Cetomedica 20 mg/ml concentraat voor oplossing voor infusie

Cetomedica belongs to a group of medicines called cytostatics (anti-cancer medicines).

It is used for the treatment of advanced cancer of colon and rectum in adults, either in combination with other medicines (i.e. 5-fluorouracli/folinic acid, bevacizumab, cetuximab, capecitabine) or alone.

Do not use Cetomedica

• if you are allergic (hypersensitive) to irinotecan hydrochloride trihydrate or any of the other ingredients of Cetomedica Solutioin;
• if you have any other bowel disease or a history of bowel obstruction;
• if you are breast-feeding (see “Pregnancy and breast-feeding”);
• if you have high levels of bilirubin (a waste blood product) in the blood (more than 3 times the upper limit of normal);
• if you have an imbalance of your blood cells (severe bone marrow failure);
• if you are in a poor general health (evaluated by an international standard);
• if you are using the natural remedy St John´s wort (Hypericum perforatum).

If you receive Cetomedica in combination with cetuximab or bevacizumab or capecitabine, please make sure that you also read the package leaflet for these medicines. The combination could lead to additional contraindications.

Take special care with Cetomedica

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

Elderly patients require more intense surveillance during treatment.

As Cetomedica is an anti-cancer medicine it will be administered to you in a special unit and under supervision of a doctor qualified in the use of anti-cancer medicines. The units’ 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.

If you receive Cetomedica in combination with cetuximab or bevacizumab or capecitabine, please make sure that you also read the package leaflet for these medicinal products.

In the first 24 hours after administration of Cetomedica

During administration of Cetomedica Solution (30 – 90 minutes) and within 24 hours 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”. If you have any of these symptoms, immediately tell your doctor who will give you any treatment necessary.

From the day after treatment with Cetomedica until 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 Cetomedica (“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 antidiarrhoeal treatment that the doctor has given you, exactly as he/she has told you. The treatment must not be changed without consulting the doctor.
2. Drink large amounts of water and rehydration fluids, immediately (i.e. 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 hospital unit supervising the Cetomedica 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 requiring intravenous hydration
• 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 antidiarrhoeal treatment should not be used preventive, even though you have experienced delayed diarrhoea at previous cycles.

Nausea and vomiting

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

Neutropenia

Cetomedica 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 Cetomedica and is reversible. Your doctor should arrange for you to have regular blood tests to monitor these white blood cells. If you have any fever (over 38°C) this may be an indication of infection associated with this neutropenia and requires immediate treatment. Therefore, if you have any fever, and particularly if you also have diarrhoea, contact your doctor or nurse immediately, that they can give you the necessary treatment.

Breathing difficulties

If you have any breathing difficulties contact your doctor immediately.

Impaired liver function

Before treatment with Cetomedica is started and before every following treatment cycle your doctor will monitor your liver function (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.

Heart problems

If you are at risk of having a heart attack your doctor should monitor you very carefully while you are given Cetomedica and action should be taken to minimize the risk factors (e.g. smoking, high blood pressure, high levels of blood lipids).

Lowered resistance to Infections

Vaccination with a live or life-attenuated vaccine is not recommended in patients receiving Cetomedica, because this might result in serious or fatal infections. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

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

Taking other medicines

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

The following medications can alter the effects of Cetomedica:

• carbamazepine, phenobarbital or phenytoin (medicines for the treatment of epilepsy)
• ketoconazole (used to treat fungal infections)
• rifampicin (used for the treatment of tuberculosis)
• atazanavir sulphate (used to treat HIV infection)
• the herbal medicine St John’s Wort (Hypericum perforatum, a treatment for depression. This must not be used during and between treatments with Cetomedica, as it may decrease the effect of Cetomedica.
• Oral anticoagulants (used to reduce blood clotting)
• Yellow fever vaccine (must not be used while you are treated with Cetomedica)
• Other live attenuated vaccines are also not recommended (see section “Take special care with Cetomedica”, chapter “Lowered resistance to Infections”).
• Ciclosporine and Tacrolimus (both used to reduce the activity of the immune system, e.g. after organ transplant)

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

Pregnancy and breast-feeding

You should not be given Cetomedica if you are pregnant unless clearly indicated by your doctor.

Women of child-bearing age should avoid becoming pregnant.

Contraceptive measures must be taken by both male and female patients of reproductive age during and for at least three months after cessation of therapy.

Still, if you become pregnant during this period you must immediately inform your doctor.

It is not known whether Cetomedica is excreted in human milk.

Consequently you must not breast-feed while you are treated with Cetomedica.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

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

This medicine may also cause other side effects which affect your ability to drive and use tools and machines. Contact your doctor or pharmacist if you are unsure.

Important information about some of the ingredients of Cetomedica Solution

Cetomedica Solution 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.

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium-free’.

Cetomedica will be given to you by a doctor or nurse, the solution is infused into the vein (as a drip). Cetomedica is for adults only.

Dosage

The amount of infusion you are given will depend on your age, size, weight and general medical condition. It will also depend on any other treatment you may have received for your cancer. Your doctor will calculate your body surface area in square metres (m2).

If you have been treated before, when used alone, you receive an infusion of 350 mg/m2 over a 30 to 90 minute period every three weeks.

If you have not been treated before you receive an infusion of 180 mg/m2 over a 30 to 90 minute period once every two weeks. Each treatment is followed by an infusion with folinic acid and 5-fluorouracil (other cancer treatments).

If you receive Cetomedica in combination with cetuximab, Cetomedica must not be administered earlier than 1 hour after the end of the cetuximab infusion. Please follow the advice if your doctor regarding your current treatment.

If you receive Cetomedica in combination with bevacizumab, please consult the bevacizumab leaflet.

If you receive Cetomedica in combination with capecitabine, please consult the capecitabine leaflet.

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

The dose should be chosen carefully in elderly patients and more intense surveillance is required. Cetomedica is not recommended for patients with kidney disorders.

Please tell your doctor if you have a genetic disorder with a reduced activity of the enzyme UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1).

Duration of treatment

Treatment is continued as long as possible. If the cancer gets worse or the side effects are unacceptable, the treatment will be stopped.

If you receive more Cetomedica than you should

Cetomedica will be given to you by a doctor or nurse who is familiar with this type of treatment so the chance is very small to be given an overdose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Cetomedica 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 (see also information in section “Take special care with Cetomedica”).

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

• Blood disorders:
  • Decreased number of a certain type of white blood cells (neutropenia) which increases the risk of infections.
  • Decrease number of red blood cells (anaemia) which can make the skin pale and cause weakness and breathlessness.
  • Decreased number of blood platelets (thrombocytopenia) which increases the risk of bruising and bleeding (in combination therapy).
• Fever and infections (in monotherapy).
• Delayed severe diarrhoea.
• Severe nausea and vomiting (in monotherapy).
• Hair loss (the hair grows again after end of treatment).
• Transient and mild to moderate increase in serum levels of some liver enzymes (AST, ALT, alkaline phosphate) or bilirubin (in combination therapy).

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; 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 Cetomedica.
• Decreased number of blood platelets (thrombocytopenia) which increases the risk of bruising and bleeding (in monotherapy).
• Fever and infections (in combination therapy).
• 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 a certain type of white blood cells (febrile neutropenia).
• Severe nausea and vomiting (in combination therapy).
• Loss of water (dehydration), commonly associated with diarrhoea and /or vomiting.
• Constipation.
• Severe weakness (asthenia).
• Transient and mild to moderate increase in serum levels of some liver enzymes (transaminases, alkaline phosphatase) or bilirubin (in monotherapy).
• Transient and mild to moderate increase of creatinine in the blood.
• Transient severe (grade 3) increase in serum levels of bilirubin (in combination therapy).

Uncommon side effects (less than 1 in 100 patients but more than 1 in 1,000)

• Mild allergic reaction (skin rash including red itchy skin, urticaria, conjunctivitis, 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 blockage, ileus).
• Stomach and intestines bleeding.
• Bowel inflammation which causes abdominal pain and/or diarrhoea (a condition known as pseudo- membraneous colitis).
• Kidney problems (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.

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

• Severe allergic reactions causing swelling of the hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing (anaphylatic/ anaphylactoid reaction).
• 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.
• Inflammation of the pancreas (pancreatitis) which may cause 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 effects (less than 1 in 10,000 patients)

• Bruising or bleeding easily due to your body destroying its own blood platelets (peripheral thrombocytopenia with antiplatelet antibodies [one case]).
• Temporary speech disorders.
• Increase in levels of some digestive enzymes which break down sugars and fats.

Side effects resulting from the combination with other medicines

If you receive Cetomedica in combination with certain other medicines, some of the side effects you may experience can also be related to this combination.

Cetomedica in combination with:

• Cetuximab: an acne-like rash.
• Capecitabine: formation/presence of blood clots, obstruction/occlusion of a blood vessel by a blood clot (very common), severe allergic reactions, insufficient blood flow to the heart muscle often resulting in chest pain (cardiac ischemia), heart attack and fever associated with a severe decrease in the number of a certain type of white blood cells (febrile neutropenia) (common).
• Capecitabine and bevacizumab: decrease in the number of a certain type of white blood cells (neutropenia), formation/presence of blood clots, obstruction/occlusion of a blood vessel by a blood clot (embolism), high blood pressure, insufficient blood flow to the heart muscle often resulting in chest pain (cardiac ischemia) and heart attack. These side effects are common.

Please make sure that you also read the package leaflet for these medicines.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Do not refrigerate or freeze.

Keep the vial in the outer carton in order to protect from light. Keep out of the reach and sight of children.

Do not use Cetomedica Solution 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 the month.

For single use only.

The infusion solution should be prepared immediately prior to use and infusion commenced as soon as practicable after preparations.

What Cetomedica Solution contains

• The active substance is irinotecan hydrochloride trihydrate. Each ml of the concentrate contains 20 mg irinotecan hydrochloride trihydrate equivalent to 17.33 mg irinotecan. Each vial with 2 ml of the concentrate contains 40 mg irinotecan hydrochloride trihydrate. Each vial with 5 ml of the concentrate contains 100 mg irinotecan hydrochloride trihydrate.
• The other ingredients are sorbitol (E420), lactic acid (E270), sodium hydroxide (E524), hydrochloric acid (E507) and water for injection.

What Cetomedica Solution looks like and contents of the pack

Cetomedica concentrate for solution for infusion is a pale yellow, clear aqueous solution.

Cetomedica 40 mg/2 ml and 100 mg/5 ml are available in boxes containing one single amber glass vial. Pack sizes:

One vial of 2 ml/pack

One vial of 5 ml/pack

Marketing Authorisation Holder and Manufacturer

Regiomedica GmbH

Teichstr. 66

79539 Lörrach

Germany

In het register ingeschreven onder

RVG 107640

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

Greece: Cetomedica 20 mg/ml Italy: Cetomedica 20 mg/ml Portugal: Cetomedica

Spain: Cetomedica 20 mg/ml The Netherlands: Cetomedica 20 mg/ml

This leaflet was last approved in februari 2012

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

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

Instruction for use – Cytotoxic

Handling of Cetomedica

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

Protection instructions for preparation of Cetomedica Solution for infusion:

1. Protective chamber should be used and protective gloves as well as protective gown should be worn. If there is a no protective chamber available mouth cover and goggles should be used.
2. Opened containers, like injection vials and infusion bottles and used cannulae, syringe, catheters, tubes and residuals of cytostatics should be considered as hazardous waste and undergo disposal according to the 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 as HAZARDOUS WASTE.

In the event of Cetomedica contact with the skin, the areas 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 aria thoroughly with water. If you have any discomfort, contact a doctor. In case of contact of Cetomedica with eyes, wash them thoroughly with plenty of water, contact an ophthalmologist immediately.

Preparation of infusion solution

Cetomedica concentrate for solution for infusion 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 Cetomedica 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 reconstitution the product should be discarded according to the standard procedures for cytotoxic agents.

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

Disposal

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