IRINOTECAN KABI 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Irinotecan Kabi 20 mg/ml Concentrate for Solution for Infusion EFG

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

Contents of the pack

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

1. What is Irinotecan Kabi and what is it 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 therapy based on fluorouracil

2. What you need to know before you use Irinotecan Kabi

Do not use Irinotecan Kabi

• If you have chronic inflammatory intestinal 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 breastfeeding woman (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 (a herbal extract containing Hypericum)
• If you take or have recently taken live attenuated vaccines (vaccines against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, flu) 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:

Consult your doctor, pharmacist, or nurse before starting treatment with irinotecan.

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

If you have Gilbert's syndrome, a hereditary condition that may cause elevated bilirubin levels and jaundice (yellow skin and eyes).

Diarrhea

Irinotecan may cause diarrhea, which in some cases can be severe. This can start a few hours or a few days after infusion. If left untreated, it can lead to dehydration and severe chemical imbalances, which can be fatal. Your doctor will prescribe a medicine to help prevent or control this side effect. Make sure to get the medicine immediately, to have it at home when you need it.

• Take the medicine as prescribed at the first symptom of loose stools or frequent bowel movements.
• Drink plenty of water and (or) salty drinks (sparkling water, soda water, or broth)
• Call your doctor or nurse if you continue to have diarrhea, especially if it lasts more than 24 hours or if you feel weak, dizzy, or faint.

Neutropenia (decrease in some white blood cells)

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

Blood tests

It is likely that your doctor will have your blood tested before and during your treatment, to check if there are any effects of the medicine on your blood counts or on the results of your blood chemistry tests. Based on the test results, you may need medicines to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medicine, or even stop treatment altogether. Keep all your appointments for medical visits and laboratory tests.

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

Nausea and vomiting

You may have nausea and vomiting on the day you receive this medicine or in the first few days after administration. Your doctor may give you medicines before your treatment to help prevent nausea and vomiting. Your doctor may also prescribe anti-nausea medicines that you can take at home. Have these medicines on hand for when you need them. Inform your doctor if you cannot take fluids by mouth 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 notice any of these symptoms, as there are medicines that can help control them.

Pulmonary disorders

Rarely, people being treated with this medicine have serious lung problems. Inform your doctor immediately if you have a new or worsening cough, difficulty breathing, and fever. Your doctor may need to stop treatment to treat this problem.

This medicine may increase the risk of having significant blood clots in the veins of the legs or lungs, which can 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 move your bowels, especially if you also have bloating and loss of appetite.

Radiation therapy

If you have recently received pelvic or abdominal radiation therapy, you may be at higher risk of developing bone marrow suppression. Please talk to your doctor before starting irinotecan.

Kidney function

There have been cases of decreased kidney function.

Cardiac disorders

Inform your doctor if you have or have had heart disease or if you have previously received anticancer medicines. Your doctor will closely monitor you and discuss with you how to reduce risk factors (such as smoking, high blood pressure, and high fat content).

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.

Others

This medicine may cause sores in the mouth or on the lips, often within the first few weeks after starting treatment. This can cause mouth pain, bleeding, or even problems eating. Your doctor or nurse may suggest ways to reduce this, such as changing the way you eat or brush your teeth. If necessary, your doctor may prescribe medicines to help calm the 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 you are using this medicine in combination with other anticancer medicines for your condition, make sure to also read the package leaflets of the other medicines.

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

Using 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 may 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 (a herbal dietary supplement)
• Live attenuated vaccines
• Medicine for the treatment of HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• Medicines used to decrease 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 used during anesthesia and surgery (suxamethonium)
• 5-fluorouracil/folinic acid
• Bevacizumab (a vascular endothelial growth factor inhibitor)
• Cetuximab (an epidermal growth factor receptor inhibitor)

Inform your doctor, pharmacist, or nurse before you are given irinotecan if you are already receiving or have recently received chemotherapy (and radiation therapy).

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

This medicine may cause severe diarrhea. Try to avoid laxatives and stool softeners while taking this medicine.

There may be more medicines that interact with irinotecan. Consult your doctor, pharmacist, or nurse about your other medicines, herbs, and supplements, and whether alcohol may 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 and up to 6 months after finishing treatment.

If you are a man, you must use an effective contraceptive method during and up to 3 months after finishing treatment. It is important to consult with your doctor what types of contraceptives can be used with this medicine.

Pregnancy

This medicine may cause harm to the fetus if used during conception or during pregnancy. Before starting treatment, your doctor will make sure 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 were measured in breast milk. Breastfeeding must be discontinued during the duration of 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 possible risk with this medicine and the options that may preserve your ability to have children.

Driving and using machines

During the first 24 hours after administration of irinotecan, you may feel dizzy or have changes in vision. If these symptoms occur, do not drive or use tools or machines.

Irinotecan Kabi contains sorbitol and sodium

This medicine contains 45 mg of sorbitol in each 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 can cause serious side effects.

You must inform your doctor before receiving this medicine if you (or your child) have HFI or if your child can no longer take sweet foods or drinks because they feel sick, vomit, or have unpleasant effects such as bloating, stomach cramps, or diarrhea.

This medicine contains less than 1 mmol of sodium (23 mg) per dose unit, i.e., it is 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 not sure.

Irinotecan will be administered to you by healthcare professionals.

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

Some people are genetically more prone to having certain side effects with this medicine.

The amount of irinotecan that will be administered to you depends on many factors, including your height and weight, your overall health, and the type of cancer or condition being treated. Your doctor will determine your dose and administration schedule.

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

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

Inform your caregivers if you feel burning, pain, or swelling around the IV needle when you are given irinotecan. If the medicine leaks out of the vein, it can cause damage to the injection site. If you experience pain or notice redness or swelling at the IV site while you are being administered irinotecan, alert your healthcare professional immediately.

There are currently several recommended treatment regimens for irinotecan. It is usually 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, and overall health, your 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. The symptoms of overdose may include some of the serious side effects mentioned in this package leaflet.

If you miss a dose of Irinotecan

Inform your doctor for instructions if you miss a scheduled dose of irinotecan.

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

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them.

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

Get emergency medical help if you have any of these 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 of runny nose, increased salivation, watery eyes, sweating, flushing, abdominal cramps. (this may occur while the medicine is being administered. If so, notify your healthcare professional quickly. Medication can be given to stop and/or reduce this early adverse effect).
• Late diarrhea: occurs more than 24 hours after receiving this medicine. Due to the risk of dehydration and electrolyte imbalance with diarrhea, it is essential to be in contact with healthcare professionals for monitoring and advice on medication and dietary modifications.

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

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

† Frequent: may affect up to 1 in 10 people

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

• Severe, persistent, or bloody diarrhea (which may be associated with stomach pain or fever) caused by bacteria called (Clostridium difficile)
• Blood infection
• Dehydration (due to diarrhea 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 that causes wheezing and difficulty breathing (see section 2)
• Hiccup
• Intestinal obstruction
• Enlarged colon
• Intestinal bleeding
• Inflammation of the large intestine
• Abnormal test results
• Hole in the intestine
• Fatty liver disease
• Skin reactions
• Reactions at the site where the medicine was administered
• Low potassium levels in the blood
• Low salt levels in the blood, especially related to diarrhea and vomiting
• Muscle cramps
• Kidney problems *
• Low blood pressure *
• Fungal infections
• Viral infections

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing 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 expiration date that appears on the packaging and label after CAD. The expiration date is the last day of the month indicated.

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

After dilution:

The chemical and physical stability has been tested for 24 hours if stored below 25 ºC and for 48 hours if stored between 2 ºC and 8 ºC.

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

Do not use this medicine if you observe visible particles in the concentrate or in the infusion solution.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Irinotecan Kabi

The active ingredient 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 injectable preparations, sodium hydroxide, and hydrochloric acid (for pH adjustment).

Appearance of the Product and Package Contents

Irinotecan Kabi 20 mg/ml concentrate for solution for infusion is a slightly yellowish solution without visible particles, packaged in glass vials.

The product is available in single-dose 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 some package 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 medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Date of the Last Revision of this Leaflet:April 2024

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

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This information is intended only for healthcare professionals:

Instructions for Use

Cytotoxic

Handling of irinotecan

Like other antineoplastic agents, irinotecan should be handled with caution. The dilution should be carried out in aseptic conditions by trained personnel and in a designated area. Precautions should be taken to avoid contact with the skin and mucous membranes.

Protection instructions for the preparation of irinotecan solution for infusion.

1. The preparation must be carried out in a protective hood using gloves and protective clothing. If a protective hood is not available, safety glasses and a mask should be used.
2. Open containers, such as vials, infusion bottles, and used cannulas, syringes, catheters, tubes, and cytostatic residues, should be considered as hazardous waste and disposed of according to local regulations for the handling of HAZARDOUS WASTE.
3. In case of spills, follow these instructions:
   • protective clothing should be worn.
   • broken glass should be collected and thrown away in a container for HAZARDOUS WASTE.
   • contaminated surfaces should be washed thoroughly with a large amount of cold water.
   • washed surfaces with water should be completely dried, and the materials used should be eliminated as HAZARDOUS WASTE.

1. In case irinotecan comes into contact with the skin, rinse the affected area with a large amount of running water and then wash with water and soap. In case of contact with the mucous membranes, wash the contact area thoroughly with water. If you feel any discomfort, consult a doctor.
2. In case of irinotecan contact with the eyes, rinse them thoroughly with a large amount of water. Contact an ophthalmologist immediately.

Preparation of the Infusion Solution

Irinotecan concentrate for solution for infusion is developed to be used in intravenous infusions after prior dilution in suitable diluents, either a 0.9% sodium chloride infusion solution or a 5% glucose solution. With a graduated syringe, withdraw from the vial, in an aseptic manner, the necessary amount of irinotecan concentrate for solution and inject it into a 250 ml infusion bag or bottle. The infusion should be mixed carefully by manual rotation.

The final solution is transparent, colorless, or slightly yellowish and without visible particles.

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

Read the leaflet for the validity period of the diluted product.

Irinotecan should notbe administered as an intravenous bolus or as an intravenous infusion with a duration of less than 30 minutes or more than 90 minutes.

Elimination

All materials that have been used for the preparation, administration, or that have come into contact with Irinotecan should be eliminated according to local regulations for the handling of cytotoxic compounds.