Leaflet: information for the user

Irinotecan Kabi 20 mg/ml concentrate for infusion solution EFG

irinotecan hydrochloride trihydrate

Read this 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, consult your doctor, pharmacist or nurse.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1. What isIrinotecan Kabiand what it is used for

2. What you need to know before starting to useIrinotecan Kabi

3. How to useIrinotecan Kabi

4. Possible side effects

5. Storage ofIrinotecan Kabi

6. Contents of the pack and additional information

Irinotecánis an anticancer medication that contains the active substance irinotecan trihydrate hydrochloride.

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

Irinotecan is indicated in combination with other medications for the treatment of patients with advanced or metastatic colorectal cancer.

Irinotecan may be used as monotherapy in patients with metastatic colorectal cancer whose disease has recurred or progressed after initial therapy based on fluorouracil

Do not use Irinotecán 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 components of this medicine (listed in section 6 “Contents of the pack and other information”)
• If you are a woman in lactation (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 taken recently live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, flu) and during the 6 months after stopping chemotherapy

If you receive irinotecan in combination with other medicines, please also read the prospectus of the other medicines with regard to additional contraindications.

Warnings and precautions:

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

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

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

Diarrea

Irinotecan may cause diarrhea, which in some cases can be severe. This may start a few hours or a few days after infusion. If not treated, 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, so you 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 a lot of water and (or) salty drinks (water with gas, soda water or soup)
• 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 about to 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 may increase the risk of 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 getting close to people who are sick or have an infection. Inform your doctor if you develop symptoms of an infection.

Blood tests

Your doctor may analyze your blood before and during treatment to check if there are any effects of the medicine on blood counts or blood chemistry results. Based on the test results, your doctor may need to prescribe 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 medical appointments and laboratory tests.

This medicine may decrease the number of platelets in the weeks following use, which may 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 containing aspirin, warfarin or vitamin E. Inform your doctor immediately if you have unusual bruises or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black and tar-like 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 prescribe anti-nausea medicines that you can take at home. Make sure to have these medicines on hand when you need them. Inform your doctor if you cannot take liquids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

This medicine may affect the part of your nervous system that controls bodily secretions, leading to what is known as acute cholinergic syndrome. Symptoms may include nasal secretion, increased saliva, excessive tears in the eyes, 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 taking this medicine have serious lung problems. Inform your doctor immediately if you have a new cough or worsening cough, difficulty breathing, and fever. Your doctor may need to suspend treatment to treat this problem.

This medicine may increase the risk of 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 heat in an arm or leg.

Chronic inflammatory bowel disease and/or intestinal obstruction

Inform your doctor if you have abdominal pain and cannot move your intestines, especially if you also have swelling and loss of appetite.

Radiation therapy

If you 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.

Renal function

Cases of renal function deterioration have been reported.

Cardiac disorders

Inform your doctor if you have/have had heart disease or if you have received cancer medicines previously. 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 disorders of blood flow (blood clots in the veins of the legs and lungs) and may occur rarely in patients with multiple risk factors.

Other

This medicine may cause mouth sores or lip sores, often within the first few weeks after starting treatment. This may cause mouth pain, bleeding, or even eating problems. 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 lactation, see the information provided later in the section Contraception, pregnancy, lactation and fertility.

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

If you use it in combination with other cancer medicines for your condition, make sure to also read the prospectuses of the other medicines.

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

Use of Irinotecán 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 used recentlyor may need to use any of the followingmedicines:

• 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 dietary herbal supplement)
• Live attenuated vaccines
• Medicine used to treat HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• Medicines used to reduce the immune system to prevent rejection of a transplant (ciclosporin and tacrolimus)
• Medicines used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamida)
• Anticoagulants used to thin the blood, such as warfarin
• Medicines used to relax muscles used during anesthesia and surgery (suxamethonium)
• 5-fluorouracil/acid folinic
• Bevacizumab (an inhibitor of blood vessel growth)
• Cetuximab (an inhibitor of the EGF receptor)

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

Do not start or stop taking medicines while you are taking irinotecan without talking to your doctor first.

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

You may have other medicines that interact with irinotecan. Consult your doctor, pharmacist, or nurse about your other medicines, herbs, and supplements, and if alcohol can cause problems with this medicine.

Contraception, pregnancy, lactation, and fertility

Contraception

If you are a woman of childbearing age, you should use effective contraceptive methods during and for 6 months after completing treatment.

If you are a man, you should use an effective contraceptive method during and for 3 months after completing treatment. It is essential to consult your doctor about the types of contraceptives that can be used with this medicine.

Pregnancy

This medicine may cause problems for the fetus if used during conception or during pregnancy. Before starting treatment, your doctor will ensure that 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.

Lactation

Irinotecan and its metabolite were measured in breast milk.Breastfeeding should be suspended during the duration of your treatment with this medicine.

If you are breastfeeding, please 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 options to preserve your ability to have children.

Driving and operating machines

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

Irinotecán 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) should not receive this medicine. Patients with HFI cannot break down fructose, which can cause severe side effects.

Please 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, which is essentially "sodium-free".

Use this medication exactly as your doctor has told you. Consult your doctor if you are unsure.

Irinotecan will be administered by healthcare professionals.

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

Some people are genetically more prone to certain side effects of this medication.

The amount of irinotecan you receive will depend on many factors, including your height and weight, your overall health, other health problems, 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 should be administered slowly, and the IV 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 receiving irinotecan. You may need to continue using these medications 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 receive irinotecan. If the medication leaks from the vein, it may cause damage to the injection site. If you experience pain or notice redness or swelling at the IV injection site while receiving irinotecan, alert your healthcare professional immediately.

There are currently several recommended treatment programs 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 series of factors, including the treatment schedule, your body size, age, overall health, blood counts, liver function, whether you have received radiation in the abdomen/pelvis, and if you have any side effects such as diarrhea.

Only your doctor can determine the duration of treatment.

If you use more Irinotecan than you should

Seek emergency medical attention. Symptoms of overdose may include some of the severe side effects mentioned in this prospectus.

If you forget to use Irinotecan

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

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

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

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

Get emergency medical help if you have any of the following 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 nasal discharge, increased salivation, watery eyes, sweating, redness, abdominal cramps. (This may occur while the medicine is being administered. If so, inform your healthcare professional quickly. The medication may be given to stop and/or reduce this early side effect).
• Late diarrhea: occurs more than 24 hours after receiving this medicine. Due to the risk of dehydration and electrolyte imbalances with diarrhea, it is essential to be in contact with healthcare professionals for monitoring, and for medication and dietary modification advice.

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

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

† Common: may affect up to 1 in 10 people

Unknown frequency: cannot be estimated from 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 heartbeats, 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)
• Cardiac problems *
• Lung disease that causes wheezing and difficulty breathing (see Section 2)
• Hypophagia
• Intestinal obstruction
• Enlarged colon
• Bleeding from the intestines
• Inflammation of the large intestine
• Abnormal test results
• Intestinal perforation
• Fatty liver disease
• Skin reactions
• Reactions at the site where the medicine was administered
• Low potassium levels in the blood
• Low sodium levels in the blood, especially related to diarrhea and vomiting
• Muscle cramps
• Renal problems *
• Low blood pressure *
• Fungal infections
• Viral infections

* The 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 side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the label after CAD.The expiration date is the last day of the month indicated.

Store below25 °C. Store the vial in the outer packaging to protect it from light.Do not freeze.

After dilution:

Chemical and physical stability has been proven in use for 24 hours if stored below25 °Cand for 48 hours if stored between2 °Cand8 °C.

From a microbiological standpoint, the product must be used immediately after the first opening. If not, the time and storage conditions of the product in use before administration will be the responsibility of the user and should normally not exceed 24 hours between2 °Cand8 °C,unless the dilution was performed in controlled and validated aseptic conditions.

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacisthow to dispose ofthe packaging and themedicines that you no longerneed.By doing so, you will help protect the environment

Composition of Irinotecan Kabi

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

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

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

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

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

The other components are sorbitol (E420), lactic acid, water for injectable preparations, and sodium hydroxide (for pH adjustment).

Appearance of the product and contents of the package

Irinotecan Kabi 20 mg/ml concentrate for solution for infusion is a slightly yellowish and particle-free solution, packaged 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 some package sizes may be commercially available.

Marketing Authorization Holder

Fresenius Kabi España SAU

Marina 16

08005 Barcelona

Spain

Responsible for manufacturing

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:

Last review date of this leaflet:April 2024

For detailed and updated information on this medicinal product, please consult the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Instructions for use

Cytotoxic

Handling of irinotecan

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

Instructions for protection for the preparation of irinotecan solution for infusion.

1.The preparation should be performed 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 bags, and cannulas used, syringes, catheters, tubes, and cytostatic waste, should be considered hazardous waste and disposed of in accordance with local regulations for the handling of HAZARDOUS WASTE.

3.In the event of spills, follow these instructions:

• Wear protective clothing.
• Broken glass should be collected and disposed of in a HAZARDOUS WASTE container.
• Contaminated surfaces should be thoroughly washed with plenty of cold water.
• Washed surfaces with water should be completely dried and materials used should be disposed of as HAZARDOUS WASTE

4.In the event of irinotecan coming into contact with the skin, wash the affected area with plenty of running water and then wash with soap and water. In the event of contact with mucous membranes, wash the affected area thoroughly with water. If you experience any discomfort, consult a doctor.

5.In the event of irinotecan coming into contact with the eyes, wash them thoroughly with plenty of water. Immediately contact an ophthalmologist.

Preparation of the infusion solution

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

The final solution is transparent, colorless, or slightly yellowish and particle-free.

If any type of precipitate is observed either in the vial or after dilution, the product should be disposed of in accordance with standard procedures for the disposal of cytotoxic agents.

Read the leaflet for the shelf life of the diluted product.

Irinotecanshould not be administered as a bolus intravenously or as an infusion with a duration of less than 30 minutes or more than 90 minutes.

Disposal

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