Leaflet: information for the user

Irinotecan Hikma 20 mg/ml concentrate for infusion solution EFG

Irinotecan, trihydrate hydrochloride

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

1. What isIrinotecan Hikmaand what it is used for

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

3. How to useIrinotecan Hikma

4. Possible side effects

5. Storage ofIrinotecan Hikma

6. Contents of the pack and additional information

Irinotecán Hikma is a cancer medication that contains the active ingredient 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 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 worsened after initial therapy with fluorouracil.

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No use Irinotecán Hikma:

• If you are allergic to irinotecan hydrochloride trihydrate or any of the other components of this medication (listed in section 6).
• If you have chronic inflammatory bowel disease and/or intestinal obstruction.
• If you are breastfeeding (see section 2).
• If your bilirubin level is greater than 3 times the upper limit of the normal range. If you have severe bone marrow failure. If your overall health status is poor (WHO performance status greater than 2).
• If you are taking or have recently taken a medicinal plant called St. John's Wort (a herbal extract containing Hypericum perforatum).
• If you are to receive or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, flu) and for 6 months after chemotherapy.

If you receive irinotecan in combination with other medications, make sure to also read the prospectus of the other medications regarding additional contraindications.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Irinotecán Hikma:

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

Be especially careful with irinotecan. The use of irinotecan should be limited to specialized units for the administration of cytotoxic chemotherapy and should be administered only under the supervision of a qualified doctor in the use of anticancer chemotherapy.

Diarrea

Irinotecan may cause diarrhea, which in some cases can be severe. This may start a few hours or a couple of days after the infusion of the medication. If not treated, it can lead to dehydration and severe chemical imbalances, which can be fatal. Your doctor will prescribe a medication to help prevent or control this side effect. Make sure to acquire the medication immediately to have it at home when you need it.

-Take the medication as told by your doctor with the first sign of loose stools or frequent defecation.

-Drink a lot of water and/or salty drinks (water with gas, soda, or soup).

-Call your doctor or nurse if you still have diarrhea, especially if it lasts more than 24 hours, or if you feel dizzy, nauseous, or faint.

Neutropenia (decrease in some white blood cells)

This medication may decrease the white blood cell count, mainly in the weeks following the administration of the medication. This may increase the risk of infection. Make sure to inform your doctor or nurse immediately if you have any signs of infection, such as fever (38°C or higher), chills, painful urination, new cough, or sputum.

Haematological control

Your doctor may perform blood tests before and during treatment to control the effects of the medication on the blood count or blood biochemistry. According to the results of the analysis, you may need medications to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medication, or even stop it completely. Keep all your doctor's appointments and laboratory tests.

This medication may reduce the platelet count in the weeks following administration, 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 medications containing 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, tarry stools.

Nauseas and vomiting

You may have nausea and vomiting on the day you receive this medication or in the first few days after. Your doctor may give you medications before your treatment to help prevent nausea and vomiting. It is likely that your doctor will prescribe anti-nausea medications that you can take at home. Have these medications on hand when you need them. Call your doctor if you cannot take liquids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

This medication may affect the part of your nervous system that controls bodily secretions, leading to the so-called 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 medications that can help control them.

Pulmonary disorders

In rare cases, people who take this medication have severe lung problems. Inform your doctor immediately if you develop a cough or if it worsens, difficulty breathing, and fever. Your doctor may need to suspend your treatment to treat this problem.

This medication may increase the risk of large blood clots in the veins of the legs or lungs, which may move 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

Contact your doctor if you have abdominal pain and constipation, especially if you also have swelling and loss of appetite.

Radiation therapy

If you have recently received pelvic or abdominal radiation therapy, you may have a higher risk of developing bone marrow suppression. Talk to your doctor before starting treatment with irinotecan.

Renal function

Cases of renal dysfunction have been reported.

Cardiovascular disorders

Inform your doctor if you have or have had a heart disease or if you have previously received cancer medications. Your doctor will closely monitor you and discuss how to reduce risk factors (e.g., smoking, high blood pressure, and high fat content).

Vascular disorders

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

Other

This medication may cause mouth ulcers or lip ulcers, often in 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 how you brush your teeth. If necessary, your doctor may prescribe pain medications.

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 medication if you plan to undergo surgery or any procedure.

If you are taking this medication in combination with other cancer medications for your disease, make sure to also read the prospectus of the other medications.

If your doctor has told you that you have an intolerance to some sugars, contact your doctor before using this medication.

Other medications and irinotecan:

Irinotecan Hikma may interact with several medications and supplements, which may increase or decrease the level of the medication in your blood. Inform your doctor or pharmacist if you are taking, have taken recently, or may take any of the following:

• Medications used to treat epilepsy (carbamazepine, phenobarbital, phenytoin, and fosphenytoin)
• Medications used to treat fungal infections (ketoconazole, itraconazole, voriconazole, and posaconazole)
• Medications used to treat bacterial infections (clarithromycin, erythromycin, and telithromycin)
• Medications used to treat tuberculosis (rifampicin and rifabutin)
• St. John's Wort (a dietary supplement based on plants)
• Live attenuated vaccines
• Medications used to treat HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• Medications to suppress your immune system to prevent rejection in transplants (ciclosporin and tacrolimus)
• Medications used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamida)
• Anticoagulants (common anticoagulants, such as warfarin)
• Medications used to relax muscles during general anesthesia and surgery (suxamethonium)
• 5-Fluorouracil/folic acid
• Bevacizumab (an inhibitor of blood vessel growth)

Cetuximab (an inhibitor of the epidermal growth factor receptor)

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

While you are being treated with irinotecan, do not start or stop taking any medication without consulting your doctor first.

This medication may cause severe diarrhea. Try to avoid using laxatives and stool softeners while using this medication.

You may have other medications that interact with irinotecan. Consult your doctor, pharmacist, or nurse about your other medications, herbal products, and supplements, and if alcohol may cause problems with this medication.

Contraception, pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Contraception

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

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

Pregnancy

This medication 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 medication.

Breastfeeding

Irinotecan and its metabolite were measured in breast milk. Breastfeeding should be suspended during treatment with this medication.

If you are breastfeeding, consult your doctor or pharmacist before using this medication.

Fertility

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

Driving and operating machines

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

This medication contains sorbitol

This medication contains a sugar (sorbitol). Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disease, you should not receive this medication. Patients with HFI cannot break down fructose, which may cause severe side effects.

You must inform your doctor before receiving this medication if you (or your child) have HFI or if your child cannot take sugary foods or drinks because they feel nauseous, vomit, or experience unpleasant effects such as bloating, stomach cramps, or diarrhea.

This medication contains sodium

This medication contains less than 1 mmol (23 mg) of sodium per dose, making it essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor again.

Irinotecán will be administered by healthcare professionals.

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

Some people are genetically more prone to having some side effects of the medication.

The amount of irinotecán you will receive depends on many factors, including your height and weight, your overall health status or other health problems, and the type of cancer or disease you have.

Your doctor will determine your dose and treatment schedule. Irinotecán is injected into a vein by intravenous (IV) route. You will receive this injection in a clinic or hospital. Irinotecán 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 receiving irinotecán. You may need to continue taking these medications for at least one day after your irinotecán injection.

Inform your caregivers if you feel burning, pain, or swelling around the intravenous needle when irinotecán is injected. If the medication leaks out of the vein, it may cause damage to the tissues. If you feel pain or notice redness or swelling at the injection site while receiving irinotecán, inform your healthcare professional immediately.

Currently, several treatment regimens are recommended for irinotecán. Generally, it is administered once every 3 weeks (irinotecán administered alone) or once every 2 weeks (irinotecán administered in combination with chemotherapy with 5FU/AF). The dose will depend on several factors, including the treatment regimen, your body size, age, and overall health status, your blood counts, liver function, if you have received radiation in the abdomen or pelvis, and if you have any side effects, such as diarrhea.

Only your doctor can assess the duration of treatment.

If you use more Irinotecán Hikma than you should

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount administered.

If you forgot to use Irinotecán Hikma

Consult with your doctor for instructions if you miss a scheduled injection of irinotecán.

If you have any other questions about the use of this medication, ask 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. Contact your doctor immediately if you experience any of the following serious side effects (see section 2).

Seek emergency medical attention 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: starts within 24 hours after receiving this medicine, and is accompanied by symptoms such as: runny nose, increased salivation, tearing of the eyes, sweating, flushing, abdominal cramps (this may occur while the medicine is being administered. In this case, inform your healthcare professional immediately. Medications to stop and/or reduce this early side effect may be administered).

-Late diarrhea: starts more than 24 hours after receiving this medicine. Due to dehydration and electrolyte imbalance with diarrhea, it is essential to be in contact with healthcare professionals for control and to obtain recommendations on medications and diet modifications.

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 diarrhea with blood (which may be associated with abdominal pain or fever), produced by a bacteria called Clostridium difficile.

-Blood infection.

-Dehydration (due to diarrhea and vomiting).

-Orthostatic hypotension, tachycardia, and pallor (a condition called hypovolemia).

-Allergic reactions.

-Transient speech disorders during or shortly after treatment.

-Tickling.

-High blood pressure (during or after infusion).

-Cardiac problems*.

-Pulmonary disease that produces wheezing and difficulty breathing (see section 2).

-Hypophagia.

-Intestinal obstruction.

-Colon enlargement.

-Intestinal hemorrhage.

-Colitis.

-Abnormal laboratory test results.

-Intestinal perforation.

-Fatty liver.

-Dermatological reactions.

-Reactions at the injection site.

-Low potassium levels in the blood.

-Low sodium levels in the blood, mainly related to diarrhea and vomiting.

-Muscle cramps.

-Renal problems*.

-Low blood pressure*.

-Fungal infections.

-Viral infections.

* 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 reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting adverse reactions, 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 store at a temperature above 25°C.

Do not refrigerate or freeze.

Keep in the original packaging to protect it from light.

For single use only.

After dilution with 5% glucose, chemical and physical stability has been confirmed for use over 24 hours when stored between 2°C and 8°C and for 12 hours when stored below 25± 2°C, protected from light.

After dilution with 0.9% sodium chloride, chemical and physical stability has been confirmed for use over 24 hours when stored between 2°C and 8°C and for 12 hours when stored below 25± 2°C, protected from light.

Irinotecán Hikma must be diluted and used immediately after opening.

From a microbiological standpoint, the medication must be used immediately after the first opening. If not, the time and storage conditions of the medication in use before administration will be the responsibility of the user.

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

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacisthow to dispose ofthepackaging and themedicines that you no longerneed.This will help protect the environment.

Composition of Irinotecan Hikma

The active ingredient is irinotecan hydrochloride, trihydrate.

One milliliter of concentrate contains 20 mg of irinotecan hydrochloride trihydrate (equivalent to 17.33 mg of irinotecan).

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

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

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

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

The other components are sorbitol (E420), sodium hydroxide and/or hydrochloric acid (to adjust the pH to 3.5) and water for injection preparations.

Appearance of the product and packaging contents

Amber glass vials with FluoroTec or equivalent rubber stopper and aluminum flip-off cap.

Irinotecan Hikma is a yellow and transparent solution.

pH: 3.0 – 4.0

Osmolality: 265-320 mosmol/kg

Packaging sizes:

Packaging with 1 vial of 2 ml.

Packaging with 1 vial of 5 ml.

Packaging with 1 vial of 15 ml.

Packaging with 1 vial of 25 ml.

Only some packaging sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, nº 8, 8A – 8B

Fervença

2705 – 906 Terrugem SNT

Portugal

Tel: +351 21 980 84 10

e-mail: portugalgeral@hikma.com

Manufacturer responsible

Thymoorgan Pharmazie GmbH

Schiffgraben 23

D-38690 Goslar

Germany

Tel. +49 (0) 5324 7701-0

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area with the following names:

Germany: Irinotecan Hikma 20 mg/ml Concentrate for the preparation of an infusion solution

Austria: Irinotecan Hikma 20 mg/ml Concentrate for the preparation of an infusion solution

Belgium: Irinotecan Hikma 20 mg/ml

Spain: Irinotecán Hikma 20 mg/ml Concentrate for Solution for Infusion EFG

France: Irinotecan Hikma 20 mg/ml, solution to be diluted for infusion

Italy: Irinto 20mg/ml Concentrate for Solution for Infusion

Netherlands: Irinotecan HCl trihydrate Hikma 20 mg/ml concentrate for solution for infusion

Portugal: Irinotecano Hikma

United Kingdom (Northern Ireland): Irinotecan 20mg/ml Concentrate for solution for infusion

Last review date of this leaflet: October 2024

For detailed and updated information about this medicine, please visit 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:

Irinotecan Hikma 20mg/ml concentrate for solution for infusion

Irinotecan hydrochloride, trihydrate

Handling

Like other antineoplastic/cytotoxic agents, irinotecan must be prepared and handled with caution. It is mandatory to use safety glasses, a mask, and gloves.

In case of skin contact, wash the affected area with plenty of water and soap. In case of mucous membrane contact, wash the affected area thoroughly with water.

Instructions for dilution:

Like other injectable medications, the irinotecan solution must be prepared in aseptic conditions.

If any type of precipitate is observed, either in the vial or after reconstitution, the product must be eliminated in accordance with standard procedures for the elimination of cytotoxic agents.

Using a graduated syringe, remove the necessary amount of Irinotecan Hikma concentrate for solution from the vial, in an aseptic manner, and inject it into a 250 ml infusion bag or bottle. The infusion must be mixed carefully by manual rotation.

Instructions for protection during the preparation of the dilution:

The preparation must be performed in a safety cabinet using gloves and protective clothing (preferably under a vertical air system). The work area must be protected with disposable absorbent paper and plastic. Safety glasses, a hood, a lab coat, gloves, and disposable masks must be used.

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

In case of spills, use personal protective equipment. Broken glass must be collected and placed in containers for PATHOGENIC WASTE. Surfaces contaminated with the spill must be washed with plenty of water. After washing the surfaces, they must be carefully cleaned with a cloth that must be disposed of as HAZARDOUS WASTE.

In case of skin contact with irinotecan, place the affected area under a stream of water for some time and then wash it with water and soap. If mucous membrane contact occurs, wash the affected area thoroughly with water. If you experience any discomfort, consult a doctor.

If irinotecan comes into contact with the eyes, wash them thoroughly with plenty of water. Immediately contact an ophthalmologist.

Disposal:
All materials used for dilution and administration must be disposed of in accordance with the established procedures in the hospital for cytotoxic agents.