pH).

What Irinotecan looks like and contents of the pack

This medicine is in the form of a concentrate for solution for infusion (a concentrated solution which is diluted to make a soUtion that can be given as a slow infusion via a drip). It is a clear yellcw solution. The medicine comes in amber colour glass containers called vials and are available as single vials containing 40mg/2ml, 100mg/5ml, 300mg/15ml or 500mg/25ml. These vials are for single use only.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Seacross Pharmaceuticals Limited,

Bedford Business Centre,

61-63 St Peters Street,

Bedford MK40 2PR,

United Kingdom

Manufacturer

Pharmaceutical Solutions Ltd KW20 Korradino Industrial Estate Paola Pla 3000 Malta

This medicinal product is authorised in the Member States of the EEA under the following names:

UK	Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion
SE	Irinotecan Seacross 20 mg/ml koncentrat till infusionsvatska, losning
NO	Irinotecan Seacross 20 mg/ml konsentrat til infusjonsvaeske
DK	Irinotecan Seacross
LT	Irinotecan Seacross 20 mg/ml koncentratas infuziniam tirpalui
EE	Irinotecan Seacross 20 mg/ml
FI	Irinotecan Seacross 20 mg/ml infuusiokonsentraatti, liuosta varten

This leaflet was last revised in 05/2015

INFORMATION FOR HEALTHCARE PROFESSIONALS

Irinotecan hydrochloride 20 mg/ml concentrate for solution for infusion Irinotecan hydrochloride trihydrate

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

Instructions for use - cytotoxic

Handling of Irinotecan

Protection instructions for preparation of Irinotecan for infusion

1. Protective chamber should be used and protective gloves as well as protective gown should be worn. If there is no protective chamber available mouth cover and goggles should be used.

3. Follow the instructions below in case of spillage:

• protective clothing should be wan

• broken glass should be collected and placed in the container for HAZARDOUS WASTE

• contaminated surfaces should be flushed properly with copious amounts of cold water

• the flushed surfaces should then be wiped thoroughly and the materials used for wiping should be disposed of as HAZARDOUS WASTE.

5. In case of contact of Irinotecan with eyes, wash them thoroughly with plenty of water. Contact an ophthalmologist immediately.

Preparation of the infusion solution

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

This medicinal product must not be mixed with othermedicinal products except those mentioned above.

Irinotecan solution for 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 longsr than 90 minutes. After dilution: the solution should be used immediately as it contains no antibacterial preservative. If reconstitution and dilution are performed under strict aseptic conditions (e.g. on Laminar Air F.ow bench) the solution should be used (infusion completed) immediately or within 24 hours if stored at 2° C - 8°C after the first opening.

Disposel

All items used for preparation, administration or otherwise coming into contact with Irinotecan should undergo disposal according to local guidelines for the handling of cytotoxic compounds.