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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

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

Leaflet contents

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

2. What you need to know before using Irinotecan Hospira

3. How to use Irinotecan Hospira

4. Possible side effects

5. How to store Irinotecan Hospira

6. Contents of the container and other information

1. What Irinotecan Hospira is and what it is 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 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 using Irinotecan Hospira

Do not use Irinotecan Hospira:

• if you have chronic inflammatory bowel disease or/or intestinal obstruction
• if you are allergic to irinotecan hydrochloride trihydrate or to any of the other ingredients of this medicine (listed in section 6)
• if you are breastfeeding (see section 2)
• if your bilirubin level is more than 3 times the upper limit of 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, varicella, 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 treatment with irinotecan.

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

Use special caution 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 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 not treated, it may lead to dehydration and serious electrolyte imbalances, which may be fatal. Your doctor will prescribe a medicine to help prevent or control this adverse effect. Make sure to obtain the medicine immediately so you have it at home when needed.

• Take the medicine as directed by your doctor at the first sign of loose or frequent stools.
• Drink plenty of water and/or electrolyte-containing fluids (mineral water, soda, or soup).

Call 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 your white blood cell count, mainly in the weeks following administration. This may increase your risk of developing an infection. Be sure to inform your doctor or nurse immediately if you have any signs of infection, such as fever (38°C or higher), chills, pain when urinating, 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 the 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 your teeth, or black, tarry stools.

Nausea (feeling unwell) and vomiting

You may experience nausea and vomiting on the day you receive this medicine or in the first few days afterward. Your doctor may give you medicines before treatment to help prevent nausea and vomiting. Your doctor may also prescribe anti-nausea medicines for you to take at home. Keep these medicines available for when you need them. Call your doctor if you cannot take fluids orally due to nausea and vomiting.

Acute cholinergic syndrome

This medicine may affect the part of your nervous system that controls body secretions, leading to a condition 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 notice any of these symptoms, as there are medicines 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 discontinue your treatment to manage this issue.

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 you also have bloating and loss of appetite.

Radiation therapy

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

Renal function

Cases of renal 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 ways to reduce risk factors (e.g., smoking, high blood pressure, high fat levels).

Vascular disorders

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

Other

This medicine may cause mouth or lip ulcers, often within the first few weeks of starting treatment. This may cause mouth pain, bleeding, or difficulty eating. Your doctor or nurse may suggest ways to reduce these symptoms, such as changing your eating habits or tooth brushing technique. 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 plan 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 Hospira

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 (succinylcholine)
• 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 receiving Irinotecan Hospira if you are already receiving or have recently received chemotherapy (and radiation therapy).

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

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

There may be additional 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 contraceptives 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 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 risk with this medicine 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 vision disturbances. 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 disorder, this medicine must not be given. Patients with HFI cannot break down fructose, which may lead to serious adverse effects.

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

This medicine contains 45 mg of sorbitol in each 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; hence, it is essentially “sodium-free”.

3. How to use Irinotecan Hospira

Follow exactly the administration instructions for this medicine given by your doctor. If in doubt, 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 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 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 intravenously (IV) and will be administered in 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 irinotecan administration.

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.

Currently, several treatment schedules are recommended for irinotecan. It is usually 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 status, 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. Symptoms of overdose may include some of the serious side effects listed in this leaflet.

If you forget to use Irinotecan Hospira

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 can cause adverse effects, although not everyone will experience them.

Some adverse effects could be serious. Contact your doctor immediately if you experience any of the following serious adverse effects (see section 2).

Seek emergency medical attention if you have any of the following 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 this case, inform the healthcare professional immediately. Medicines can be given to stop and/or reduce this early adverse effect).
  • Late diarrhea: begins more than 24 hours after receiving this medicine. Because of the risks of dehydration and electrolyte imbalance associated with diarrhea, it is important to stay in contact with healthcare professionals for monitoring and to receive recommendations regarding medications and dietary adjustments.

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 cause bruising or bleeding	Common	Very common
Abnormal liver function test results	Common	Very common
Infection	Common	Common
Low white blood cell count with fever	Common	Common
Constipation	Common	Common
Abnormal renal 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 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

• Colon enlargement

• Intestinal bleeding

• Inflammation of the large intestine

• Abnormal laboratory test results

• Intestinal perforation

• Fatty liver

• Skin reactions

• Reactions at the site where the medicine is administered

• Low blood potassium levels

• 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, consult 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 Hospira:

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.
• Shelf life: the shelf life in the unopened vial is 3 years. Once opened, vials must be used immediately, as they do not contain antimicrobial preservatives.
• Concentrate: store vials in the outer packaging to protect from light. Do not freeze.
• Diluted concentrate: for single use only. Any unused solution must be discarded.
• After dilution: chemical and physical in-use 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 standpoint, 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 normally not exceed 24 hours between 2 and 8 °C, unless dilution has taken place under controlled and validated aseptic conditions.

Do not use this medicine if visible particles are observed in the concentrate or in the infusion solution.

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 helps protect the environment.

6. Contents of the pack and other information

Composition of Irinotecan Hospira:

• The active substance is irinotecan hydrochloride trihydrate. Each millilitre (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 injections, sodium hydroxide, and hydrochloric acid (used to adjust pH) (see section 2).

Appearance of the product and contents of the pack

Irinotecan Hospira is a concentrate for solution for infusion (a concentrated solution that must be diluted before administration as a slow intravenous infusion).

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

The vials are enclosed in a protective plastic wrap to reduce the risk of spillage if the vials break—these are known as ONCO-TAIN® vials.

It is available in individual vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pfizer, S.L.

Avenida de Europa, 20 B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Manufacturer:

Pfizer Service Company BV

Hermeslaan 11

1932 Zaventem

Belgium

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Spain	Irinotecan Hospira
United Kingdom (Northern Ireland)	Irinotecan Hydrochloride
Portugal	Faultenocan

Date of the most recent review of this leaflet: September 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended for healthcare professionals only:

Instructions for healthcare personnel on the safe handling of Irinotecan Hospira

As with other antineoplastic agents, irinotecan infusion must be prepared and handled with caution. Protective gloves, mask, and eye protection should be worn.

Pregnant women should not handle cytotoxic drugs.

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

Preparation of the infusion solution

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

Using a graduated syringe, withdraw under aseptic conditions the required amount of Irinotecan Hospira concentrate for solution from the vial, and inject it into an infusion bag or bottle containing 250 mL of either 9 mg/mL (0.9%) sodium chloride or 50 mg/mL (5%) glucose, and no other diluent. The resulting solution for infusion should be carefully mixed by gentle manual agitation. Do not mix with other medicinal products.

Shelf life

After opening, irinotecan vials should be used immediately, as they contain no antimicrobial preservatives.

Stability after dilution:

Chemical and physical in-use stability has been demonstrated for up to 72 hours at 2–8°C in 50 mg/mL (5%) glucose or 9 mg/mL (0.9%) sodium chloride. From a microbiological standpoint, the product should be used immediately. If this is not possible, the storage duration and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2–8°C, unless dilution has been carried out under validated and controlled aseptic conditions.

Warning regarding visible signs of deterioration

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

Administration

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

Disposal:

Any unused medicinal product and all materials that have come into contact with it must be disposed of in accordance with local regulations governing the disposal of cytotoxic agents.