IRINOTECAN HOSPIRA 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Irinotecan Hospira 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.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

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

Irinotecan Hospira 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 may be used alone 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 Hospira

Do not use Irinotecan Hospira:

• if you have a chronic inflammatory bowel disease or intestinal obstruction.
• if you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding (see section 2).
• if 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 anticancer 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 treatment with irinotecan.

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

Be 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 physician experienced in the use of antineoplastic chemotherapy.

Diarrhea

Irinotecan can cause diarrhea, which can sometimes be severe. This can start a few hours or a couple of days after infusion of the medicine. If not treated, it can lead to dehydration and severe chemical imbalances, which can be fatal. Your doctor will prescribe a medicine to help prevent or control this side effect. Make sure to get the medicine right away 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 (e.g., sports drinks, clear soups).

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 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, painful urination, 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. Depending on the results of the tests, 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 doctor's appointments and laboratory tests.

This medicine can reduce the count of platelets in the weeks following administration, which can increase 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 medicines containing aspirin, warfarin, or vitamin E. Inform your doctor immediately if you have unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black and tarry stools.

Nausea (feeling sick) 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 when you need them. Call your doctor if you cannot take fluids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

This medicine can affect the part of your nervous system that controls body secretions, leading to a condition called cholinergic syndrome. Symptoms can include runny nose, increased salivation, excessive tear production, 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 severe lung problems. Inform your doctor immediately if you start coughing or your cough gets worse, 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

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 to reduce risk factors (e.g., smoking, high blood pressure, and high fat content).

Vascular disorders

Irinotecan is rarely associated with vascular 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 ulcers on the lips, 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 breast-feeding, see the information provided later in the section Contraception, pregnancy, breast-feeding, and fertility.

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

If you are using this medicine in combination with other anticancer medicines to treat your disease, make sure to also read the package leaflet of the other medicines.

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

Other medicines and Irinotecan Hospira

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 rejection in transplants (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).

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

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

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

There may be more medicines that interact with irinotecan. Talk to your doctor, pharmacist, or nurse about your other medicines, herbal products, and supplements, and whether alcohol can cause problems with this medicine.

Contraception, pregnancy, breast-feeding, and fertility

Contraception

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

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

Pregnancy

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

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

Breast-feeding

Irinotecan and its metabolite were measured in breast milk. Breast-feeding 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 administration of this medicine, you may feel dizzy or have changes in vision. If you have 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, you must not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Talk to your doctor before receiving this medicine if you (or your child) have HFI or cannot take foods or drinks containing sugars because they cause dizziness, vomiting, or effects 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, and 1125 mg/25 mL.

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 Hospira

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are unsure, consult your doctor again.

Irinotecan will be administered to you by healthcare professionals.

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

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

The amount of irinotecan you receive will depend on many factors, including your height and weight, your overall health, or other health problems, and the type of cancer or disease 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 administration of 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 can cause tissue damage. If you feel pain or notice redness or swelling at the injection site while receiving irinotecan, inform the healthcare professional immediately.

Several treatment schedules are currently recommended for irinotecan. It is usually administered once every 3 weeks (irinotecan alone) or once every 2 weeks (irinotecan in combination with 5FU/FA chemotherapy). The dose will depend on several factors, including the treatment schedule, your body size, age, and overall 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 Hospira than you should:Seek emergency medical attention. The symptoms of overdose may include some of the serious side effects listed in this leaflet.

If you miss a dose of Irinotecan Hospira

Consult your doctor for instructions if you miss an appointment for 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: starts within 24 hours after receiving this medicine and is accompanied by symptoms such as: runny nose, increased salivation, tearing of the eyes, sweating, flushing, abdominal cramps (this can occur while the medicine is being administered. In this case, notify the healthcare professional immediately. Medicines can be administered to stop and/or reduce this early adverse effect).
  • Late diarrhea: starts more than 24 hours after receiving this medicine. Due to dehydration and electrolyte imbalance problems with diarrhea, it is essential to be in contact with healthcare professionals for control and to obtain recommendations on medications and dietary 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 infusion)
• 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 Hospira:

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.
• Validity: the validity period in the closed vial is 3 years. Once opened, the vials must be used immediately since they do not contain antimicrobial preservatives.
• Concentrate: store the vials in the outer packaging to protect them from light. Do not freeze.
• Diluted concentrate: for single use only. The unused solution must be discarded.
• After dilution: chemical and physical stability has been demonstrated in glucose 50 mg/mL (5%) and sodium chloride 9 mg/mL (0.9%) for 72 hours at 2-8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has taken place in validated and controlled aseptic conditions.

Do not use this medicine if you observe visible particles in the concentrate or in the infusion solution.

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

6. Package Contents and Additional Information

Composition of Irinotecan Hospira:

• The active ingredient is irinotecan hydrochloride trihydrate. Each milliliter (mL) of solution contains 20 milligrams (mg) of irinotecan hydrochloride trihydrate, equivalent to 17.33 mg of irinotecan.
• The other components are sorbitol (E420), lactic acid, water for injectable preparations, sodium hydroxide, and hydrochloric acid (used to adjust the pH) (see section 2).

Appearance of the Product and Package Contents

Irinotecan Hospira is a concentrate for solution for infusion (concentrated solution that is diluted to make a solution that is administered by slow infusion by drip).

The medicine comes in glass containers called vials, which contain 2 mL, 5 mL, and 25 mL of irinotecan hydrochloride trihydrate.

The vials are wrapped in protective plastic to reduce the risk of spills if the vials break - these are called ONCO-TAIN® vials.

It is presented in individual vials. Not all presentations may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing authorization holder:

Pfizer, S.L.

Avenida de Europa, 20 B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Manufacturer

Pfizer Service Company BV

Hoge Wei 10

1930 Zaventem

Belgium

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Date of the last revision of this prospectus: September 2023

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

This information is intended only for healthcare professionals:

Instructions for personnel on the safe handling of Irinotecan Hospira

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

Pregnant women should not handle cytotoxics.

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

Preparation for the Infusion Solution

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

Using a graduated syringe, extract the necessary amount of Irinotecan Hospira concentrate for solution from the vial, under aseptic conditions, and inject it into a 250 mL bag or bottle of 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) glucose, only. The infusion solution should be mixed carefully by manual rotation. Do not mix with other medicines.

Validity Period

Once opened, the irinotecan injection vials must be used immediately since they do not contain antimicrobial preservatives.

Stability after dilution:

Chemical and physical stability has been demonstrated in glucose 50 mg/mL (5%) and sodium chloride 9 mg/mL (0.9%) for 72 hours at 2-8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has taken place in validated and controlled aseptic conditions.

Warning about Visual Signs of Deterioration

If you observe visible particles in the concentrate or in the infusion solution, 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 Hospira.

Elimination:

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