IRINOTECAN QILU 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Irinotecan Qilu 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 experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Irinotecan Qilu and what is it used for
2. What you need to know before you are given Irinotecan Qilu
3. How Irinotecan Qilu will be given to you
4. Possible side effects
5. Storing Irinotecan Qilu
6. Contents of the pack and other information

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

It is an anticancer medicine whose active substance is irinotecan hydrochloride 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 colon or rectal cancer in adults, in combination with other medicines (e.g., 5-fluorouracil/folinic acid, bevacizumab, cetuximab, capecitabine).

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

2. What you need to know before you are given Irinotecan Qilu

Do not use Irinotecan Qilu:

• if you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6 «Contents of Irinotecan Qilu»).
• if you have chronic inflammatory intestinal 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 very low blood cell counts (severe bone marrow failure).
• if you have a poor state of health (evaluated greater than 2 according to the WHO).
• if you are taking or have recently taken St. John's Wort (a plant-based extract containing hypericum).
• if you are receiving or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, flu) and during the 6 months following the interruption of chemotherapy.

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with irinotecan. In the elderly population, more intense monitoring is necessary.

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

Diarrhea

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

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

Nausea and vomiting

If you have nausea or vomiting on the day you receive the medicine or in the first few days after administration. Your doctor may give you a medicine before treatment to prevent nausea and vomiting. They may also prescribe anti-nausea medicines that you can take at home. Have them on hand for when you need them. Call your doctor if you cannot take fluids due to nausea and vomiting.

Neutropenia (Decreased white blood cell count)

Irinotecan can cause a decrease in the number of certain types of white blood cells, mainly in the weeks that play an important role in fighting infections. This is called neutropenia. Neutropenia is usually seen during treatment with irinotecan 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 being around 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.

Blood test monitoring

Your doctor will likely have a blood test done before and during treatment to check the effects of the medicine on blood counts or blood chemistry. Based on the results, you may need medicines to help treat the 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, which increases 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 bruising or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black and tarry stools.

Acute cholinergic syndrome

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

Pulmonary disorders

People who receive this medicine rarely have severe pulmonary 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 warmth in an arm or leg.

Inflammationof the intestines and intestinal obstruction

Call your doctor if you feel stomach pain and cannot defecate, especially if you also have bloating or 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 receiving Irinotecan Qilu.

Kidney problems

Renal dysfunction has been reported.

Heart problems

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

Vascular disorders

Irinotecan is rarely associated with vascular disorders (blood clots in the legs and arms) that may occur in patients with multiple risk factors.

Others

This medicine may cause sores in the mouth or lips, often in the first few 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 brush your teeth. If needed, your doctor will prescribe pain medicines.

If you need information on contraceptives and breastfeeding, see the information provided in the Contraception, pregnancy, breastfeeding, and fertility section.

Tell your doctor or dentist that you are receiving this medicine if you are scheduled 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 package leaflets of each of these medicines.

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

Other medicines and Irinotecan Qilu

Irinotecan may interact with a number 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 recently taken, or may take any other medicine, such as:

• carbamazepine, phenobarbital, phenytoin, or fosphenytoin (used to treat 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 plant-based remedy)
• vitamin K antagonists (e.g., warfarin, used to reduce blood clot formation)
• live attenuated vaccines
• cyclosporine and tacrolimus (used to reduce the activity of the immune system, e.g., after organ transplantation to prevent rejection)
• regorafenib, crizotinib, idelalisib, and apalutamide (used to treat cancer)
• suxamethonium (used to relax muscles during general anesthesia and surgery)
• 5-fluorouracil/folinic acid
• bevacizumab (a vascular endothelial growth factor inhibitor)
• cetuximab (an epidermal growth factor receptor inhibitor)

Talk to your doctor, pharmacist, or nurse before receiving irinotecan if you are currently 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 whether alcohol can 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.

In the case of men, they must use effective contraceptive methods during and up to 3 months after finishing treatment. It is essential that you discuss with your doctor the types of contraceptives you can use with this medicine.

Pregnancy

The medicine may cause problems to the fetus if taken at the time of 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.

Breastfeeding

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

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

Fertility

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

Driving and using machines

During the first 24 hours after administration of irinotecan, you may feel dizzy or experience vision changes. If you experience these effects, avoid driving vehicles or using machines.

Irinotecan Qilu contains sorbitol

This medicine contains sugar (sorbitol). Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you cannot 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) have HFI or if your child can no longer take sweet foods or drinks because they make them 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.

Irinotecan Qilu contains sodium

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

3. How to use Irinotecan Qilu

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

Irinotecan will be administered to you 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 certain side effects from the medicine.

The amount of irinotecan you receive depends on many factors, including your weight and height, your overall health, 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 determine the dose and treatment schedule.

Irinotecan is injected into a vein by intravenous (IV) infusion. 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 medicines to prevent nausea, vomiting, diarrhea, and other side effects during the injection of irinotecan. You may need to continue taking these medicines for at least one day after the infusion of irinotecan.

Tell your caregivers if you feel burning, pain, or swelling around the needle during the injection of irinotecan. The medicine can damage tissues if it leaks out of the vein. If you feel pain or notice redness or swelling at the injection site while receiving irinotecan, inform a healthcare professional immediately.

Several treatment schedules are currently recommended for irinotecan. It is usually administered every three weeks (irinotecan given alone) or once every two weeks (irinotecan given in combination with chemotherapy with 5-fluorouracil/folinic acid). The dose will depend on a number of factors, including the treatment schedule, your body size, age, and overall health, your blood counts, liver function, whether you have received radiation to the abdomen or pelvis, and whether you have any side effects such as diarrhea.

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

Only your doctor can determine the duration of treatment.

If you use more Irinotecan Qilu than you should

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

If you miss a dose of Irinotecan Qilu

Call your doctor to find out what to do if you miss an appointment for the injection 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 can cause adverse effects, although not all people suffer from them. Your doctor will inform you about these adverse effects and explain the risks and benefits of treatment.

Some of these adverse effects should be treated immediately(see also the section Warnings and Precautions).

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

• Allergic reactions: hives, difficulty breathing, swelling of the face, lips, tongue, or throat.
• diarrhea (see section 2)
• Early diarrhea: within 24 hours after administration of the medicine, accompanied by symptoms such as runny nose, increased salivation, watery eyes, sweating, hot flashes, and abdominal cramps. (This may occur while the medicine is being administered. If this is the case, notify the healthcare professional in charge without delay. There are medicines that you may receive to stop or alleviate this early adverse effect).
• Late diarrhea: occurrence more than 24 hours after receiving the medicine. Due to the possibility of dehydration and electrolyte imbalance caused by diarrhea, it is essential to stay in touch with healthcare professionals to be monitored and receive advice on possible medication and dietary changes.

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

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

† Frequent: may affect up to 1 in 10 people

Unknown frequency: cannot be calculated from available data

• Severe, persistent, or bloody diarrhea (which may be associated with stomach pain or fever) caused by a bacterium called (Clostridium difficile)
• Blood infection
• Dehydration (due to diarrhea and vomiting)
• Dizziness, rapid heartbeat, pale skin (a condition called hypovolemia)
• Allergic reaction
• Transient speech disturbances during or immediately after treatment
• Pinch
• Increased blood pressure during and after administration
• Heart problems*
• Lung disease characterized by difficult breathing, dry cough, or difficulty breathing
• Hiccup
• Partial or complete intestinal obstruction (intestinal obstruction, ileus)
• Dilated colon
• Intestinal bleeding
• Inflammation of the large intestine
• Abnormal test results
• Perforation in the intestine
• Fatty liver disease
• Skin reactions
• Reactions at the site of administration of the medicine
• Decreased blood levels of potassium and sodium, most of which are related to diarrhea and vomiting
• Muscle contractions or cramps and numbness (paresthesia)
• Kidney problems (renal failure)*
• Low blood pressure*
• Fungal infections
• Viral infections

Rare 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 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 is not listed in this prospectus. 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 Qilu

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

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

Store below 25°C.

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

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 Qilu

• The active ingredient is irinotecan 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 Package Contents

The 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 boxes of a single brown glass vial.

Presentation:

1 vial of 2 ml

1 vial of 5 ml

1 vial of 15 ml

1 vial of 25 ml

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

QILU PHARMA SPAIN S.L.,

Paseo de la Castellana 40, 8th floor,

Madrid, 28046,

Spain

Manufacturer

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 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 prospectus:February 2022

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:

Irinotecan 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. The dilution should be performed by properly trained personnel, under aseptic conditions, and in an area designated for this purpose. Extreme caution should be taken to avoid contact with the skin and mucous membranes.

Protection instructions for the preparation of Irinotecan Qilu concentrate for solution for infusion EFG:

1. A protective hood and protective gloves should be used, as well as a protective gown. If a protective hood is not available, a mask and protective glasses should be used.
2. Empty containers, as well as injectable vials and infusion bottles, cannulas, syringes, catheters, used tubes, and residues of the cytostatic drug should be treated as hazardous waste and their disposal should be carried out in accordance with local guidelines for handling HAZARDOUS WASTE.
3. In the event of a spill, follow these instructions:

• Protective clothing should be worn.
• Broken crystals should be collected and placed in the HAZARDOUS WASTE container.
• Contaminated surfaces should be rinsed thoroughly with plenty of cold water.
• Then, the rinsed surfaces should be cleaned completely, and the materials used in the cleaning should be discarded as HAZARDOUS WASTE.
• 1. In the event that irinotecan comes into contact with the skin, rinse the affected area with plenty of water and then wash with soap and water. In the event of contact with the mucous membranes, rinse the exposed area with plenty of water. If you experience any discomfort, contact a doctor.
  2. In the event that irinotecan comes into contact with the eyes, rinse them thoroughly with plenty of water and contact an ophthalmologist 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. Remove the necessary amount of irinotecan concentrate from the vial with a calibrated syringe and under aseptic conditions, and inject it into a 250 ml capacity infusion bag or bottle. Mix the infusion solution thoroughly by rotating the bag or bottle by hand.

If a precipitate is observed in the vials or after reconstitution, the product should be discarded following the standardized procedures for the elimination of cytostatics.

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

Elimination

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