Leaflet: information for the user

Irinotecan Qilu 20 mg/ml concentrate for infusion 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 kind of side effect, consult your doctor, pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. See section4.

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

2. What you need to know before they start administering Irinotecan Qilu

3. How they will administer Irinotecan Qilu

4. Possible side effects

5. Storage of Irinotecan Qilu

6. Contents of the container and additional information

It is a cancer medication whose active ingredient isirinotecanhydrochloride trihydrate.

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

It is used in the treatment of advanced or metastatic colorectal cancer in adults, in combination with other medications (for example, 5-fluorouracil/leucovorin, bevacizumab, cetuximab, capecitabine).

Irinotecan may be used as monotherapy in patients with metastatic colorectal cancer whose disease has recurred or worsened after initial treatment with fluorouracil.

No use Irinotecán Qilu:

• if you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6 "Irinotecán Qilu Contents").
• if you have chronic inflammatory bowel disease and/or intestinal obstruction.
• if you are a breastfeeding woman (see section 2).
• if you have a bilirubin concentration greater than 3 times the upper limit of normal.
• if you have severe bone marrow insufficiency (low white blood cell count).
• if you have a poor general health condition (evaluated as more than 2 according to the WHO).
• if you are taking or have recently taken St. John's Wort (a herbal extract containing hypericum).
• if you are receiving or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, flu) and for the 6 months following the end of chemotherapy.

If you are given irinotecan in combination with other medicines, make sure to also read the leaflet for each of these medicines, especially the section on additional contraindications.

Warnings and Precautions:

Consult your doctor, pharmacist or nurse before starting to use irinotecan. In the elderly population, more intensive monitoring is required.

Be particularly careful with Irinotecán Qilu. The use of irinotecan should be restricted to specialized units for the administration of cytotoxic chemotherapy, and it should only be administered under the supervision of a specialist medical practitioner in the use of antineoplastic chemotherapy.

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

Diarrea:

Irinotecan may cause diarrhea that could be severe in some cases. It may start a few hours or a couple of days after the infusion. Without treatment, it could lead to dehydration and severe chemical imbalances that can be life-threatening. Your doctor will prescribe a medicine to help you prevent or control this side effect. Make sure to get the medicine immediately to have it at home available when you need it.

• Take the medicine as prescribed at the first sign of soft stools or more frequent bowel movements.
• Drink large amounts of water and (or) salty drinks (soda, juice or soup).
• Call your doctor or nurse if the diarrhea persists, especially if it lasts more than 24 hours or if you feel dizzy or lightheaded, or if you faint.

Náuseas and Vómitos:

If you have nausea or vomiting on the day you receive the medicine or in the first days after administration. Your doctor may give you some medicine before treatment to prevent nausea and vomiting. They may prescribe anti-nausea medicines that you can take at home. Keep them handy when you need them. Call your doctor if you cannot drink liquids due to nausea and vomiting.

Neutropenia (Decrease in White Blood Cell Count):

Irinotecan may cause a decrease in the number of certain types of white blood cells, mainly in the weeks when they play an important role in fighting infections. This is known as neutropenia. Neutropenia usually occurs during irinotecan treatment and is reversible.

Make sure to inform your doctor or nurse if you have any signs of infection such as fever (38°C or higher), chills, pain when urinating, a new cold or phlegm. Avoid staying near people who are sick or have infections. Inform your doctor immediately if you develop signs of infection.

Inform your doctor immediately if you develop signs of infection.

Control of Hemogram:

Your doctor will likely do a blood test before and during treatment to check the effects of the medicine on blood counts or blood chemistry. Depending on the results, you may need medicines to help treat the side effects. Your doctor may also need to reduce or delay the next dose of the medicine, or even stop it. Do not miss any appointments with your doctor or laboratory tests.

This medicine may reduce the platelet count in the weeks following administration, increasing the risk of bleeding. Talk to your doctor before taking any medicine or supplement that could affect the 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, tar-like stools.

Síndrome colinérgico agudo:

This medicine may affect the part of the nervous system that controls secretions, and lead to what is known as acute cholinergic syndrome. Symptoms include nasal discharge, increased saliva, excessive tears in the eyes, sweating, hot flashes, 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.

Trastornos pulmonares:

People who receive this medicine rarely have severe lung problems. Inform your doctor immediately if you have a new cough or if it worsens, difficulty breathing, and fever. Your doctor may need to interrupt treatment to treat this problem.

This medicine may increase the risk of blood clots in the veins of the legs or lungs that can move to other parts of the body such as the lungs or brain. Inform your doctor immediately if you feel chest pain, shortness of breath, swelling, pain, redness, or heat in an arm or leg.

Inflamación intestinal crónica y bloqueo intestinal:

Call your doctor if you feel stomach pain and cannot defecate, especially if you also have swelling or loss of appetite.

Tratamiento de irradiación:

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 they administer Irinotecán Qilu.

Insuficiencia renal:

Renal dysfunction has been reported.

Trastornos cardíacos:

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

Trastornos vasculares:

Irinotecan is rarely associated with vascular disorders (blood clots in the veins and arteries) that may occur in patients with several risk factors.

Otros:

This medicine may cause mouth sores or lip sores, often in the first weeks after treatment. This can cause pain and bleeding in the mouth, and even make it difficult to eat. Your doctor or nurse may suggest ways to reduce these discomforts, such as changing the way you eat or brushing your teeth. If you need it, your doctor will prescribe pain medicines.

Si necesita información sobre anticoncepción y lactancia, consulte la información facilitada en la sección Anticoncepción, embarazo, lactancia y fertilidad.

Inform your doctor or dentist that you are receiving this medicine if you are planning to undergo surgery or a procedure.

If you are given irinotecan in combination with other anticancer medicines for your condition, make sure to also read the leaflets for each of these medicines.

If your doctor has informed you that you have intolerance to any sugar, consult your doctor before taking this medicine.

Otros medicamentos e Irinotecán Qilu:

Irinotecan may interact with a series of medicines and supplements, which may increase or decrease the level of the medicine in the blood. Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine such as:

• carbamazepine, phenobarbital, phenytoin, or fosphenytoin (used in the treatment of seizures and epilepsy).
• ketoconazole, itraconazole, voriconazole, and posaconazole (used to treat fungal infections).
• clarithromycin, erythromycin, and telithromycin (used to treat bacterial infections).
• rifampicin and rifabutin (used to treat tuberculosis).
• atazanavir, indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, and others (used to treat HIV infection).
• St. John's Wort, (a herbal remedy based on plants).
• antagonists of vitamin K (e.g., warfarin, used to reduce blood clotting).
• live attenuated vaccines
• ciclosporin and tacrolimus (used to reduce the activity of the immune system, for example, after an organ transplant to prevent rejection).
• regorafenib, crizotinib, idelalisib, and apalutamida (used to treat cancer).
• suxamethonium (used to relax muscles, and during general anesthesia and surgery).
• 5-fluorouracil/acid folinic
• bevacizumab (an inhibitor of blood vessel growth)
• cetuximab (an inhibitor of the EGF receptor)

Talk to your doctor, pharmacist, or nurse before receiving irinotecan if you are already undergoing or have recently undergone chemotherapy (and radiation therapy).

Do not start or stop taking any medicine while receiving irinotecan without consulting your doctor first.

This medicine may cause severe diarrhea. Avoid taking laxatives and stool softeners while receiving this medicine.

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

Anticoncepción, embarazo, lactancia y fertilidad:

Anticoncepción:

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

Men should use effective contraceptive methods during and for 3 months after completing treatment. It is essential to discuss with your doctor the types of contraceptives you can use with this medicine.

Embarazo:

The medicine may cause problems for the fetus if taken 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 receiving this medicine.

Lactancia:

Irinotecan and its metabolites are excreted in breast milk. You should stop breastfeeding during the duration of treatment with this medicine.

If you are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Fertilidad:

No studies have been conducted, however, this medicine may affect fertility. Talk to your doctor before taking this medicine about the possible risks of it and about the possible effects on your reproductive capacity.

Conducción y uso de máquinas:

During the first 24 hours after receiving irinotecan, you may feel dizzy or experience visual disturbances. If you experience these effects, avoid driving vehicles or using machines.

Irinotecán Qilu contiene sorbitol:

This medicine contains sugar (sorbitol). Sorbitol is a source of fructose. If you (or your child) suffer from hereditary fructose intolerance (HFI), a rare genetic disorder, you will not be able to receive this medicine. Patients with HFI cannot break down fructose, which can cause severe side effects.

Before receiving this medicine, you must inform your doctor if you (or your child) suffer from HFI or if your child can no longer take sweet foods or drinks because they feel unwell, vomit, or develop uncomfortable effects such as bloating, stomach cramps, or diarrhea.

This medicine contains 45 mg of sorbitol per mL, which is equivalent to 90 mg/2 mL, 225 mg/5 mL, 675 mg/15 mL, and 1,125 mg/25 mL.

Irinotecán Qilu contains sodium:

This medicine contains less than 1 mmol of sodium (23 mg) per vial, which is essentially "sodium-free".

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

Irinotecan will be administered by a doctor or nurse.

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

Some people are genetically more prone to having some adverse effects from the medication.

The amount of irinotecan you receive depends on many factors, including your weight and height, your overall health status or other health problems, and the type of cancer or disease being treated. It will also depend on other treatments you may have received to treat the cancer you have. Your doctor will establish the dose and treatment schedule.

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

You may receive other medications to prevent nausea, vomiting, diarrhea, and other adverse effects during the injection of 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 needle during the injection of irinotecan. The medication can damage tissues if it leaks out of the vein. If you feel pain or observe redness or swelling at the injection site while receiving irinotecan, notify a healthcare professional immediately.

Several treatment regimens are currently recommended for irinotecan. Typically, it is administered every three weeks (irinotecan administered alone) or once every two weeks (irinotecan administered in combination with chemotherapy with 5-fluorouracil/leucovorin). The dose will depend on a series of factors, including the treatment schedule, your body size, age, and overall health status, your blood counts, liver function, whether you have received radiation in the abdomen or pelvis, and if you have any adverse effects such as diarrhea.

Your doctor may adjust these dosing regimens based on your condition and any adverse effects you may experience.

Only yourdoctorcan assess the duration of treatment.

If you use more Irinotecan Qilu than you should

Irinotecan will be administered by a doctor or nurse who are familiar with this type of treatment, so the likelihood of you receiving an overdose is very small.

If you did not receive a dose of Irinotecan

Call your doctor to find out what to do if you miss a scheduled injection of irinotecan.

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. Your doctor will inform you about these side effects and explain the risks and benefits of treatment.

Some of these side effects require immediate treatment(also see the sectionWarnings and Precautions).

Seek emergency medical assistance if you experience any of the following signs of an allergic reaction: urticaria,

•allergic reactions: urticaria, difficulty breathing, facial swelling, lips, tongue, or throat swelling.

•diarrhea (see section 2)

•early diarrhea: within 24 hours of medication administration, accompanied by symptoms such as runny nose, increased salivation, watery eyes, sweating, hot flashes, and abdominal cramps. (This may occur while taking the medication. If so, notify your healthcare provider promptly. There are medications you can receive to stop or alleviate this early side effect).

•late diarrhea: occurrence more than 24 hours after receiving the medication. Due to the possibility of dehydration and electrolyte imbalance caused by diarrhea, it is essential to maintain contact with healthcare professionals for monitoring and receive guidance on possible medication and dietary changes.

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

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

† Common: may affect up to 1 in 10people

Unknown frequency: cannot be calculated from available data

• Severe, persistent, or bloody diarrhea (possibly associated with stomach pain or fever) caused by a bacteria called (Clostridium difficile)
• Blood infection
• Dehydration (due to diarrhea and vomiting)
• Mild dizziness, rapid heartbeat, pale skin (a condition called hypovolemia)
• Allergic reaction
• Temporary speech changes during or shortly after receiving treatment
• Pinch marks
• Increased blood pressure during administration and after
• Cardiac problems*
• Pulmonary disease that manifests with difficult breathing, dry cough, or difficulty breathing
• Hypophagia
• Partial or complete intestinal obstruction (intestinal obstruction, ileus)
• Colon dilation
• Intestinal hemorrhage
• Long intestine inflammation
• Abnormal test results
• Intestinal perforation
• Fatty liver disease
• Cutaneous reactions
• Reactions at the site of medication administration
• Decreased blood potassium and sodium concentrations, most of which are related to diarrhea and vomiting
• Muscle cramps and numbness (paresthesia)
• Renal problems (renal insufficiency)*
• Low blood pressure*
• Fungal infections
• Viral infections

Cases of these events have been observed in patients who had experienced episodes of dehydration due to diarrhea and/or vomiting or blood infection.

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 prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Usewww.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial and the box after «CAD». The expiration date is the last day of the month indicated.

Store below 25º C.

Store in the original packaging to protect it from light. Do not refrigerate or freeze.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Irinotecan Qilu

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

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

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

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

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

• The other components are sorbitol (E-420), lactic acid, sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Appearance of the product and contents of the package

Irinotecan concentrate for solution for infusion is a clear, pale yellow aqueous solution.

Irinotecan 40 mg/2 ml, 100 mg/5 ml, 300 mg/15 ml, and 500 mg/25 ml are presented in brown glass vials in single-dose packs.

Presentations:

1 vial of 2 ml

1 vial of 5 ml

1 vial of 15 ml

1 vial of 25 ml

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

QILU PHARMA SPAIN S.L.,

Paseo de la Castellana 40, 8th floor,

Madrid, 28046,

Spain

Manufacturer responsible

KYMOS, S.L.

Ronda de Can Fatjó, 7B (Parque Tecnológico del Vallès),

Cerdanyola del Vallès, 08290

Barcelona, Spain

Local representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 – Barcelona

Spain

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

Last review date of this leaflet:February2022

More detailed and up-to-date information on this medicinal product is available on 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:

Irinotecán Qilu 20 mg/ml concentrate for solution for infusion EFG

irinotecan hydrochloride trihydrate

Instructions for use.-Cytotoxic.

Handling of irinotecan

As with all antineoplastics, extreme caution should be exercised when handling irinotecan. Dilution should be performed by a properly trained person, in aseptic conditions, and in a designated area. Extreme caution should be exercised to avoid contact with the skin and mucous membranes.

Instructions for protection for the preparation of Irinotecán Qilu concentrate for solution for infusion EFG:

• A protective gown should be worn.
• Broken glass should be collected and placed in the HAZARDOUS WASTE container.
• Contaminated surfaces should be thoroughly washed with cold water.
• After washing, the surfaces should be completely cleaned, and the materials used for cleaning should be disposed of as HAZARDOUS WASTE.
• 1. If irinotecan comes into contact with the skin, wash the affected area with plenty of water and then wash with soap and water. If irritation occurs, contact a doctor.
  2. If irinotecan comes into contact with mucous membranes, rinse the affected area with plenty of water. If irritation occurs, contact a doctor immediately.

Preparation of the infusion solution

The irinotecan concentrate for solution for infusion is indicated only for intravenous infusion, after prior dilution in the recommended diluents: 0.9% sodium chloride solution for infusion or 5% glucose solution for infusion. Extract the required amount of irinotecan concentrate from the vial using a calibrated syringe and in aseptic conditions, and inject it into a 250 ml infusion bag or bottle. Mix the infusion solution thoroughly by rotating the bag or bottle with your hand.

If any precipitate is observed in the vials or after reconstitution, the product should be discarded in accordance with the standard procedures for the disposal of cytostatics.

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

Elimination

All materials used in the 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.