IRINOTECAN TARBIS 20 mg/mL concentrate for infusion solution

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

Do not use Irinotecan Tarbis

• if you have a chronic inflammatory bowel disease and/or intestinal obstruction.
• if you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding (see section 2).
• if you have a bilirubin level in your blood more than 3 times the upper normal limit.
• if you have severe bone marrow failure.
• if your general state of health is poor (WHO performance status more than 2).
• if you are taking or have recently taken St. John's Wort (a plant-based extract containing Hypericum).
• if you need to receive or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, flu) and for 6 months after stopping chemotherapy.

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

Warnings and precautions

Talk to your doctor, pharmacist or nurse before starting treatment with irinotecan.

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

Be careful with irinotecan. 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 doctor specialized in the use of anti-neoplastic 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 the 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 get the medicine immediately to have it at home when you need it.

• Take the medicine as prescribed by your doctor at the first sign of loose or frequent stools.
• Drink plenty of water and/or electrolyte-rich beverages (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 the 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 more), 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

It is likely that your doctor will perform blood tests before and during treatment to monitor the effects of the medicine on your blood count or blood chemistry. Depending on the results of the analysis, you may need medicines to help treat the effects. Your doctor may also 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 the administration, which can increase the risk of bleeding. Talk to your doctor before taking any medicine or supplement that can affect your 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.

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. Your doctor will likely prescribe anti-nausea medicines for you 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

In rare cases, 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 closely monitor you and discuss how to reduce risk factors (such as smoking, high blood pressure, and high fat content).

Vascular disorders

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

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 the way you eat or brush your teeth. If necessary, your doctor may prescribe pain medicines.

For information on contraception and breast-feeding, see the information provided below in the Contraception, pregnancy, breast-feeding, and fertility section.

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, talk to your doctor before taking this medicine.

Other medicines and Irinotecan Tarbis

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, have recently used, or may need to use any of the following:

• 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 the immune system to prevent transplant rejection (cyclosporine and tacrolimus),
• medicines used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamide),
• vitamin K antagonists (an anticoagulant used to thin the blood, 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 irinotecan is administered to you 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 medicine without talking to 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. Talk to your doctor, pharmacist, or nurse about the use of other medicines, plant-based products, and supplements, and whether alcohol can cause problems with this medicine.

Contraception, pregnancy, breast-feeding, 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 stopping treatment.

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

Pregnancy

This medicine can 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, talk to your doctor or pharmacist before using this medicine.

Breast-feeding

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

If you are breast-feeding, talk to your doctor or pharmacist before using this medicine.

Fertility

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

Driving and using machines

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

Irinotecan Tarbis contains sorbitol

This medicine 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 must not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Talk to 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 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, 1.125 mg/25 mL, and 1.6875 mg/37.5 mL.

Irinotecan Tarbis contains sodium

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

3. How to use Irinotecan Tarbis

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

Irinotecan Tarbis will be administered to you by healthcare professionals.

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

Some people are genetically more prone to having certain side effects with this medicine.

The amount of irinotecan you receive will depend on many factors, including your height and weight, your overall health, or other health problems, and the type of cancer or disease being treated. 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 IV 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 infusion.

Inform your caregivers if you feel burning, pain, or swelling around the needle when irinotecan is administered. 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.

There are currently several recommended treatment schedules for irinotecan. It is usually administered once every 3 weeks (irinotecan alone) or once every 2 weeks (irinotecan in combination with 5FU/FA chemotherapy). The dose will depend on a number of factors, including the treatment program, your body size, age, and overall health, your blood counts, how well your liver is working, whether you have received radiation to the abdomen/pelvis, and whether you have side effects such as diarrhea.

Only your doctor can assess the duration of treatment.

If you use more Irinotecan Tarbis than you should

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

If you miss a dose of Irinotecan Tarbis

Talk to your doctor for instructions if you miss a scheduled infusion of irinotecan.

If you have any other questions about 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 reduce 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 changes.

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 reaction.
• 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 site of administration of the medicine.
• 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, 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: https://www.notificaram.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Irinotecan Tarbis

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

Do not use this medicine after the expiration date that appears on the box and on the container after CAD. The expiration date is the last day of the month indicated. Your doctor will check it.

Storage Conditions

No special storage conditions are required.

Duration

Before dilution: 2 years

After dilution: The medicine will be administered to you within 24 hours after dilution. The diluted solution may have been stored between 2 °C and 8 °C in the refrigerator.

6. Package Contents and Additional Information

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

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

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

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

A 37.5 ml vial 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 injectable preparations.

Appearance of the Product and Package Contents

Concentrate for solution for infusion.

Pale yellow 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 package sizes may be marketed.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

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 Konzentrat zur Herstellung einer Infusionslösung

Spain: Irinotecan Tarbis 20mg/ml concentrate for solution for infusion EFG

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

Date of the last revision of this prospectus: October 2022

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 personnel on the safe handling of Irinotecan Tarbis

Like 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.

As with all injectable medicines, irinotecan must be prepared under aseptic conditions.

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

Preparation of the Infusion Solution

Like any other injectable drug, 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 agents.

Aseptically extract the calculated amount of irinotecan concentrate for solution for infusion from the vial to a syringe and transfer it to an infusion bag or bottle containing a 0.9% (w/v) sodium chloride solution or a 5% (w/v) glucose infusion solution. Mix the infusion solution well in the bag or bottle by manual rotation.

Do not mix with other medicines.

Duration

The diluted solution of irinotecan is physically and chemically stable for up to 28 days as an infusion solution (0.9% sodium chloride solution and 5% glucose solution) when stored in PVC containers at 5 °C protected from light.

When the diluted solution is not stored and protected from light, it is physically and chemically stable for up to 3 days.

From a microbiological point of view, immediate use is recommended. If the product is not used immediately after dilution, the storage times and conditions are the responsibility of the user and normally do not exceed 24 hours between 2 °C and 8 °C, unless the dilution has been performed under controlled aseptic conditions.

Warnings against some visible signs of deterioration

Do not use irinotecan if you observe a precipitate in the vials or in the diluted solution. In this case, the product must be discarded according to standard procedures for the disposal of cytotoxic waste. Do not throw any medicine into the sewage system. Ask your pharmacist how to dispose of unused medicines. 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 medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.