Irinotecan Hydrochloride 20 Mg/Ml Concentrate For Solution For Infusion
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Irinotecan Hydrochloride 20mg/ml Concentrate for Solution for Infusion
Irinotecan hydrochloride trihydrate A SANDOZ
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 or pharmacist. This includes any possible side effects not listed in this leaflet.
In this leaflet:
1. What Irinotecan Hydrochloride is and what it is used for
2. What you need to know before you use Irinote can Hydrochloride
3. How to use Irinotecan Hydrochloride
4. Possible side effects
5. How to store Irinotecan Hydrochloride
6. Contents of the pack and other information
IWhat Irinotecan Hydrochloride is ■ and what it is used for
Irinotecan Hydrochloride belongs to a group of medicines called cytostatics (anti-cancer medicines). Irinotecan Hydrochloride is used for the treatment of advanced cancer of the colon and rectum in adults, either in a combination with other medicines (i.e. 5-fluorouracil/folinic acid, bevacizumab, cetuximab, capecitabine) or alone.
Do not use Irinotecan Hydrochloride:
• if you are allergic (hypersensitive) to irinotecan hydrochloride trihydrate or any of the other ingredients of Irinotecan Hydrochloride
• if you have any other bowel disease or a history of bowel obstruction
• if you are pregnant or breast-feeding
• if you have increased levels of bilirubin in the blood (more than 3 times the upper limit of normal)
• if you have 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
About additional contraindications of cetuximab, bevacizumab or capecitabine please read the product information of these medicines.
Warnings and precautions
Take special care with Irinotecan Hydrochloride: This medicine is intended for adults only. Check with your doctor if this medicine has been prescribed for use in a child.
Special care is also needed in elderly patients.
As Irinotecan Hydrochloride 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 Hydrochloride
During administration of Irinotecan Hydrochloride (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.
fluids described above. Follow the doctor’s instructions. The anti-diarrhoeal treatment should not be used to prevent a further episode of diarrhoea, even though 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 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 unit immediately.
- Neutropenia
Irinotecan Hydrochloride 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 Hydrochloride 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 Hydrochloride is started and before every following treatment cycle the liver function should be monitored (by blood tests).
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 unit supervising the Irinotecan Hydrochloride treatment.
- 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
Heart attacks have been observed following treatment with Irinotecan Hydrochloride. If you have any heart disease, known risk factors for heart disease, or previous cytotoxic chemotherapywill monitor you closely. Action should be taken to try to minimize all modifiable risk factors for heart problems (e.g. smoking, high blood pressure,fat).
- Infections
You might get serious infections or face reduced response to vaccinations during therapy with Irinotecan Hydrochloride. Your doctor will try to avoid vaccinations during therapy with Irinotecan Hydrochloride.
Other medicines and Irinotecan Hydrochloride
Please tell your doctor 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.
Some medicines may alter the effects of Irinotecan Hydrochloride e.g. ketoconazole (for the treatment of fungal infections), rifampicin (for the treatment of tuberculosis), atazanavir sulphate (for the treatment of HIV-1) and some medicines for the treatment of epilepsy (carbamazepine, phenobarbital and phenytoin).
The herbal medicine St John’s Wort (Hypericum perforatum) may not be used concurrent with Irinotecan Hydrochloride 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 affect of some medicines used during surgery.
You should not get yellow fever vaccine during during therapy with Irinotecan Hydrochloride. Tell your doctor that you are using this medicine if you require any other vaccine, as this might result in side effects.
2) From the day after treatment with Irinotecan Hydrochloride 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 Irinotecan Hydrochloride (“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 (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 unit at the hospital supervising the Irinotecan Hydrochloride 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 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
Note! Do not take any treatment for diarrhoea other than that given to you by your doctor and the
If you receive Irinotecan Hydrochloride in combination with a medicinal product containing cetuximab, bevacizumab, cyclosporine, tacrolimus or capecitabine, please make sure that you also read the package inserts for those products.
Pregnancy:
You must not receive Irinotecan Hydrochloride during pregnancy, especially during the first trimester, unless clearly necessaryif you are pregnant. 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. Still, if you become pregnant, think you could be pregnant, or could become pregnant during this period you must immediately inform your doctor.
Breast-feeding:
It is not known whether Irinotecan Hydrochloride is excreted in human milk. Consequently, you must not breast-feed while you are treated with Irinotecan Hydrochloride.
Driving and using machines
In some cases Irinotecan Hydrochloride 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 Hydrochloride you may feel dizzy or have visual disturbances. If this happens to you do not drive or use any tools or machines.
Important information about some of the ingredients of Irinotecan Hydrochloride
Irinotecan Hydrochloride contains sorbitol. If you suffer from intolerance to some sugars, tell your doctor before you are given this medicinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium- free”.
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THE FOLLOWING INFORMATION IS INTENDED FOR MEDICAL OR HEALTHCARE PROFESSIONALS ONLY
Instruction for use
Cytotoxic
Handling of Irinotecan Hydrochloride As with all antineoplastic agents, caution should be exercised when handling Irinotecan Hydrochloride. 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 Hydrochloride solution 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 as HAZARDOUS
waste
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3 How to use Irinotecan ■ Hydrochloride
Irinotecan Hydrochloride will be given as an infusion into your veins over a period of 30-90 minutes. Theamount of infusion 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. Your doctor will calculate your body surface area in square meters (m2).
• If you have previously been treated with 5-fluorouracil you will normally be treated with Irinotecan Hydrochloride alone starting with a dose of 350 mg/m2 every 3 weeks.
• If you have not had previous chemotherapy you will normally receive 180 mg/m2 Irinotecan Hydrochloride every two weeks. This will be followed by folinic acid and 5-fluorouracil.
• If you are treated with Irinotecan Hydrochloride in combination with cetuximab you will normally receive the same dose of irinotecan as administered in the last cycles of the prior irinotecan containing regimen.
Irinotecan Hydrochloride must not be administered earlier than 1 hour after the end of the cetuximab infusion.
If you receive Irinotecan Hydrochloride in combination with cetuximab, please consult the cetuximab leaflet.
If you receive Irinotecan Hydrochloride in combination with bevacizumab, please consult the bevacizumab leaflet.
If you receive Irinotecan Hydrochloride 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.
Like all medicines, Irinotecan Hydrochloride 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 Irinotecan Hydrochloride”.
Very common side effects (affects more than 1 user in 10):
• Neutropenia (decreased number of some white blood cells), which increases the risk of infections.
• Anaemia (decreased number of red blood cells), which can make the skin pale and cause weakness and breathlessness.
• In combination therapy, thrombocytopenia (decreased number of blood platelets) causing bruises, tendency to bleed and abnormal bleeding.
• In monotherapy, fever and infection.
• Delayed severe diarrhoea.
• In monotherapy, severe nausea, and vomiting.
• In monotherapy, fever in the absence of infection and without concomitant severe decrease in the number of some white blood cells (neutropenia).
• Hair loss (the hair grows again after end of treatment).
• In combination therapy, transient and mild to moderate increase in serum levels of some enzymes (SGPT, SGOT, alkaline phosphatase) or bilirubin.
• In combination therapy with capecitabine all grade adverse drug reactions: thrombosis/embolism.
Common side effects (affects 1 to 10 users in 100):
• 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; 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 Hydrochloride.
• In monotherapy, thrombocytopenia (decreased number of blood platelets) causing bruises, tendency to bleed and abnormal bleeding.
• In combination therapy, fever and infections.
• In combination therapy, fever in the absence of infection and without concomitant severe decrease in the number of some white blood cells (neutropenia).
• Infections associated with a severe decrease in the number of some white blood cells (neutropenia) resulting in death in 3 cases. Infections associated with a severe decrease in the number of some 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 and vomiting.
• Feeling weak (asthenia).
• In monotherapy, transient and mild to moderate increase in serum levels of liver enzymes (transaminases, alkaline phosphatase) and bilirubin.
• In combination therapy, transient severe increase in serum levels of bilirubin.
• Transient and mild to moderate increase in levels of creatinine in the blood.
• In combination therapy with capecitabine all grade adverse drug reactions: hypersensitivity reaction, cardiac ischemia/infarction and grade 3 and grade 4 adverse drug reactions: febrile neutropenia, thrombosis/embolism, hypertension, and cardiac ischemia/infarction.
• In combination with capecitabine and bevacizumab: grade 3 and grade 4 adverse drug reactions: neutropenia, thrombosis/embolism, hypertension, and cardiac ischemia/infarction.
Uncommon side effects (affects 1 to 10 users in 1,000):
• Mild allergic reactions including red itchy skin, urticaria, conjunctivitis, rhinitis.
• Mild skin reactions; mild reactions at the infusion site.
• Early effects such as breathing difficulties (dyspnoea).
• Lung disease presenting as shortness of breath, dry cough and inspiratory crackles (interstitial pulmonary disease).
• Partial or complete blockage of the bowel
2x----------------------------------------------
(intestinal obstruction, ileus).
• Gastrointestinal bleeding.
• Bowel inflammation, causing abdominal pain and/or diarrhoea (a condition known as pseudomembraneous 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 (affects 1 to 10 users in 10,000):
• Severe allergic reactions including swelling of the of the hands, feet, ankles, face, lips, mouth or throat which may cause difficulty in swallowing or extreme difficulty breathing (anaphylactic/anaphylactoid reactions). If this happens you should tell your doctor immediately.
• Early effects such as muscular contraction or cramps and numbness (paraesthesia).
• Inflammation of the large bowel causing abdominal pain (colitis including the appendix, ischemic and ulcerative colitis).
• Intestinal perforation; loss of appetite (anorexia); abdominal pain; inflammation of the mucous membranes.
• Symptomatic or asymptomatic inflammation of the pancreas.
• 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 (affects less than 1 user in 10,000):
• Transient speech disorders.
• Increase in levels of some digestive enzymes which break down sugars and fats.
• One case of peripheral thrombocytopenia with antiplatelet antibodies was reported.
If you receive Irinotecan Hydrochloride in combination with a medicine containing cetuximab, bevacizumab or capecitabine, some of the side effects you may experience can also be related to these combination. Such side effects may include an acne-like rash. Therefore, please make sure that you also read the package leaflet for cetuximab, bevacizumab or capecitabine.
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.
5 How to store Irinotecan . Hydrochloride
Keep out of the sight and reach of children.
For single use only.
Before opening
Keep the vial in the outer carton in order to protect from light.
Do not use this medicinal product after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
After opening
The product should be diluted and used immediately after opening.
After dilution
From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally be not longer than 24 hours at 2-80C, unless dilution has taken place in controlled and validated aseptic conditions. Chemical and physical in-use stability have been demonstrated for 28 days at 2-80C as well as at room temperature (20-25°C) with light protection and for 48 hours without light protection. Do not use Irinotecan Hydrochloride if you notice particles in the solution.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.
What Irinotecan Hydrochloride contains
• The active substance is irinotecan hydrochloride trihydrate.
• One ml of concentrate contains 20 mg irinotecan hydrochloride trihydrate equivalent to 17.33 mg of irinotecan.
• One 2 ml vial contains 40 mg irinotecan hydrochloride trihydrate.
• One 5 ml vial contains 100 mg irinotecan hydrochloride trihydrate.
• One 7.5 ml vial contains 150 mg irinotecan hydrochloride trihydrate.
• One 15 ml vial contains 300 mg irinotecan hydrochloride trihydrate.
• One 25 ml vial contains 500 mg irinotecan hydrochloride trihydrate.
• The other ingredients are sorbitol E420, lactic acid, sodium hydroxide and water for injections
What Irinotecan Hydrochloride looks like and contents of the pack
Amber class I glass vial with rubber stopper (fluoropolymer coated bromobutyl rubber stopper), with or without a protective plastic overwrap (Onco-Safe). “Onco-Safe” does not come into contact with the medicinal product and provides additional transport protection, which increases the safety for the medical and pharmaceutical personnel. The vials are sealed with aluminium crimp caps.
Clear, colourless to slightly yellow solution.
Pack sizes:
40 mg/2 ml: 1 vial, 5 vials, 10 vials
100 mg/5 ml: 1 vial, 5 vials, 10 vials
150 mg/7.5 ml: 1 vial, 5 vials, 10 vials
300 mg/15 ml: 1 vial
500 mg/25 ml: 1 vial
Not all pack sizes may be marketed.
Marketing authorisation holder and manufacturer
Sandoz Ltd, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR.
Manufacturer
Lek Pharmaceuticals d.d., Verovska 57, S11526 Ljubljana, Slovenia or
Salutas Pharma GmbH, Otto-von-Guericke-Allee 1, 39179 Barleben, Germany or EBEWE Pharma Ges.m.b.H., Nfg. KG MondseestraGe 11, A-4866 Unterach, Austria.
This leaflet was last revised in 05/2013.
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4. In the event of Irinotecan Hydrochloride 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 Hydrochloride with eyes, wash them thoroughly with plenty of water. Contact an ophthalmologist immediately.
Preparation of infusion solution Irinotecan Hydrochloride 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 o solution for infusion. Aseptically withdraw the required amount of Irinotecan Hydrochloride 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 standard procedures for cytotoxic agents.
Read the package leaflet for the shelf life of the diluted product.
Irinotecan Hydrochloride 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 irinotecan should undergo disposal according to local guidelines for the handling of cytotoxic compounds.
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