Irinotecan Tarbis 20 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

irinotecan hydrochloride trihydrate

Read the entire 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, ask your doctor or pharmacist.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

Irinotecan Tarbis is an anticancer medication containing the active substance irinotecan hydrochloride trihydrate.

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

Irinotecan is indicated in combination with other medicines 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 progressed after initial treatment with fluorouracil.

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

Do not use Irinotecan Tarbis

• if you have chronic inflammatory bowel disease and/or intestinal obstruction.
• if you are allergic to irinotecan hydrochloride trihydrate or to any of the other components of this medicine (listed in section 6).
• if you are breastfeeding (see section 2).
• if you have elevated levels of bilirubin in the blood greater than 3 times the upper limit of normal.
• if you have severe bone marrow insufficiency.
• if your general health condition is poor (WHO performance status greater than 2).
• if you are taking or have recently taken St. John’s Wort (a herbal extract containing Hypericum).
• if you are due to receive or have recently received live attenuated vaccines (vaccines against yellow fever, varicella, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, influenza) and during the 6 months following discontinuation 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

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

• if you have Gilbert’s syndrome, a hereditary condition that may cause elevated bilirubin levels and jaundice (yellowing of the skin and eyes).

Take special care with irinotecan. The use of irinotecan should be restricted to specialized units for the administration of cytotoxic chemotherapy, and must only be administered under the supervision of a physician experienced in the use of antineoplastic chemotherapy.

Diarrhea

Irinotecan may cause diarrhea, which in some cases can be severe. This may begin a few hours or a few days after infusion of the medicine. If not treated, it can lead to dehydration and serious electrolyte imbalances, which may be fatal. Your doctor will prescribe a medicine to help prevent or control this adverse effect. Make sure to obtain the medicine immediately so you have it at home when needed.

• Take the medicine as prescribed by your doctor at the first sign of loose or frequent stools.
• Drink large amounts of water and/or electrolyte-containing beverages (mineral water, soda, or soup).
• Contact your doctor or nurse if you still have diarrhea, especially if it lasts more than 24 hours, or if you feel confused, dizzy, or faint.

Neutropenia (reduction in certain white blood cells)

This medicine may decrease white blood cell counts, mainly in the weeks following administration. This may increase the risk of developing an 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 close contact with people who are ill or have infections. Inform your doctor immediately if you develop signs of infection.

Blood monitoring

Your doctor will likely perform blood tests before and during treatment to monitor the effects of the medicine on blood counts or blood chemistry. Depending on the test results, you may require additional medicines to help manage these effects. Your doctor may also reduce or delay your next dose of this medicine, or even discontinue treatment completely. Keep all your scheduled doctor visits and laboratory tests.

This medicine may reduce platelet counts in the weeks following administration, increasing 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 experience 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 medicine or in the first few days afterward. Your doctor may give you medicines before treatment to help prevent nausea and vomiting. Your doctor will likely prescribe anti-nausea medicines for use at home. Keep these medicines on hand for when you need them. Contact your doctor if you are unable to take fluids orally due to nausea and vomiting.

Acute cholinergic syndrome

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

Lung disorders

Rarely, people taking this medicine may develop serious lung problems. Inform your doctor immediately if you develop a cough or worsening cough, difficulty breathing, or fever. Your doctor may need to discontinue your treatment to manage this condition.

This medicine may increase the risk of serious blood clots in the veins of the legs or lungs, which may travel to other parts of the body, such as the lungs or brain. Inform your doctor immediately if you experience chest pain, difficulty breathing, or swelling, pain, redness, or warmth in an arm or leg.

Chronic inflammatory bowel disease 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 have an increased risk of developing bone marrow suppression. Talk to your doctor before starting treatment with irinotecan.

Kidney function

Cases of renal dysfunction have been reported.

Heart disorders

Inform your doctor if you have or have had heart disease or if you previously received cancer medicines. Your doctor will monitor you closely and discuss how risk factors (e.g., smoking, high blood pressure, high fat levels) can be reduced.

Vascular disorders

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

Other

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

For information on contraception and breastfeeding, 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 medicine if you plan to undergo surgery or any medical procedure.

If used in combination with other cancer medicines for your condition, make sure to also read the package leaflet of the other medicines.

If your doctor has told you that you have an intolerance to certain sugars, consult your doctor before taking this medicine.

Other medicines and Irinotecan Tarbis

Irinotecan may interact with several medicines and supplements, which may increase or decrease the level of the medicine in your blood. Inform your doctor or pharmacist if you are using, have recently used, or might 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 herbal 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 blood vessel growth inhibitor),
• cetuximab (an epidermal growth factor receptor (EGFR) inhibitor).

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

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

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

There may be other medicines that interact with irinotecan. Consult your doctor, pharmacist, or nurse about the use of other medicines, herbal products, and supplements, and whether alcohol could cause problems with this medicine.

Contraception, pregnancy, breastfeeding, and fertility

Contraception

If you are a woman of childbearing age, you must use an effective method of contraception during treatment and for at least 6 months after stopping treatment.

As a man, you must use an effective method of contraception during treatment and for at least 3 months after completing treatment. It is important to consult your doctor about which 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 ensure 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 metabolites are excreted in breast milk. You must stop breastfeeding during treatment with this medicine.

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

Fertility

Studies have not been conducted; however, this medicine may affect fertility. Talk to your doctor before taking this medicine about potential risks and possible effects on your reproductive capacity.

Driving and use of machines

In the first 24 hours after administration of irinotecan, you may experience dizziness or visual disturbances. If this occurs, do not drive or operate machinery until these symptoms resolve.

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 disorder, this medicine must not be given. Patients with HFI cannot break down fructose, which may lead to serious adverse effects.

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

This medicine contains 45 mg of sorbitol per mL, equivalent to 90 mg/2 mL, 225 mg/5 mL, 675 mg/15 mL, 1.125 mg/25 mL, and 1.687.5 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 for this medicine as indicated by your doctor. If in doubt, consult your doctor again.

Irinotecan Tarbis will be administered by healthcare professionals.

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

Some people are genetically more likely to experience certain side effects from this medicine.

The amount of irinotecan you will receive depends on many factors, including your height and weight, your general 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 intravenously (IV). You will receive this injection at 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 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 infusion.

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

Currently, there are several recommended treatment regimens 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 a number of factors, including the treatment regimen, your body size, age, overall health, blood counts, liver function, whether you have received radiation to the abdomen/pelvis, and whether you are experiencing side effects such as diarrhea.

Only your doctor can determine the duration of treatment.

If you use more Irinotecan Tarbis than you should

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

If you forget to use Irinotecan Tarbis

Contact your doctor for instructions if you miss an appointment for your irinotecan infusion.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience 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 urgent medical attention if you have any of these signs 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 the healthcare professional immediately. Medications can be given to stop and/or reduce this early adverse effect).
• Late diarrhea: begins more than 24 hours after receiving this medicine. Because of the risks of dehydration and electrolyte imbalance associated with diarrhea, it is important to stay in contact with healthcare professionals for monitoring and to receive recommendations regarding medications and dietary changes.

Tell 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.

Frequency not known (cannot be estimated from available data):

• Severe, persistent, bloody diarrhoea (which may be associated with stomach pain or fever), caused by a bacterium called Clostridium difficile.

• Blood infection.

• Dehydration (due to diarrhoea and vomiting).

• Dizziness, rapid heartbeat, and paleness (a condition called hypovolemia).

• Allergic reaction.

• Transient speech disorders during or shortly after treatment.

• Tingling.

• High blood pressure (during or after infusion).

• Heart problems*.

• Lung disease causing wheezing and difficulty breathing (see section 2).

• Hiccups.

• Intestinal obstruction.

• Enlargement of the colon.

• Intestinal bleeding.

• Inflammation of the large intestine.

• Abnormal laboratory test results.

• Intestinal perforation.

• Fatty liver.

• Skin reactions.

• Reactions at the site of administration.

• Low blood potassium levels.

• Low blood salt levels, mainly related to diarrhoea and vomiting.

• Muscle cramps.

• Kidney problems*.

• Low blood pressure*.

• Fungal infections.

• Viral infections.

• These events have been observed infrequently in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or blood infections.

Reporting of adverse reactions

If you experience any adverse reaction, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es.

By reporting adverse reactions, you can help provide 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 expiry date stated on the carton and container following EXP. The expiry date is the last day of the month indicated. Your doctor will check this.

Storage conditions

No special storage conditions are required.

Shelf life

Before dilution: 2 years

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

6. Contents of the pack and other information

Composition of Irinotecan Tarbis

The active substance 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 injections.

Appearance of the product and contents of the container

Concentrate for solution for infusion.

Pale yellow solution, free from visible particles.

This medicine is supplied in single vials of different sizes: 2 ml, 5 ml, 15 ml, 25 ml, and 37.5 ml.

Only certain pack sizes may be commercially available.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

The Netherlands

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

Germany: Irinotecan Amarox 20 mg/ml concentrate for solution for infusion

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

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

Date of the most recent review of this summary: October 2022

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

………………………………………………………………………………………………..

This information is intended for healthcare professionals only:

Instructions for healthcare personnel on safe handling of Irinotecan Tarbis

As with all cytotoxic agents, irinotecan must be prepared and handled with care. The use of protective goggles, mask, and gloves is mandatory.

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

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

If cloudiness or precipitation is observed in the vial or after dilution of the concentrate, the product must not be used and should be discarded.

Preparation of the infusion solution

As with any injectable drug, the infusion solution of irinotecan must be prepared aseptically.

If a precipitate is observed in the vial or in the infusion solution, discard the product according to standard procedures for cytotoxic agents.

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

Do not mix with other medicines.

Stability after dilution

The diluted irinotecan solution is physically and chemically stable for up to 28 days as an infusion solution (0.9 % w/v sodium chloride solution or 5 % w/v 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 standpoint, immediate use is recommended. If the product is not used immediately after dilution, storage times and conditions are the user's responsibility and normally should not exceed 24 hours between 2 °C and 8 °C, unless the dilution was performed under controlled aseptic conditions.

Warnings regarding visible signs of deterioration

Do not use irinotecan if a precipitate is observed in the vials or in the diluted solution. In such cases, the product must be discarded according to standard procedures for cytotoxic waste disposal. Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

Administration

For information on administration, refer to the summary of product characteristics of Irinotecan Tarbis.

Disposal:

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.