Prospecto: information for the patient

Irinotecán Glenmark 20mg/mL concentrate for infusion solution EFG

irinotecan hydrochloride trihydrate

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

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

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

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

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

Irinotecán is an anticancer medication that contains the active ingredient irinotecan hydrochloride trihydrate.

The irinotecan hydrochloride trihydrateinterferes with the growth and spread of cancer cells in the body

Irinotecanis 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 progressed after initial treatment with fluorouracil.

No use Irinotecán Glenmark

• 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 overall health status is not good (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 to receive or have recently received live attenuated vaccines (vaccines against yellow fever, varicella, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, and influenza) and for 6 months after chemotherapy.

If you are taking 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 (yellowing of the 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 should only be administered under the supervision of a qualified doctor in the use of antineoplastic chemotherapy.

Dysentery

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. Make sure to obtain the medication immediately to have it at home when you need it.

• Takethe medication as told by your doctor with the first sign of loose stools or frequent defecation.
• Drinklarge 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 may decrease the white blood cell count, mainly in the weeks following the administration of the medication. This may 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, cough, or sputum production. Avoid being near people who are sick or have infections. Inform your doctor immediately if you experience signs of infection.

Hematology

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, you may need medications to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medication, or even stop it completely. Keep all your medical 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 experience unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black, tarry stools.

Nausea (feeling of discomfort)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 that you can 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 may affect the part of your nervous system that controls bodily secretions, leading to the so-called acute cholinergic syndrome. Symptoms may include excessive nasal secretion, 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 medications that can help control them.

Respiratory disorders

In rare cases, people taking this medication experience severe lung problems. Inform your doctor immediately if you start with 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 significant 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 experience chest pain, difficulty breathing, or swelling, pain, redness, or heat in an arm or leg.

Chronic inflammatory bowel disease and/or intestinal obstruction

Contact your doctor if you experience 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.

Renal function

Cases of renal dysfunction have been reported.

Cardiovascular disorders

Inform your doctor if you have or have had a heart disease or if you have previously received anticancer 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 disorders

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

Others

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 difficulties. 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 medications.

For information on contraception and breastfeeding, see the information provided later in the section on 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 are taking this medication in combination with other anticancer medications to treat your disease, make sure to also read the prospectus of the other medications.

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

Other medications and Irinotecán Glenmark

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

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

Inform your doctor, pharmacist, or nurse before irinotecan is administered 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 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, dietary supplements, and if alcohol can cause problems with this medication.

Contraception, Pregnancy, Breastfeeding, and Fertility

Contraception

If you are a woman of childbearing age, you should use effective contraceptive methods during and for 6 months after completing treatment.

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

Pregnancy

This medication may 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 metabolite were measured in breast milk.. Breastfeeding should be discontinued during 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.Before using this medication, talk to your doctor about the possible risk with this medication and options to preserve your ability to have children.

Driving and operating machinery

In the first 24 hours or so after administration of this medication, you may experience dizziness or vision disturbances. If you experience these symptoms, do not drive or operate machinery.

This medication contains sorbitol

This medication 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 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, abdominal cramps, or diarrhea.

This medication contains sodium

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

Irinotecán will be administered by healthcare professionals.

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

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

The amount of irinotecán 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.

Irinotecán is injected into a vein by intravenous (IV) route and will be administered in a clinic or hospital. Irinotecán 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 irinotecán. You may need to continue taking these medications for at least one day after irinotecán administration.

Inform your caregivers if you feel burning, pain, or swelling around the needle when irinotecán 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 irinotecán, inform your healthcare professional immediately.

Currently, several treatment regimens are recommended for irinotecán. It is usually administered once every 3 weeks (irinotecán administered alone) or once every 2 weeks (irinotecán administered in combination with 5FU/AF chemotherapy). The dose will depend on various 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 Irinotecán Glenmark 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 ingested.

If you forgot to use Irinotecán Glenmark

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

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, or 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 reactions
• Transient speech disorders during or shortly after treatment
• Tingling
• 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
• Skin 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 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.

For single use only.

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

This medication does not require special storage conditions.

After dilution

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition ofIrinotecan 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 vial of 2 ml contains 40 mg of irinotecan hydrochloride trihydrate.
  • A vial of 5 ml contains 100 mg of irinotecan hydrochloride trihydrate.
  • A vial of 15 ml contains 300 mg of irinotecan hydrochloride trihydrate.
  • A vial of 25 ml 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 contents of the package

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

40 mg/2 ml:

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

100 mg/5 ml:

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

300 mg/15 ml:

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

500 mg/25 ml:

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

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

Only some package sizes may be commercially available.

Marketing authorization holder andresponsible manufacturer

Marketing authorization holder:

Glenmark Arzneimittel GmbH

Industriestr. 31

82194 Gröbenzell

Germany

Responsible manufacturer:

APIS Labor GmbH

Resslstraße 9

9065 Ebenthal in Kärnten

Austria

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

Viso Farmacéutica S.L.U.

c/ Retama 7, 7ª planta

28045 Madrid

Last revision date of this leaflet:February 2023.

This information is intended solely for healthcare professionals:

Instructions for personnel on safe handling of Irinotecan Glenmark

Like other antineoplastic agents, the infusion 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 mucous membranes, wash immediately with water.

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

If 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 infusion solution

Like other infusions, the infusion of irinotecan should be prepared using aseptic techniques.

If precipitation 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.

Aspirate aseptically the required amount of irinotecan concentrate from the vial with a calibrated syringe and inject into a 250 mL infusion bag or bottle containingsodium chloride0.9% or glucose5%. Mix the infusion solution carefully by manual rotation.

Do not mix with other medications.

Shelf life

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

If the dilution is not stored protected from light and moisture, 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 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 infusion solution, the product should be discarded following the usual procedures for the elimination of cytotoxic agents.

Administration

For information about administration, please refer to the Irinotecan Glenmark Technical Data Sheet.

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,applicable to the elimination of cytotoxic agents.