IRINOTECAN AUROVITAS 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Irinotecan Aurovitas20 mg/ml concentrate for solution for infusion

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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Irinotecan Aurovitas is a cancer medicine that contains the active substance irinotecan hydrochloride trihydrate.

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

Irinotecan is indicated alone or in combination with other medicines for the treatment of patients with advanced or metastatic colon or rectal cancer.

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

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

Do not use Irinotecan Aurovitas

• If you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6).
• If you have a chronic inflammatory bowel disease or intestinal obstruction.
• If you are breastfeeding (see section 2).
• If your bilirubin level is more than 3 times the upper limit of the normal range.
• If you have severe bone marrow failure.
• If your general state of health is poor (WHO performance status greater than 2).
• If you are taking or have recently taken St. John's Wort (a plant-based extract containing Hypericum).
• 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 the end of chemotherapy.

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

Warnings and precautions

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

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

Diarrhea

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

• Take the medicine as your doctor has told you with the first sign of loose or frequent stools.
• Drink plenty of water and/or electrolyte-rich drinks (sparkling water, soda, or soup).
• Call your doctor or nurse if you still have diarrhea, especially if it lasts more than 24 hours, or if you are dizzy, faint, or pass out.

Neutropenia (decrease in some white blood cells)

This medicine can decrease the count of white blood cells, mainly in the weeks following administration of the medicine. This can 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, pain when urinating, new cough, or sputum. Avoid being near people who are sick or have infections. Inform your doctor immediately if you show signs of infection.

Blood tests

Your doctor will likely have blood tests done before and during treatment to monitor the effects of the medicine on your blood count or blood biochemistry. Based on the results of the tests, you may need medicines to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medicine, or even stop it altogether. Keep all your doctor's appointments and laboratory tests.

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

Nausea and vomiting

You may have nausea and vomiting on the day you receive this medicine or in the first few days after. Your doctor may give you medicines before your treatment to help prevent nausea and vomiting. You may be prescribed anti-nausea medicines to take at home. Have these medicines on hand for when you need them. Call your doctor if you cannot take fluids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

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

Lung disorders

Rarely, people taking this medicine 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 stop your treatment to treat this problem.

This medicine can increase the risk of serious blood clots in the veins of the legs or lungs, which can 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 warmth in an arm or leg.

Chronic intestinal inflammation and/or intestinal obstruction

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

Radiation therapy

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

Kidney function

There have been reports of kidney dysfunction.

Heart disorders

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

Vascular disorders

Irinotecan is rarely associated with circulation disorders (blood clots in the legs and lungs) and can occur rarely in patients with multiple risk factors.

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

Others

This medicine can cause mouth sores or lip sores, often in the first few weeks after starting treatment. This can cause mouth pain, bleeding, or even problems eating. Your doctor or nurse may suggest ways to reduce this, such as changing how you eat or how you brush your teeth. If necessary, your doctor may prescribe pain medicines.

For information on contraception and breastfeeding, see the information provided later in the section Contraception, pregnancy, breastfeeding, and fertility.

Inform your doctor or dentist that you are being treated with this medicine if you plan to undergo surgery or any procedure.

If you are using this medicine in combination with other cancer medicines for your disease, make sure to also read the package leaflet of the other medicines.

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

Other medicines and Irinotecan Aurovitas

Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

Irinotecan can interact with several medicines and supplements, which can increase or decrease the level of the medicine in your blood. Inform your doctor or pharmacist if you are using or have used any of the following medicines:

• Medicines used to treat epilepsy (carbamazepine, phenobarbital, phenytoin, and fosphenytoin).
• Medicines used to treat fungal infections (ketoconazole, itraconazole, voriconazole, and posaconazole).
• Medicines used to treat bacterial infections (clarithromycin, erythromycin, and telithromycin).
• Medicines used to treat tuberculosis (rifampicin and rifabutin).
• St. John's Wort (a plant-based dietary supplement).
• Live attenuated vaccines.
• Medicines used to treat HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others).
• Medicines used to suppress your immune system to prevent rejection in transplants (cyclosporine and tacrolimus).
• Medicines used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamide).
• Vitamin K antagonists (common anticoagulants, such as warfarin).
• Medicines used to relax muscles during general anesthesia and surgery (suxamethonium).
• 5-Fluorouracil/folinic acid.
• Bevacizumab (a vascular endothelial growth factor inhibitor).
• Cetuximab (an epidermal growth factor receptor inhibitor).

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

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

This medicine can cause severe diarrhea. Try to avoid using laxatives and stool softeners while using this medicine.

There may be more medicines that interact with irinotecan. Consult your doctor, pharmacist, or nurse about your other medicines, plant-based products, 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 an effective contraceptive method during and up to 6 months after the end of treatment.

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

Pregnancy

This medicine may cause harm to the fetus if used at the time of conception or during pregnancy. Before starting treatment, your doctor will make sure you are not pregnant.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Breastfeeding

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

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

Fertility

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

Driving and using machines

In the first 24 hours or so after administration of irinotecan, you may feel dizzy or have changes in vision. If you have these symptoms, do not drive or operate machinery.

Irinotecan Aurovitas contains sorbitol

This medicine contains sorbitol. Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you must not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Consult your doctor before receiving this medicine if you (or your child) have HFI or cannot take sweet foods or drinks because they cause dizziness, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhea.

Irinotecan Aurovitas contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to use Irinotecan Aurovitas

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If in doubt, consult your doctor again.

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 having some side effects of the medicine.

The amount of irinotecan you receive will depend on many factors, including your height and weight, your general state of health, or other health problems, and the type of cancer or disease you have. Your doctor will determine your dose and treatment schedule.

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

You may be given other medicines to prevent nausea, vomiting, diarrhea, and other side effects while you receive irinotecan. You may need to continue taking these medicines for at least one day after your irinotecan injection.

Inform your caregivers if you feel burning, pain, or swelling around the needle when irinotecan is injected. If the medicine leaks out of the vein, it can cause tissue damage. If you feel pain or notice redness or swelling at the injection site while receiving irinotecan, inform the healthcare professional immediately.

Several treatment schedules are currently recommended for irinotecan. It is usually administered once every 3 weeks (irinotecan given alone) or once every 2 weeks (irinotecan given in combination with 5FU/FA chemotherapy). The dose will depend on several factors, including the treatment schedule, your body size, age, and general 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.

Only your doctor can assess the duration of treatment.

If you use more Irinotecan Aurovitas than you should

Seek emergency medical attention. The symptoms of overdose may include some of the serious side effects listed in this leaflet.

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 medicine and the amount administered.

If you miss a dose of Irinotecan Aurovitas

Consult your doctor for instructions if you miss an appointment for your irinotecan injection.

Do not use a double dose to make up for missed doses.

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

4. Possible Adverse Effects

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

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

Seek emergency medical attention if you have any of these symptoms of an allergic reaction: hives; difficulty breathing; swelling of the face, lips, tongue, or throat.

• Diarrhea (see section 2).
• Early diarrhea: 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, quickly inform the healthcare professional. Medicines can be administered to stop and/or decrease this early adverse effect).
• Late diarrhea: starts more than 24 hours after receiving this medicine. Due to dehydration and electrolyte imbalance problems with diarrhea, it is essential to be in contact with healthcare professionals for control and to obtain recommendations on medications and dietary modifications.

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

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

† Frequent: may affect up to 1 in 10 people.

Unknown frequency (cannot be estimated from available data)

• Severe, persistent, and 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, and paleness (a condition called hypovolemia).
• Allergic reactions.
• Transient speech disorders during or shortly after treatment.
• Numbness.
• High blood pressure (during or after perfusion).
• Heart problems*.
• Lung disease that causes wheezing and difficulty breathing (see section 2).
• Hiccup.
• Intestinal obstruction.
• Colon enlargement.
• Intestinal bleeding.
• Inflammation of the large intestine.
• Abnormal laboratory test results.
• Intestinal perforation.
• Fatty liver.
• Skin reactions.
• Reactions at the administration site.
• Low potassium levels in the blood.
• Low salt levels in the blood, mainly related to diarrhea and vomiting.
• Muscle cramps.
• Kidney problems*.
• Low blood pressure.
• Fungal infections.
• Viral infections.

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, 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 Aurovitas

Keep this medicine out of sight and reach of children.

Do not freeze.

For single use.

Store the vial in the outer packaging to protect it from light.

Do not use this medicine after the expiration date shown on the carton, after EXP. The expiration date is the last day of the month indicated.

The product must be diluted and used immediately after opening.

If prepared under aseptic conditions, the diluted solution can be stored for 24 hours at a temperature below 30°C and for 48 hours between 2-8°C (i.e., in the refrigerator).

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 Aurovitas

• The active ingredient is irinotecan hydrochloride trihydrate.
• 1 ml of concentrate contains 20 mg of irinotecan hydrochloride trihydrate, equivalent to 17.33 mg of irinotecan.
• A 2 ml vial contains 40 mg of irinotecan hydrochloride trihydrate.
• A 5 ml vial contains 100 mg of irinotecan hydrochloride trihydrate.
• A 15 ml vial contains 300 mg of irinotecan hydrochloride trihydrate.
• A 25 ml vial contains 500 mg of irinotecan hydrochloride trihydrate.
• The other components are: sorbitol E420, lactic acid, sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Appearance of the Product and Package Contents

Irinotecan Aurovitas 20 mg/ml concentrate for solution for infusion is a clear, colorless or slightly yellowish solution.

Package Sizes:

1 vial of 2 ml

1 vial of 5 ml

5 vials of 5 ml

1 vial of 15 ml

1 vial of 25 ml

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

Or

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

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

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

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

Germany: Irinotecan Aurobindo 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Belgium: Irinotecan AB 20 mg/ml concentraat voor oplossing voor infusie

Spain: Irinotecán Aurovitas 20 mg/ml concentrado para solución para perfusión

France: IRINOTECAN ARROW 20 mg/ml, solution à diluer pour perfusion

Italy: Irinotican Aurobindo

Netherlands: Irinotecan Aurobindo 20 mg/ml, concentraat voor oplossing voor infusie

Portugal: Irinotecano Aurovitas

Date of the last revision of this prospectus: April 2022

Other Sources of Information

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

This information is intended only for healthcare professionals:

Instructions for Use

Cytotoxic

Handling of Irinotecan Aurovitas

Like other antineoplastic agents, irinotecan should be prepared and handled with caution. Dilution should be performed under aseptic conditions, by experienced personnel, in a specific area. Precautions should be taken to avoid skin and mucous membrane contact.

Safety instructions for the preparation of irinotecan solution for infusion:

1. A protective hood, as well as protective gloves and gown, should be used. If a protective hood is not available, protective glasses and a mask should be used.
2. Open containers, such as vials, infusion bottles, and cannulas, syringes, catheters, tubes used, and cytostatic residues, should be considered as hazardous waste and disposed of according to local regulations for the handling of HAZARDOUS WASTE.
3. In case of spillage, follow these instructions:
   • protective clothing should be worn.
   • broken glass should be collected and thrown away in a HAZARDOUS WASTE container.
   • contaminated surfaces should be rinsed thoroughly with plenty of cold water.
   • cleaned surfaces should be carefully cleaned, and the materials used should be eliminated as HAZARDOUS WASTE.
4. In case Irinotecan Aurovitas comes into contact with the skin, rinse the affected area with plenty of running water and then wash with water and soap. In case of contact with mucous membranes, rinse the contact area thoroughly with water. If you feel any discomfort, contact a doctor.
5. In case Irinotecan Aurovitas comes into contact with the eyes, rinse them thoroughly with plenty of water. Contact an ophthalmologist immediately.

Preparation of the Solution for Infusion

Irinotecan Aurovitas concentrate for solution for infusion is designed to be used in intravenous infusion after dilution in the recommended diluents: 0.9% sodium chloride solution or 5% glucose solution. With a graduated syringe, extract the necessary amount of Irinotecan Aurovitas concentrate from the vial, under aseptic conditions, and inject it into a 250 ml infusion bag or bottle. The solution to be infused should be carefully mixed by manual rotation.

If a precipitate is observed in the vials or after dilution, the product should be discarded according to the usual procedures for the elimination of cytotoxic agents.

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 for the preparation, administration, or that come into contact with irinotecan should be eliminated according to local regulations for the handling of cytotoxic compounds.