Irinotecan Kabi 20 mg/ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Irinotecan Kabi 20 mg/ml concentrate for solution for infusion EFG

irinotecan hydrochloride trihydrate

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Irinotecan Kabi is and what it is used for
2. What you need to know before using Irinotecan Kabi
3. How to use Irinotecan Kabi
4. Possible adverse effects
5. How to store Irinotecan Kabi
6. Contents of the pack and other information

1. What Irinotecan Kabi is and what it is used for

Irinotecan is an anticancer medicine that contains the active substance irinotecan hydrochloride trihydrate.

Irinotecan hydrochloride trihydrate interferes with the growth and spread of cancer cells in the body.

Irinotecan is indicated in combination with other medicines for the treatment of patients with advanced or metastatic cancer of the colon or rectum.

Irinotecan may be used as monotherapy in patients with metastatic cancer of the colon or rectum whose disease has recurred or progressed after initial fluorouracil-based therapy.

2. What you need to know before using Irinotecan Kabi

Do not use Irinotecan Kabi

• If you have chronic inflammatory bowel disease and/or intestinal obstruction
• If you are allergic to irinotecan hydrochloride trihydrate or to any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”)
• If you are a woman who is breastfeeding (see section 2)
• If your bilirubin levels are more than 3 times the upper limit of normal
• If you have severe bone marrow failure
• If your general condition is poor (WHO performance status greater than 2)
• If you are taking or have recently taken St. John’s Wort (an herbal extract containing Hypericum)
• If you are taking or have recently taken live attenuated vaccines (vaccines against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza) and during the 6 months after stopping chemotherapy.

If you receive irinotecan in combination with other medicines, please make sure to also read the package leaflet of the other medicines regarding additional contraindications.

Warnings and precautions:

Talk to your doctor, pharmacist, or nurse before starting to use irinotecan.

Take special care with irinotecan. The use of irinotecan should be restricted to specialized units for administration of cytotoxic chemotherapy and should only be administered under the supervision of a physician experienced in the use of anticancer drugs.

If you have Gilbert’s syndrome, a hereditary condition that may cause elevated bilirubin levels and jaundice (yellowing of the skin and eyes).

Diarrhea

Irinotecan can cause diarrhea, which in some cases may be severe. This may begin within hours or a few days after infusion. If not treated, dehydration and serious electrolyte imbalances may occur, which can be life-threatening. Your doctor will prescribe a medication to help prevent or control this adverse effect. Make sure to obtain the medication immediately so you have it at home when needed.

• Take the medication as prescribed at the first sign of loose stools or frequent bowel movements.
• Drink plenty of water and/or electrolyte-containing fluids (mineral water, soda water, or broth).
• Call your doctor or nurse if diarrhea continues, especially if it lasts more than 24 hours or if you feel weak, dizzy, or faint.

Neutropenia (reduction in certain white blood cells)

This medicine may reduce the number of your white blood cells, mainly in the weeks following treatment. This may increase the risk of infection. Be sure to inform your doctor or nurse immediately if you have signs of infection such as fever (38°C or higher), chills, pain when urinating, new cough, or sputum. Avoid close contact with people who are ill or have an infection. Inform your doctor if you develop symptoms of infection.

Blood tests

Your doctor will likely perform blood tests before and during your treatment to monitor for effects of the medicine on blood counts or blood chemistry results. Based on the test results, you may need medications to help manage side effects. Your doctor may also need to reduce or delay your next dose of this medicine, or even stop treatment completely. Keep all your medical appointments and laboratory test visits.

This medicine may decrease the number of platelets in the weeks following its use, which may increase the risk of bleeding. Talk to your doctor before taking any medication or supplement that may affect your body’s ability to stop bleeding, such as aspirin or products containing aspirin, warfarin, or vitamin E. Inform your doctor immediately if you experience unusual bruising or bleeding such as nosebleeds, bleeding gums when brushing your teeth, or black, tarry stools.

Nausea and vomiting

You may experience nausea and vomiting on the day you receive this medicine or in the first few days after administration. Your doctor may give you medications before treatment to help prevent nausea and vomiting. Your doctor will likely prescribe anti-nausea medications for you to take at home. Keep these medications on hand for when you need them. Inform your doctor if you are unable to take fluids orally due to nausea and vomiting.

Acute cholinergic syndrome

This medicine may affect the part of your nervous system that controls body secretions, leading to what is known as cholinergic syndrome. Symptoms may include runny nose, increased saliva, excessive tearing, sweating, flushing, abdominal cramps, and diarrhea. Inform your doctor or nurse immediately if you experience any of these symptoms, as medications are available to help control them.

Pulmonary disorders

Rarely, people receiving this medicine may develop serious lung problems. Inform your doctor immediately if you develop a new or worsening cough, difficulty breathing, or fever. Your doctor may need to discontinue treatment to manage this condition.

This medicine may increase the risk of developing serious blood clots in the veins of the legs or lungs, which may travel to other parts of the body such as the lungs or brain. Inform your doctor immediately if you notice chest pain, difficulty breathing, or swelling, pain, redness, or warmth in an arm or leg.

Chronic intestinal inflammation and/or intestinal obstruction

Inform your doctor if you have abdominal pain and cannot pass stools, especially if you also have bloating and loss of appetite.

Radiation therapy

If you recently received pelvic or abdominal radiation therapy, you may be at increased risk of developing bone marrow suppression. Please speak with your doctor before starting irinotecan.

Renal function

Cases of impaired renal function have been reported.

Cardiac disorders

Inform your doctor if you have or have had heart disease or if you have previously received anticancer medicines. Your doctor will monitor you closely and discuss with you how risk factors (e.g., smoking, high blood pressure, high fat levels) can be reduced.

Vascular disorders

Irinotecan is rarely associated with blood flow disorders (blood clots in the veins of the legs and lungs) and may rarely occur in patients with multiple risk factors.

Other

This medicine may cause mouth or lip sores, often within the first few weeks after starting treatment. This may cause mouth pain, bleeding, or difficulty eating. Your doctor or nurse may suggest ways to reduce this, such as changing how you eat or brush your teeth. If needed, your doctor may prescribe medications to help relieve pain.

For information on contraception and breastfeeding, see the information provided later in the section Contraception, pregnancy, breastfeeding, and fertility.

Inform your doctor or dentist that you are being treated with this medicine if you are planning to undergo surgery or any other procedure.

If used in combination with other anticancer medicines for your condition, ensure you also read the package leaflets of the other medicines.

If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.

Use of Irinotecan with other medicines

Irinotecan may interact with other medicines and supplements, which may increase or decrease the level of this medicine in the blood. Inform your doctor or pharmacist if you are using, have recently used, or might need to use any of the following medicines:

• Medicines used to treat epilepsy (carbamazepine, phenobarbital, phenytoin, or fosphenytoin)
• Medicines used to treat fungal infections (ketoconazole, itraconazole, voriconazole, and posaconazole)
• Medicines used to treat bacterial infections (clarithromycin, erythromycin, and telithromycin)
• Medicine used to treat tuberculosis (rifampicin and rifabutin)
• St. John’s Wort or hypericum (an herbal dietary supplement)
• Live attenuated vaccines
• Medicine used to treat HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• Medicines used to suppress the immune system to prevent transplant rejection (cyclosporine and tacrolimus)
• Medicines used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamide)
• Vitamin K antagonists (anticoagulants used to thin the blood such as warfarin)
• Medicines used to relax muscles during anesthesia and surgery (suxamethonium)
• 5-fluorouracil/folinic acid
• Bevacizumab (an inhibitor of blood vessel growth)
• Cetuximab (an EGFR inhibitor)

Inform your doctor, pharmacist, or nurse before receiving irinotecan if you are currently receiving or have recently received chemotherapy (and radiotherapy).

Do not start or stop taking any medicines while being treated with irinotecan without first talking to your doctor.

This medicine can cause severe diarrhea. Avoid using laxatives and stool softeners while taking this medicine.

There may be other medicines that interact with irinotecan. Consult your doctor, pharmacist, or nurse about your other medicines, herbs, and supplements, and whether alcohol could cause problems with this medicine.

Contraception, pregnancy, breastfeeding, and fertility

Contraception

If you are a woman of childbearing age, you must use effective contraceptive methods during treatment and for at least 6 months after treatment ends.

If you are a man, you must use an effective contraceptive method during treatment and for at least 3 months after treatment ends. It is important to consult your doctor about which types of contraceptives can be used with this medicine.

Pregnancy

This medicine may harm the fetus if used during conception or pregnancy. Before starting treatment, your doctor will ensure you are not pregnant.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Breastfeeding

Irinotecan and its metabolite have been detected in breast milk. Breastfeeding must be discontinued during treatment with this medicine.

If you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

Fertility

No studies have been conducted; however, this medicine may affect fertility. Before using this medicine, talk to your doctor about the potential risk with this medicine and options that may preserve your ability to have children.

Driving and using machines

During the first 24 hours after receiving irinotecan, you may experience dizziness or visual disturbances. If these symptoms occur, do not drive or operate tools or machinery.

Irinotecan Kabi contains sorbitol and sodium

This medicine contains 45 mg of sorbitol per ml of concentrate. Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not receive this medicine. Patients with HFI cannot break down fructose, which may cause serious side effects.

You must inform your doctor before receiving this medicine if you (or your child) have HFI or if your child becomes ill, vomits, or experiences unpleasant effects such as bloating, stomach cramps, or diarrhea after consuming sweet foods or drinks.

This medicine contains less than 1 mmol of sodium (23 mg) per dose unit, i.e., essentially “sodium-free”.

3. How to use Irinotecan Kabi

Always use this medicine exactly as your doctor has told you. Consult your doctor if you are unsure.

Irinotecan will be administered to you by healthcare professionals.

Your doctor may recommend a DNA test before your first dose of irinotecan.

Some people are genetically more likely to experience certain side effects with this medicine.

The amount of irinotecan you will be given depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated. Your doctor will determine your dose and dosing schedule.

Irinotecan is injected into a vein through an intravenous (IV) line. You will receive this injection at a clinic or hospital. Irinotecan must be administered slowly, and the intravenous infusion may take up to 90 minutes to complete.

You may be given other medications to prevent nausea, vomiting, diarrhea, and other side effects while you are receiving irinotecan. You may need to continue taking these medications for at least one day after the irinotecan infusion.

Inform your caregivers if you feel burning, pain, or swelling around the intravenous needle when irinotecan is being injected. If the medication leaks out of the vein, it may cause damage at the injection site. If you experience pain or notice redness or swelling at the IV injection site while irinotecan is being administered, alert your healthcare professional immediately.

There are currently several recommended treatment regimens for irinotecan. It is generally administered once every 3 weeks (irinotecan alone) or once every 2 weeks (irinotecan administered in combination with 5-Fluorouracil/folinic acid (5FU/FA)). The dose will depend on a number of factors, including the treatment regimen, your body size, age, general health status, blood counts, how well your liver is functioning, whether you have received radiation to the abdomen/pelvis, and whether you have any side effects such as diarrhea.

Only your doctor can assess the duration of treatment.

If you use more Irinotecan than you should

Seek emergency medical attention. Symptoms of overdose may include some of the serious adverse effects mentioned in this leaflet.

If you forget to use Irinotecan

Inform your doctor so they can provide instructions if you miss a scheduled dose of irinotecan.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Some adverse effects could be serious. You must contact your doctor immediately if you experience any of the following serious adverse effects (see section 2).

Seek emergency medical help if you have any symptoms of an allergic reaction: hives; difficulty breathing; swelling of the face, lips, tongue, or throat.

• Diarrhea (see section 2).
• Early diarrhea: occurs within the first 24 hours after receiving this medicine, accompanied by symptoms such as runny nose, increased salivation, watery eyes, sweating, flushing, abdominal cramps. (This may occur while the medicine is being administered. If so, inform your healthcare professional immediately. Medication may be given to stop and/or reduce this early adverse effect.)
• Late diarrhea: occurs more than 24 hours after receiving this medicine. Because of the risk of dehydration and electrolyte imbalances with diarrhea, it is important to contact healthcare professionals for monitoring, and for advice on medication and dietary modifications.

Tell your doctor or nurse if you experience any of the following symptoms:

Symptoms	Frequency *in monotherapy	Frequency † in combination therapy
Abnormally low number of white blood cells which could increase the risk of infection	Very common	Very common
Low number of red blood cells causing fatigue and shortness of breath	Very common	Very common
Decreased appetite	Very common	Very common
Cholinergic syndrome (see Special precautions with irinotecan)	Very common	Very common
Vomiting	Very common	Very common
Nausea	Very common	Very common
Abdominal pain	Very common	Common
Reversible hair loss	Very common	Very common
Inflammation of mucous membranes	Very common	Very common
Fever	Very common	Common
Feeling weak or lacking energy	Very common	Very common
Low platelet count (blood cells that help with clotting) which may cause bruising or bleeding	Common	Very common
Abnormal blood test results for liver function	Common	Very common
Infection	Common	Common
Low white blood cell count with fever	Common	Common
Difficulty passing stools	Common	Common
Abnormal blood test results for kidney function	Common	Frequency not known

• Very common: may affect more than 1 in 10 people

† Common: may affect up to 1 in 10 people

Frequency not known: cannot be estimated from the available data.

• Severe, persistent or bloody diarrhoea (which may be associated with stomach pain or fever) caused by bacteria called (Clostridium difficile)

• Blood infection

• Dehydration (due to diarrhoea and vomiting)

• Dizziness, rapid heartbeat and pale skin (a condition called hypovolemia)

• Allergic reaction

• Temporary speech disorders during or shortly after treatment

• Numbness and tingling

• High blood pressure (during or after infusion)

• Heart problems *

• Lung disease causing wheezing and difficulty breathing (see section 2)

• Hiccups

• Bowel obstruction

• Enlarged colon

• Bleeding from the intestines

• Inflammation of the large intestine

• Abnormal blood test results

• Hole in the intestine

• Fatty liver disease

• Skin reactions

• Reactions at the site where the medicine was administered

• Low blood potassium levels

• Low blood sodium levels, mainly related to diarrhoea and vomiting

• Muscle cramps

• Kidney problems *

• Low blood pressure *

• Fungal infections

• Viral infections

• Uncommon cases of these events have been observed in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or blood infections.

Reporting of adverse reactions

If you experience any type of adverse reaction, talk to your doctor, pharmacist or nurse, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Irinotecan Kabi

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

Do not use this medicine after the expiry date stated on the container and label after EXP. The expiry date refers to the last day of the month indicated.

Store below 25 °C. Keep the vial in the outer packaging to protect it from light. Do not freeze.

After dilution:

Chemical and physical in-use stability has been demonstrated for 24 hours when stored below 25 °C and for 48 hours when stored between 2 °C and 8 °C.

From a microbiological standpoint, the product should be used immediately after first opening. If not, the time and conditions of storage of the product in use before administration shall be the responsibility of the user and normally should not exceed 24 hours between 2 °C and 8 °C, unless the dilution has been carried out under controlled and validated aseptic conditions.

Do not use this medicine if visible particles are observed in the concentrate or in the infusion solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Irinotecan Kabi

The active substance is irinotecan hydrochloride trihydrate. Each ml contains 20 mg of irinotecan hydrochloride trihydrate, equivalent to 17.33 mg of irinotecan.

Each 2 ml vial contains 40 mg of irinotecan hydrochloride as trihydrate.

Each 5 ml vial contains 100 mg of irinotecan hydrochloride as trihydrate.

Each 15 ml vial contains 300 mg of irinotecan hydrochloride as trihydrate.

Each 25 ml vial contains 500 mg of irinotecan hydrochloride as trihydrate.

The other components are sorbitol (E420), lactic acid, water for injections, sodium hydroxide and hydrochloric acid (to adjust pH).

Appearance of the product and contents of the container

Irinotecan Kabi 20 mg/ml concentrate for solution for infusion is a slightly yellowish solution free from visible particles, supplied in glass vials.

The product is available in single-use vials containing 40 mg/2 ml, 100 mg/5 ml, 300 mg/15 ml or 500 mg/25 ml. These vials are for single use only.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Fresenius Kabi España SAU

Marina 16

08005 Barcelona

Spain

Manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Czech Republic	Irinotecan Kabi
Denmark	Irinotecan Fresenius Kabi
Estonia	Irinotecan Kabi 20 mg/ml
Finland	Irinotecan Fresenius Kabi 20 mg/ml concentrate for infusion solution
Hungary	Irinotecan Kabi 20 mg/ml concentrate for infusion solution
Ireland	Irinotecan 20 mg/ml concentrate for solution for infusion
Italy	Irinotecan Kabi infusion
Latvia	Irinotecan Kabi 20 mg/ml concentrate for infusion solution
Lithuania	Irinotecan Kabi 20 mg/ml concentrate for infusion solution
Poland	Irinotecan Kabi
Slovak Republic	Irinotecan Kabi 20 mg/ml infusion concentrate
Spain	Irinotecan Kabi 20 mg/ml concentrate for solution for infusion EFG
United Kingdom (Northern Ireland)	Irinotecan 20 mg/ml concentrate for solution for infusion

Date of the most recent review of this leaflet: April 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended for healthcare professionals only:

Instructions for use

Cytotoxic

Handling of irinotecan

Like other antineoplastic agents, irinotecan must be handled with caution. Dilution must be performed under aseptic conditions by trained personnel in a designated area. Precautions should be taken to avoid contact with skin and mucous membranes.

Protective instructions for the preparation of irinotecan solution for infusion.

1. Preparation must be carried out in a safety cabinet using gloves and protective clothing. If a safety cabinet is not available, safety goggles and a mask must be used.

2. Opened containers, such as vials, infusion bottles and used cannulas, syringes, catheters, tubes, and cytostatic waste, must be considered hazardous waste and must be disposed of in accordance with local regulations for handling HAZARDOUS WASTE.

3. In case of spills, follow these instructions:

   • protective clothing must be worn.
   • broken glass must be collected and discarded into a container for HAZARDOUS WASTE.
   • contaminated surfaces must be thoroughly washed with a large amount of cold water.
   • surfaces washed with water must be completely dried and the materials used must be disposed of as HAZARDOUS WASTE.

4. If irinotecan comes into contact with the skin, rinse the affected area thoroughly with copious amounts of running water and then wash with water and soap. In case of contact with mucous membranes, thoroughly wash the exposed area with water. If any discomfort is experienced, consult a physician.

5. In case of irinotecan contact with the eyes, rinse thoroughly with copious amounts of water. Contact an ophthalmologist immediately.

Preparation of the infusion solution

Irinotecan concentrate for solution for infusion is intended for intravenous infusion after dilution in appropriate diluents, either a 0.9% sodium chloride or 5% glucose infusion solution. Using a graduated syringe, aseptically withdraw the required amount of irinotecan concentrate for solution and inject it into a 250 ml infusion bag or bottle. The infusion solution should be mixed carefully by manual rotation.

The final solution is transparent, colourless or slightly yellowish, and free from visible particles.

If any precipitate is observed either in the vial or after dilution, the product must be discarded according to standard procedures for disposal of cytotoxic agents.

Refer to the package leaflet for the shelf life of the diluted product.

Irinotecan must not be administered as an intravenous bolus or as an intravenous infusion with a duration of less than 30 minutes or more than 90 minutes.

Disposal

All materials used in the preparation, administration, or that have otherwise come into contact with irinotecan must be disposed of in accordance with local regulations for handling cytotoxic compounds.