Prospect: Information for the user

Irinotecan Aurovitas20 mg/ml concentrate for infusion solution

Irinotecan hydrochloride trihydrate

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist, or nurse.

-This medicine has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1.What isIrinotecan Aurovitasand how it is used

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

3.How to useIrinotecan Aurovitas

4.Possible adverse effects

5.Storage ofIrinotecan Aurovitas

6.Contents of the package and additional information

Irinotecán Aurovitas is a cancer medication that contains the active ingredient 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 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 treatment with fluorouracil.

No use Irinotecán Aurovitas

-If you are allergic to irinotecan hydrochloride trihydrate or any of the other components of this medication (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 greater than 3 times the upper limit of the normal range.

-If you have severe bone marrow failure.

-If your general health status is poor (WHO performance status greater than 2).

-If you are taking or have taken recently St. John's Wort (an extract-based plant product containing Hypericum).

-If you are to receive or have received recently live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, flu) and during the 6 months following the interruption of chemotherapy.

If you receive irinotecan in combination with other medications, ensure that you also read the prospectus of the other medications regarding additional contraindications.

Advertencias y precauciones

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

Be especially careful with irinotecan. The use of irinotecan should be limited to specialized units in 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 may lead to dehydration and severe chemical imbalances, which can be fatal. Your doctor will prescribe a medication to help prevent or control this adverse effect. Ensure that you 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 or frequent bowel movements.

-Drink a lot of water and/or drinks with salts (carbonated 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, 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. Ensure that you inform your doctor or nurse immediately if you have any signs of infection, such as fever (38°C or more), chills, pain while urinating, new cough or sputum. Avoid being near people who are sick or have infections. Inform your doctor immediately if you present signs of infection.

Control sanguíneo

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, it may be necessary to take medications to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medication, or even interrupt 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 while brushing your teeth or black and tar-like stools.

Náuseas y vómitos

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, before your treatment, medications 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.

Síndrome colinérgico agudo

This medication may affect the part of your nervous system that controls bodily secretions, leading to the so-called cholinergic syndrome. Symptoms may include nasal secretion, increased saliva, excessive tears in the eyes, sweating, redness, 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.

Trastornos en el pulmón

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.

Inflamación intestinal crónica y/u obstrucción intestinal

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

Radioterapia

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.

Función del riñón

Cases of renal dysfunction have been reported.

Trastornos cardiacos

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 (for example, smoking, high blood pressure and high fat content).

Trastornos vasculares

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

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

Otros

This medication may cause mouth ulcers or lip ulcers, often in the first 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 use it in combination with other cancer medications for your disease, ensure that you 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.

Otros medicamentos e Irinotecán Aurovitas

Inform your doctor or pharmacist if you are using, have used recently or may have to use any other medication, including medications obtained without a prescription.

Irinotecan 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 using or have used any of the following medications:

-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/folinic acid.

-Bevacizumab (an inhibitor of blood vessel growth).

-Cetuximab (an inhibitor of the epidermal growth factor receptor).

Inform your doctor, pharmacist or nurse before they administer irinotecan if you are already receiving or have received recently 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 more medications that interact with irinotecan. Consult your doctor, pharmacist or nurse about your other medications, plant-based products and supplements, and if alcohol can cause problems with this medication.

Anticoncepción, embarazo, lactancia y fertilidad

Anticoncepción

If you are a fertile woman, 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.

Embarazo

This medication may cause problems for the fetus if used 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 intend to become pregnant, consult your doctor or pharmacist before using this medication.

Lactancia

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.

Fertilidad

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 the options that may preserve your ability to have children.

Conducción y uso de máquinas

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

Irinotecán Aurovitas contains sorbitol

This medication contains 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 adverse effects.

Consult your doctor before receiving this medication 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.

Irinotecán Aurovitas contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose; that is, it 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 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 medication.

The amount of irinotecan 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.

Irinotecan is injected into a vein by intravenous (IV) route. 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 medications to prevent nausea, vomiting, diarrhea, and other side effects while receiving irinotecan. You may need to continue taking these medications 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 medication leaks out of the vein, it may cause tissue damage. If you feel pain or notice redness or swelling at the injection site while receiving irinotecan, inform your healthcare professional immediately.

Several treatment regimens are currently recommended for irinotecan. It is usually administered once every 3 weeks (irinotecan administered alone) or once every 2 weeks (irinotecan administered in combination with 5FU/AF chemotherapy). 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 Irinotecan Aurovitas 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 Irinotecan Aurovitas

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

Do not use a double dose to compensate for missed doses.

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: begins 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 may be administered to stop and/or reduce this early side effect).

-Late diarrhea: begins 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 dietary 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 stomach pain or fever), produced by a bacteria called Clostridium difficile.

-Blood infection.

-Dehydration (due to diarrhea and vomiting).

-Dizziness, rapid heart rate, and paleness (a condition called hypovolemia).

-Allergic reactions.

-Transient speech disorders during or shortly after treatment.

-Tickling.

-High blood pressure (during or after infusion).

-Cardiac problems*.

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

-Osteoporosis.

-Intestinal obstruction.

-Colon enlargement.

-Intestinal bleeding.

-Colitis.

-Abnormal results in laboratory tests.

-Intestinal perforation.

-Fatty liver.

-Dermatological reactions.

-Reactions at the site of administration.

-Low potassium levels in the blood.

-Low levels of salts 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 or pharmacist, 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 medication out of the 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 medication after the expiration date that appears on the carton, after CAD. The expiration date is the last day of the month indicated.

The product must be diluted and used immediately after opening.

If prepared in aseptic conditions, the diluted solution can be stored for 24 hours at a temperature below30°Cand for 48 hours between 2-8°C(i.e., in a refrigerator).

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 Aurovitas

-The active ingredient is trihydrate irinotecan hydrochloride.

-1 ml of concentrate contains 20 mg of trihydrate irinotecan hydrochloride, equivalent to 17.33 mg of irinotecan.

-A vial of 2 ml contains 40 mg of trihydrate irinotecan hydrochloride.

-A vial of 5 ml contains 100 mg of trihydrate irinotecan hydrochloride.

-A vial of 15 ml contains 300 mg of trihydrate irinotecan hydrochloride.

-A vial of 25 ml contains 500 mg of trihydrate irinotecan hydrochloride.

-The other components are: sorbitol E420, lactic acid, sodium hydroxide, hydrochloric acid, and water for injectable preparations..

Appearance of the product and contents of the package

Irinotecan Aurovitas 20 mg/ml concentrate for solution for infusion is a transparent, 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

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer responsible

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

O

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

For more information about this medication, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Germany:Irinotecan Aurobindo 20 mg/ml concentrate for the preparation of an infusion solution

Belgium:Irinotecan AB 20 mg/ml concentrate for solution for infusion

Spain:Irinotecan Aurovitas 20 mg/ml concentrate for solution for perfusion

France:IRINOTECAN ARROW 20 mg/ml, solution to be diluted for perfusion

Italy:Irinotican Aurobindo

Netherlands:Irinotecan Aurobindo 20 mg/ml, concentrate for solution for infusion

Portugal:Irinotecano Aurovitas

Last review date of this leaflet: April 2022

Other sources of information

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (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 in aseptic conditions, by experienced personnel, in a designated area. Precautions should be taken to avoid contact with the skin and mucous membranes.

Instructions for safety when preparing irinotecan solution for infusion:

1.A protective hood, as well as protective gloves and a protective 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 bags, and cannulas, syringes, catheters, and tubes used, and cytostatic waste; should be considered hazardous waste and disposed of in accordance with local regulations for the handling of HAZARDOUS WASTE.

3.In case of spill, follow these instructions:

-Wear protective clothing.

-Broken glass should be collected and disposed of in a HAZARDOUS WASTE container.

-Contaminated surfaces should be thoroughly washed with plenty of cold water.

-Cleaned surfaces should be carefully cleaned and materials used should be disposed of as HAZARDOUS WASTE.

4.In case of skin contact with Irinotecan Aurovitas, wash the affected area with plenty of running water and then wash with soap and water. If you experience any discomfort, contact a doctor.

5.In case of eye contact with Irinotecan Aurovitas, wash the eyes thoroughly with plenty of water. Immediately contact an ophthalmologist.

Preparation of the infusion solution

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

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

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

Elimination

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