Irinotecan Glenmark 20 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Irinotecan Glenmark 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, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• 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 Glenmark is and what it is used for
2. What you need to know before using Irinotecan Glenmark
3. How to use Irinotecan Glenmark
4. Possible side effects
5. How to store Irinotecan Glenmark
6. Contents of the pack and other information

1. What Irinotecan Glenmark is and what it is 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 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 Glenmark

Do not use Irinotecan Glenmark

• if you are allergic to irinotecan hydrochloride trihydrate or to any of the other ingredients of this medicine (listed in section 6).
• if you have chronic inflammatory bowel disease or intestinal obstruction.
• if you are breastfeeding (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 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 receiving or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, influenza) and during the 6 months following discontinuation of chemotherapy.

If you are taking 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 experienced in the administration of cytotoxic chemotherapy and must be administered only under the supervision of a qualified 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 couple of days after infusion of the medicine. If left untreated, it may lead to dehydration and serious chemical imbalances, which can be life-threatening. Your doctor will prescribe a medicine to help prevent or control this side effect. Make sure to obtain the medicine immediately so you have it at home when needed.

• Take the medicine exactly as instructed by your doctor at the first sign of loose or frequent bowel movements.
• Drink plenty of water and/or electrolyte-containing fluids (such as mineral water, soda, or soup).
• Contact your doctor or nurse if you still have diarrhea, especially if it lasts longer than 24 hours, or if you feel confused, dizzy, or faint.

Neutropenia (decrease in certain white blood cells)

This medicine may reduce white blood cell counts, especially in the weeks following administration. This may increase the risk of developing infections. Inform your doctor or nurse immediately if you show any signs of infection, such as fever (38°C or higher), chills, pain when urinating, cough, or sputum. Avoid close contact with people who are ill or have infections. Inform your doctor immediately if you develop signs of infection.

Hematology

Your doctor will likely perform blood tests before and during treatment to monitor the medicine’s effects on blood counts or blood biochemistry. Depending on test results, you may need additional medicines to help manage these effects. Your doctor may also need to reduce or delay your next dose, or even discontinue treatment completely. Attend all scheduled medical appointments 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 aspirin or aspirin-containing products, warfarin, or vitamin E. Inform your doctor immediately if you experience unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing 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. You may also be prescribed anti-nausea medicines to take at home. Keep these medicines available 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 what is known as acute cholinergic syndrome. Symptoms may include runny nose, increased salivation, excessive tearing, sweating, flushing, abdominal cramps, and diarrhea. Inform your doctor or nurse immediately if you experience any of these symptoms, as medicines are available to help control them.

Respiratory disorders

Rarely, people taking this medicine may develop serious lung problems. Inform your doctor immediately if you develop a new cough or worsening cough, difficulty breathing, or fever. Your doctor may need to stop 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 one arm or leg.

Chronic inflammatory bowel disease and/or intestinal obstruction

Contact your doctor if you have abdominal pain and constipation, especially if accompanied by bloating and loss of appetite.

Radiotherapy

If you have recently received pelvic or abdominal radiotherapy, you may have an increased risk of developing bone marrow suppression. Talk to your doctor before starting treatment with irinotecan.

Kidney function

Cases of kidney dysfunction have been reported.

Cardiac disorders

Inform 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 risk factors (e.g., smoking, high blood pressure, high fat levels) can be reduced.

Vascular disorders

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

Other

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

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

Inform your doctor or dentist that you are being treated with this medicine if you are planning to undergo surgery or any medical procedure.

If used in combination with other anticancer drugs to treat 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, contact your doctor before using this medicine.

Other medicines and Irinotecan Glenmark

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 for the treatment of epilepsy (carbamazepine, phenobarbital, phenytoin, and fosphenytoin)
• Medicines for the treatment of fungal infections (ketoconazole, itraconazole, voriconazole, and posaconazole)
• Medicines for treating bacterial infections (clarithromycin, erythromycin, and telithromycin)
• Medicines for the treatment of tuberculosis (rifampicin and rifabutin)
• St. John’s wort (a herbal dietary supplement)
• Live attenuated vaccines
• Medicines for treating HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• Medicines to suppress your immune system to prevent transplant rejection (cyclosporine and tacrolimus)
• Medicines for treating 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 (a vascular endothelial growth factor inhibitor, VEGF)
• Cetuximab (an epidermal growth factor receptor inhibitor, EGFR)

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

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 taking this medicine.

There may be other medicines that interact with irinotecan. Consult your doctor, pharmacist, or nurse about your 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 effective contraceptive methods during treatment and for at least 6 months after treatment ends.

If you are a man, you must use an effective contraceptive method during treatment and for at least 3 months after treatment ends. It is important to consult your doctor about which types of contraception can be used with this medicine.

Pregnancy

This medicine may harm the unborn baby 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 metabolite have been detected in human breast milk. Breastfeeding must be discontinued during treatment with this medicine.

If you are breastfeeding, 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 potential risks and options that may preserve your ability to have children.

Driving and using machines

For approximately the first 24 hours after receiving this medicine, you may experience dizziness or visual disturbances. If you experience these symptoms, do not drive or operate machinery.

This medicine contains sorbitol

This medicine contains 45 mg of sorbitol per mL. 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 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, which is essentially “sodium-free.”

3. How to use Irinotecan Glenmark

General recommendations
Irinotecan Glenmark must only be administered under the supervision of a doctor experienced in the use of cancer chemotherapy agents.
Your doctor will determine the dose and duration of treatment with Irinotecan Glenmark based on your body surface area (calculated from your height and weight), your blood counts, and the type and severity of your cancer.
Irinotecan Glenmark is administered by intravenous infusion (slow injection into a vein). The duration of the infusion may vary depending on the treatment regimen prescribed by your doctor.
Your doctor will prescribe additional medications to prevent severe allergic reactions and nausea and vomiting associated with Irinotecan Glenmark.
During and after administration of Irinotecan Glenmark, your doctor will monitor you for signs of allergic reactions.
Your doctor will perform blood tests before each treatment cycle to monitor your blood counts.
Your doctor may adjust the dose of Irinotecan Glenmark or discontinue treatment based on your response and any side effects you experience.

If you receive more Irinotecan Glenmark than you should
Due to the method of administration (in a hospital setting by healthcare professionals), it is unlikely that you will receive more Irinotecan Glenmark than prescribed. However, if this occurs, your doctor will closely monitor you for side effects and provide appropriate treatment as needed.

If you miss a dose of Irinotecan Glenmark
Since Irinotecan Glenmark is administered in a hospital or clinical setting by healthcare professionals, it is unlikely that you will miss a dose. Your treatment schedule will be carefully managed by your doctor.

If you stop using Irinotecan Glenmark
Irinotecan Glenmark treatment is typically given in cycles. Do not stop receiving Irinotecan Glenmark unless instructed by your doctor. Stopping treatment prematurely may reduce its effectiveness.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

Follow exactly the administration instructions for this medicine as indicated by your doctor. If in doubt, consult your doctor again. Irinotecan will be administered by healthcare professionals.

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

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

The amount of irinotecan you will receive depends on many factors, including your height and weight, your general health, 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 intravenously (IV) and will be administered at a clinic or hospital. Irinotecan must be given 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 receiving irinotecan. You may need to continue taking these medicines for at least one day after receiving irinotecan.

Inform 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 may cause tissue damage. If you feel pain or notice redness or swelling at the injection site while receiving irinotecan, inform the healthcare professional immediately.

Several treatment schedules are currently recommended for irinotecan. It is generally administered once every 3 weeks (irinotecan given alone) or once every 2 weeks (irinotecan given in combination with 5FU/AF 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 are experiencing any side effects, such as diarrhea.

Only your doctor can assess the duration of treatment.

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

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to use Irinotecan Glenmark
Consult your doctor for instructions if you miss an appointment for irinotecan administration.

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 may 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, and abdominal cramps (this may occur while the medicine is being administered. In such case, notify the healthcare professional immediately. Medicines may be given to stop and/or reduce this early adverse effect).
  • Late diarrhea: begins more than 24 hours after receiving this medicine. Because 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 modifications.

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

Symptoms	Frequency* of occurrence in monotherapy	Frequency† of occurrence in combination therapy
Abnormally low white blood cell count, which may increase the risk of infection	Very common	Very common
Low red blood cell count, causing fatigue and difficulty breathing	Very common	Very common
Decreased appetite	Very common	Very common
Cholinergic syndrome (see Warnings and precautions)	Very common	Very common
Vomiting	Very common	Very common
Nausea	Very common	Very common
Abdominal pain	Very common	Common
Loss of hair (reversible)	Very common	Very common
Inflammation of mucous membranes	Very common	Very common
Fever	Very common	Common
Feeling of weakness and lack of energy	Very common	Very common
Low platelet count (blood cells that help with clotting), which may lead to bruising or bleeding	Common	Very common
Abnormal liver function test results	Common	Very common
Infection	Common	Very common
Low white blood cell count with fever	Common	Very common
Constipation	Common	Common
Abnormal kidney function test results	Common	Not reported

• 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 the available data)

• Severe, persistent or 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 reactions

• 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 results in laboratory tests

• Intestinal perforation

• Fatty liver

• Skin reactions

• Reactions at the site where the medicine is administered

• Low potassium levels in the blood

• Low levels of salts in the blood, mainly related to diarrhoea 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 diarrhoea and/or vomiting, or blood infections.

Reporting of adverse reactions

If you experience any type of adverse reaction, talk to your doctor or pharmacist, 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 Medicinal Products: www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Irinotecan Glenmark

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

For single use only.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date is the last day of the month indicated.

This medicine does not require any 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 via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Irinotecan Glenmark

• The active substance is irinotecan hydrochloride trihydrate. Each millilitre (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 injections, sodium hydroxide (E524) and hydrochloric acid (E507) (for pH adjustment).

Appearance of the product and contents of the pack

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

40 mg/2 ml:
Amber glass type I flint vial, with a rubber stopper (bromobutyl rubber omniflex plus) and sealed with an aluminium flip-off cap in dark blue colour.

100 mg/5 ml:
Amber glass type I flint vial, with a rubber stopper (bromobutyl rubber omniflex plus) and sealed with an aluminium flip-off cap in light blue colour.

300 mg/15 ml:
Amber glass type I flint vial, with a rubber stopper (bromobutyl rubber omniflex plus) and sealed with an aluminium flip-off cap in dark blue colour.

500 mg/25 ml:
Amber glass type I flint vial, with a rubber stopper (bromobutyl rubber omniflex plus) and sealed with an aluminium flip-off cap in dark blue colour.

Pack 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 certain pack 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:
Glenmark Farmacéutica, S.L.U.
C/ Retama 7, 7th floor
28045 Madrid
Spain

Date of latest revision of this leaflet: February 2023.

Detailed information on this medicinal product 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 Glenmark

As with other antineoplastic agents, infusion of irinotecan must be prepared and handled with caution. Protective glasses, mask, and gloves must 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, rinse immediately with water.

As with all infusions, irinotecan must be prepared using aseptic techniques.

If any precipitation or condensation is observed in the vials or after dilution of the concentrate, the product must be discarded according to standard procedures for disposal of cytotoxic agents.

Preparation of the infusion solution

As with other infusions, irinotecan infusion must be prepared using aseptic techniques.

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

Aseptically withdraw the required amount of irinotecan concentrate from the vial using a calibrated syringe and inject it into a 250 mL infusion bag or bottle containing either 0.9% sodium chloride solution or 5% glucose solution. Mix the infusion solution thoroughly by gentle manual rotation.

Do not mix with other medicinal products.

Shelf life after dilution

Chemical and physical stability after dilution of the concentrate has been demonstrated for 28 days in 0.9% sodium chloride or 5% glucose solutions stored in LDPE or PVC containers at 5°C to 30°C, protected from light and moisture.

If the diluted solution is not protected from light and moisture, chemical and physical stability has been demonstrated for up to 3 days.

From a microbiological standpoint, the product should be used immediately. If not, storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 25°C, unless dilution has been carried out under validated, controlled aseptic conditions.

Warning on visible signs of deterioration

If visible particles are observed in the concentrate or in the infusion solution, the product must be discarded following procedures for disposal of cytotoxic agents.

Administration

For information regarding administration, please refer to the Summary of Product Characteristics (SmPC) of Irinotecan Glenmark.

Disposal

Disposal of unused medicinal product and all materials that have been in contact with it must be carried out in accordance with local regulations applicable to the disposal of cytotoxic agents.