Leaflet: information for the user

Irinotecán Tarbis 20mg/ml concentrate for infusion solution 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 or pharmacist.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

1. What is Irinotecán Tarbis and what it is used for

2. What you need to know before starting to use Irinotecán Tarbis

3. How to use Irinotecán Tarbis

4. Possible side effects

5. Storage of Irinotecán Tarbis

6. Contents of the pack and additional information

Irinotecán Tarbis is a cancer medication that contains irinotecan hydrochloride trihydrate as its active ingredient.

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

Irinotecan is indicated in combination with other medications for the treatment of patients with advanced or metastatic colorectal cancer.

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

No use Irinotecán Tarbis

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

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

Warnings and Precautions

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

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

Be especially careful with irinotecan. 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 doctor in the use of antineoplastic chemotherapy.

Diarrea

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

• Take the medication as prescribed by your doctor at the first sign of loose stools or frequent bowel movements.
• Drink large amounts of water and/or electrolyte-rich beverages (water with gas, soda, or soup).
• Call your doctor or nurse if you still have diarrhea, especially if it lasts more than 24 hours, or if you feel dizzy, nauseous, or faint.

Neutropenia (decrease in some white blood cells)

This medication can decrease the white blood cell count, mainly in the weeks following the administration of the medication. 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, painful urination, new cough, or sputum.

Blood tests

Your doctor may perform blood tests before and during treatment to monitor the effects of the medication on the blood count or blood chemistry. According to the test results, your doctor may need to prescribe medications to help treat the side effects. Your doctor may also reduce or delay your next dose of this medication, or even discontinue it altogether. Make sure to keep all your doctor's appointments and laboratory tests.

This medication can decrease the platelet count in the weeks following administration, which can increase the risk of bleeding. Talk to your doctor before taking any medications or supplements that may affect your body's ability to stop bleeding, such as aspirin or medications containing aspirin, warfarin, or vitamin E. Inform your doctor immediately if you have unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black, tarry stools.

Nausea and vomiting

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

Acute cholinergic syndrome

This medication can affect the part of your nervous system that controls bodily secretions, leading to the so-called acute cholinergic syndrome. Symptoms may include nasal secretion, increased saliva, excessive tearing in the eyes, sweating, flushing, abdominal cramps, and diarrhea. Inform your doctor or nurse immediately if you notice any of these symptoms, as there are medications that can help control them.

Pulmonary problems

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 discontinue your treatment to treat this problem.

This medication can increase the risk of large 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 heat in an arm or leg.

Chronic inflammatory intestinal disease and/or intestinal obstruction

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

Radiation therapy

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

Kidney function

There have been reports of kidney dysfunction.

Cardiac problems

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

Vascular problems

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

Other

This medication can cause mouth ulcers or lip ulcers, often in the first few weeks after starting treatment. This can cause mouth pain, bleeding, or even eating difficulties. Your doctor or nurse may suggest ways to reduce this, such as changing the way you eat or brush your teeth. If necessary, your doctor may prescribe medications for pain.

For information on contraception, pregnancy, breastfeeding, and fertility, see the information provided below 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 type of procedure.

If you use it in combination with other cancer medications for your disease, make sure to also read the prospectus of the other medications.

If your doctor has told you that you have intolerance to some sugars, consult your doctor before taking this medication.

Other medications and Irinotecán Tarbis

Irinotecan can interact with several medications and supplements, which can increase or decrease the level of the medication in your blood.Inform your doctor, pharmacist, or nurse before you are administered irinotecan if you are already taking, have recently taken, or may need to take any of the following:

• Medications used to treat epilepsy (carbamazepine, phenobarbital, phenytoin, and fosphenytoin),
• Medications used to treat fungal infections (ketoconazole, itraconazole, voriconazole, and posaconazole),
• Medications used to treat bacterial infections (clarithromycin, erythromycin, and telithromycin),
• Medications used to treat tuberculosis (rifampicin and rifabutin),
• St. John's Wort (a dietary supplement based on plants),
• Live attenuated vaccines,
• Medications used to treat HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others),
• Medications to reduce the immune system to prevent rejection in transplants (ciclosporin and tacrolimus),
• Medications used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamide),
• Antagonists of vitamin K (an anticoagulant used to thin the blood, 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 (EGF)).

Inform your doctor, pharmacist, or nurse before you are administered 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 medication without consulting your doctor first.

This medication can 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 with your doctor, pharmacist, or nurse about the use of other medications, dietary supplements, and products, and if alcohol can cause problems with this medication.

Contraception, pregnancy, breastfeeding, and fertility

Contraception

If you are a fertile woman, you should use an effective contraceptive method during and for 6 months after treatment is discontinued.

As a man, you should use an effective contraceptive method during and for 3 months after treatment is completed. It is essential to consult your doctor about the types of contraceptives that can be used with this medication.

Pregnancy

This medication can cause problems for the fetus if used during conception or during pregnancy. Before starting treatment, your doctor will ensure that you are not pregnant.

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

Breastfeeding

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

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

Fertility

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

Driving and operating machines

In the first 24 hours after administration of irinotecan, you may feel dizzy or have vision disturbances. If this happens, do not drive or operate machinery until it resolves.

Irinotecán Tarbis contains sorbitol

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

This medication contains 45 mg of sorbitol in each mL, which is equivalent to 90 mg/2 mL, 225 mg/5 mL, 675 mg/15 mL, 1.125 mg/25 mL, and 1.6875 mg/37.5 mL.

Irinotecán Tarbis contains sodium

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

Irinotecán Tarbiswill be administered by healthcare professionals.

Your doctor may recommend a DNA test before your first dose ofirinotecán.

Some people are genetically more prone to certain side effects of this medication.

The amount ofirinotecányou 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 being treated. Your doctor will determine your dose and treatment schedule.

Irinotecánis injected into a vein via intravenous (IV) administration. You will receive this injection in a clinic or hospital.Irinotecánmust be administered slowly, and the IV infusion may take up to 90 minutes to complete.

You may be given other medications to prevent nausea, vomiting, diarrhea, and other side effects while receiving irinotecán. You may need to continue taking these medications for at least one day after your irinotecán infusion.

Inform your caregivers if you feel burning, pain, or swelling around the needle when irinotecán is administered. If the medication leaks from the vein, it may cause tissue damage. If you experience pain or notice redness or swelling at the injection site while receiving irinotecán, immediately inform the healthcare professional.

Currently, there are several recommended treatment regimens foririnotecán. It is usually administered once every 3 weeks (irinotecánis administered alone) or once every 2 weeks (irinotecánis administered in combination with 5FU/FA chemotherapy). The dose will depend on a series of factors, including the treatment program, your body size, age, and overall health status, your blood counts, how well your liver is functioning, if you have received radiation in the abdomen/pelvis, and if you have side effects such as diarrhea.

Only your doctor can assess the duration of treatment.

If you use more Irinotecán Tarbis than you should

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

If you forgot to use Irinotecán Tarbis

Consult with your doctor for instructions if you miss a scheduled infusion appointment for irinotecán.

If you have any other questions about using this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

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

• Diarrhea (see section 2).
• Early diarrhea: starts within 24 hours after receiving this medicine, and is accompanied by symptoms such as: runny nose, increased salivation, tearing of the eyes, sweating, flushing, abdominal cramps (this may occur while the medicine is being administered. In this case, inform your healthcare professional immediately. Medications may be administered to stop and/or reduce this early side effect).
• Late diarrhea: starts more than 24 hours after receiving this medicine. Due to dehydration and electrolyte imbalance with diarrhea, it is essential to be in contact with healthcare professionals for control and to obtain recommendations on medications and dietary changes.

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, and bloody diarrhea (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 heartbeat, and paleness (a condition called hypovolemia).
• Allergic reaction.
• Transient speech disorders during or shortly after treatment.
• Tickling.
• Elevated blood pressure (during or after infusion).
• Cardiac problems*.
• Lung disease that produces wheezing and difficulty breathing (see section 2)
• Hypophagia.
• Intestinal obstruction.
• Colon enlargement.
• Intestinal bleeding.
• Colitis.
• Abnormal laboratory test results.
• Intestinal perforation.
• Fatty liver.
• Dermatological reactions.
• Reactions at the injection site.
• Low potassium levels in the blood.
• Low electrolyte levels in the blood, mainly related to diarrhea and vomiting.
• Muscle cramps.
• Renal problems*.
• Low blood pressure*.
• Fungal infections.
• Viral infections.

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

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://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 use this medication after the expiration date that appears on the box and on the packaging after CAD. The expiration date is the last day of the month indicated. Your doctor will verify it.

Storage Conditions

No special storage conditions are required.

Duration

Before dilution:2 years

After dilution:You will be administered the medication within 24 hours after dilution. The diluted solution can be stored between 2 °C and 8 °C in a refrigerator

Composition of Irinotecan Tarbis

The active ingredient is irinotecan hydrochloride trihydrate.

The concentrate contains 20 mg/ml of irinotecan hydrochloride trihydrate (equivalent to 17.33 mg/ml of irinotecan).

A vial of 2 ml contains 34.66 mg of irinotecan as 40 mg of irinotecan hydrochloride trihydrate (40 mg/2 ml).

A vial of 5 ml contains 86.65 mg of irinotecan as 100 mg of irinotecan hydrochloride trihydrate (100 mg/5 ml).

A vial of 15 ml contains 259.95 mg of irinotecan as 300 mg of irinotecan hydrochloride trihydrate (300 mg/15 ml).

A vial of 25 ml contains 433.25 mg of irinotecan as 500 mg of irinotecan hydrochloride trihydrate (500 mg/25 ml).

A vial of 37.5 ml contains 649.87 mg of irinotecan as 750 mg of irinotecan hydrochloride trihydrate (750 mg/37.5 ml).

The other components (excipients) are:

Sorbitol, lactic acid, sodium hydroxide, hydrochloric acid, and water for injection preparations.

Appearance of the product and contents of the package

Concentrate for solution for infusion.

Yellowish pale solution free of visible particles.

This medicine is presented in a single vial with different vial sizes of 2 ml, 5 ml, 15 ml, 25 ml, and 37.5 ml.

Only some sizes of packaging may be commercially available.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Responsible for manufacturing

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

Netherlands

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

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

Spain:Irinotecan Tarbis 20mg/ml concentrate for solution for infusionEFG

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

Last review date of this leaflet: October 2022

Detailed information about this medicine 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:

Instructions for personnel on the safe handling ofIrinotecan Tarbis

As with all antineoplastic substances, irinotecan must be prepared and handled with care. The use of protective glasses, mask, and gloves is mandatory.

If irinotecan comes into contact with your skin, wash it immediately and thoroughly with water and soap. If irinotecan comes into contact with your mucous membranes, wash them immediately and thoroughly with water.

Like all injectable medications, irinotecan must be prepared in aseptic conditions.

If you observe turbidity or condensation in the vial or after dilution of the concentrate, the medication cannot be used and must be discarded.

Preparation of the infusion solution

Like any other injectable medication, the infusion solution of irinotecan must be prepared aseptically.

If you observe any precipitate in the vial or infusion solution, discard the product according to standard procedures for cytotoxic waste. Do not dispose of any medication in wastewater. Ask your pharmacist how to dispose of unused medications. These measures will help protect the environment.

Administration

For information on administration, read the technical data sheet of Irinotecan Tarbis

Elimination:

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.