IRINOTECAN GLENMARK 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Patient Information Leaflet

Irinotecan Glenmark 20mg/mL concentrate for solution for infusion EFG

irinotecan hydrochloride trihydrate

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of the pack

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

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

Irinotecan is an anticancer medicine that contains 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 colon or rectal cancer.

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

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

Do not use Irinotecan Glenmark

• if you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6).
• if you have a chronic inflammatory bowel disease or intestinal obstruction.
• if you are breast-feeding (see section 2).
• if your bilirubin level is more than 3 times the upper limit of the normal range.
• if you have severe bone marrow failure.
• if your general health is not good (WHO performance status more than 2).
• if you are taking or have recently taken St. John's Wort (a herbal extract containing Hypericum).
• if you are going to receive or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, flu) and for 6 months after the end of chemotherapy.

If you are taking irinotecan in combination with other medicines, make sure to also read the patient information 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 levels of bilirubin and jaundice (yellowing of the skin and eyes).

Be careful with irinotecan. The use of irinotecan should be restricted to specialized units in the administration of cytotoxic chemotherapy and should only be administered under the supervision of a qualified physician in the use of antineoplastic 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 serious 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 directed by your doctor with 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, cough, or expectoration. Avoid being near people who are sick or have infections. Inform your doctor immediately if you show signs of infection.

Hematology

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 biochemistry. Based on the results of the analysis, you may need medicines to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medicine, or even stop it altogether. Keep all your medical 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 that contain 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 (feeling unwell) and vomiting

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

Acute cholinergic syndrome

This medicine can affect the part of your nervous system that controls body secretions, leading to the so-called cholinergic syndrome. Symptoms can include runny nose, increased salivation, 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.

Respiratory disorders

Rarely, people taking this medicine have serious lung problems. Inform your doctor immediately if you start coughing or your cough worsens, have difficulty breathing, and have a 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 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 disorders

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

Vascular disorders

Irinotecan is rarely associated with circulatory disorders (blood clots that develop in the vessels 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 these symptoms, such as changing the way you eat or brush your teeth. If necessary, your doctor may prescribe pain medicines.

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

Tell 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 anticancer medicines to treat your disease, make sure to also read the patient information leaflet of the other medicines.

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

Other medicines and Irinotecan Glenmark

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

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

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

This medicine can cause severe diarrhea. Try to avoid the use of 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 your other medicines, herbal products, and supplements, and whether alcohol can cause problems with this medicine.

Contraception, pregnancy, breastfeeding, and fertility

Contraception

If you are a woman of childbearing age, you must use effective contraceptive methods during and up to 6 months after the end of treatment.

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

Pregnancy

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

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

Breastfeeding

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

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

Fertility

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

Driving and using machines

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

This medicine contains sorbitol

This medicine contains 45 mg of sorbitol in each mL. 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.

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

This medicine contains sodium

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

3. How to use Irinotecan Glenmark

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

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

Some people are genetically more prone to having some side effects of the medicine.

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

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

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

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

Several treatment schedules 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/FA chemotherapy). The dose will depend on several factors, including the treatment schedule, your body size, age, and general health, your blood counts, liver function, whether you have received radiation to the abdomen or pelvis, and whether you have any side effects, such as diarrhea.

Only your doctor can assess the duration of treatment.

If you use more Irinotecan Glenmark than you shouldSeek emergency medical attention. The symptoms of overdose may include some of the serious side effects listed in this leaflet.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you miss a dose of Irinotecan Glenmark

Consult your doctor for instructions if you miss an appointment for the administration of irinotecan.

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

4. Possible Adverse Effects

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

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

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

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

Unknown frequency (cannot be estimated from available data)

• Severe, persistent, or bloody diarrhea (which may be associated with stomach pain or fever), caused by a bacterium called Clostridium difficile
• Blood infection
• Dehydration (due to diarrhea and vomiting)
• Dizziness, rapid heartbeat, and paleness (a condition called hypovolemia)
• Allergic reactions
• Transient speech disorders during or shortly after treatment
• Numbness
• High blood pressure (during or after perfusion)
• Heart problems*
• Lung disease that causes wheezing and difficulty breathing (see section 2)
• Hiccup
• Intestinal obstruction
• Colon enlargement
• Intestinal bleeding
• Inflammation of the large intestine
• Abnormal laboratory test results
• Intestinal perforation
• Fatty liver
• Skin reactions
• Reactions at the administration site
• Low potassium levels in the blood
• Low salt levels in the blood, mainly related to diarrhea and vomiting
• Muscle cramps
• Kidney problems*
• Low blood pressure*
• Fungal infections
• Viral infections

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Irinotecan Glenmark

Keep this medicine out of sight and reach of children.

For single use.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

After dilution

The product must be used within 24 hours after dilution. The dilution must have been stored between 5°C and 25°C.

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Irinotecan Glenmark

• The active ingredient is irinotecan hydrochloride trihydrate. Each milliliter (ml) of solution contains 20 mg of irinotecan hydrochloride trihydrate equivalent to 17.33 mg of irinotecan.
• • A 2 ml vial contains 40 mg of irinotecan hydrochloride trihydrate.
  • A 5 ml vial contains 100 mg of irinotecan hydrochloride trihydrate.
  • A 15 ml vial contains 300 mg of irinotecan hydrochloride trihydrate.
  • A 25 ml vial contains 500 mg of irinotecan hydrochloride trihydrate.
• The other components are sorbitol (E420), lactic acid (E270), water for injectable preparations, sodium hydroxide (E524), and hydrochloric acid (E507) (for pH adjustment).

Appearance of the Product and Package Contents

Irinotecan Glenmark is a clear, colorless to pale yellow aqueous solution, free of visible particles. pH 3.0 to 3.8.

40 mg/2 ml:

Type I flint glass vial with a rubber stopper (bromobutyl omniflex plus) and sealed with a blue dark aluminum flip-off cap.

100 mg/5 ml:

Type I flint glass vial with a rubber stopper (bromobutyl omniflex plus) and sealed with a light blue aluminum flip-off cap.

300 mg/15 ml:

Type I flint glass vial with a rubber stopper (bromobutyl omniflex plus) and sealed with a dark blue aluminum flip-off cap.

500 mg/25 ml:

Type I flint glass vial with a rubber stopper (bromobutyl omniflex plus) and sealed with a dark blue aluminum flip-off cap.

Package sizes:

40 mg/2 ml: 1 vial, 5 vials, 10 vials

100 mg/5 ml: 1 vial, 5 vials, 10 vials

300 mg/15 ml: 1 vial

500 mg/25 ml: 1 vial

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Glenmark Arzneimittel GmbH

Industriestr. 31

82194 Gröbenzell

Germany

Manufacturer:

APIS Labor GmbH

Resslstraße 9

9065 Ebenthal in Kärnten

Austria

You can request more information about this medicine by contacting the local representative of the Marketing Authorization Holder:

Glenmark Farmacéutica, S.L.U.

C/ Retama 7, 7th floor

28045 Madrid

Spain

Date of the last revision of this prospectus:February 2023.

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 Safe Handling of Irinotecan Glenmark

Like other antineoplastic agents, the perfusion of irinotecan should be prepared and handled with caution. Protective glasses, mask, and gloves should be used.

If irinotecan comes into contact with the skin, wash immediately with plenty of water and soap. If irinotecan comes into contact with the mucous membranes, wash immediately with water.

Like all perfusions, irinotecan should be prepared using aseptic techniques.

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

Preparation for the Solution for Perfusion

Like other perfusions, the perfusion of irinotecan should be prepared using aseptic techniques.

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

Aseptically withdraw the required amount of irinotecan concentrate from the vial with a calibrated syringe and inject into a 250 mL perfusion bag or bottle containing a 0.9% sodium chloride solution or a 5% glucose solution. Mix the solution to be perfused thoroughly by manual rotation.

Do not mix with other medicines.

Validity Period

The chemical and physical stability after dilution of the concentrate has been demonstrated for 28 days (in a 0.9% sodium chloride solution and a 5% glucose solution) stored in LDPE or PVC containers between 5°C and 30°C, protected from light and humidity.

If the dilution is not stored protected from light and humidity, the chemical and physical stability has been demonstrated for up to 3 days.

From a microbiological point of view, the product should be used immediately. If not, the storage times and conditions prior to use will be the responsibility of the user and should not normally exceed 24 hours at 25°C, unless the dilution has been performed in validated and controlled aseptic conditions.

Warning about Visual Signs of Deterioration

If visible particles are observed in the concentrate or in the solution for perfusion, the product should be eliminated following the procedures for the elimination of cytotoxic agents.

Administration

For information regarding administration, read the Summary of Product Characteristics of Irinotecan Glenmark.

Elimination

The elimination of unused medicine and all materials that have come into contact with it will be carried out according to local regulations applicable to the elimination of cytotoxic agents.