IRINOTECAN ACCORD 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

Irinotecan hydrochloride trihydrate

The name of the medicine is “Irinotecan Accord 20 mg/ml concentrate for solution for infusion”, but in the rest of the package leaflet it will be referred to as “Irinotecan Accord”.

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 get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

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

Irinotecan belongs to a group of medicines called cytostatics (cancer medicines). Irinotecan Accord is used for the treatment of advanced cancer of the colon and rectum in adults, both alone and in combination with other medicines. Irinotecan Accord 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.

Your doctor may use a combination of irinotecan with 5-fluorouracil/folinic acid (5-FU/FA)and bevacizumabto treat your colorectal cancer (colon or rectal cancer).Your doctor may use a combination of irinotecan with capecitabinewith or without bevacizumabto treat colon and rectal cancer.Your doctor may use a combination of irinotecan with cetuximabto treat a particular type of colorectal cancer (wild-type RAS)that expresses a protein called EGFR.

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

Do not use Irinotecan Accord if

• you are allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6).
• you have or have had chronic inflammatory bowel disease or intestinal obstruction
• you are breast-feeding
• you have severe liver disease (your bilirubin level is more than 3 times the upper limit of the normal range)
• you have severe bone marrow failure
• your general state of health is poor (WHO performance status greater than 2)
• you are using the herbal remedy St. John's Wort (Hypericum perforatum)
• If you are taking or have recently taken live attenuated vaccines (vaccines against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, flu) and for 6 months after stopping chemotherapy.

If you receive Irinotecan Accord in combination with other medicines, please make sure to also read the package leaflet of the other medicines regarding additional contraindications.

Warnings and precautions

Special caution is needed in elderly patients.

As irinotecan is a cancer medicine, it should be administered in a specialized unit and under the supervision of a qualified doctor experienced in the use of cancer medicines. The staff of the unit will explain the precautions you should take during and after treatment. This package leaflet helps you to remember them.

Before starting treatment with Irinotecan Accord, talk to your doctor if any of the following applies to you: • You have liver problems • You have kidney problems • You have asthma • You have ever received radiotherapy • You have had severe diarrhea or fever after being treated with irinotecan previously

• You have heart problems • You smoke, have high blood pressure or high cholesterol, as these may increase the risk of heart problems during treatment with irinotecan • You have been given or are to be given any vaccine • You are taking other medicines. Please consult the section "Other medicines and irinotecan"
• If you have Gilbert's syndrome, a hereditary condition that can cause high levels of bilirubin and jaundice (yellow skin and eyes)

1. The first 24 hours after administration of Irinotecan Accord

During administration of Irinotecan Accord (30-90 minutes) and immediately after administration, you may experience some of the following symptoms:

• Diarrhea
• Tearing
• Sweating
• Visual disturbance
• Abdominal pain
• Excessive salivation

Acute cholinergic syndrome

This medicine may affect the part of your nervous system that controls body secretions, leading to what is known as cholinergic syndrome. Symptoms may include runny nose, increased saliva, excessive tearing, sweating, flushing, abdominal cramps, and diarrhea. Inform your doctor or nurse immediately if you notice any of these symptoms, as there are medicines that can help control them.

1. From the day after treatment with Irinotecan Accord until the next treatment

During this period, you may experience various symptoms that can be severe and require immediate treatment and close monitoring.

Diarrhea

If you suffer from diarrhea after the first 24 hours after administration of irinotecan ("late diarrhea"), it could be severe. It often appears 5 days after administration. Diarrhea should be treated immediately and kept under close supervision. If left untreated, it can lead to dehydration and severe chemical imbalances, which can be life-threatening. Your doctor will prescribe a medicine to help prevent or control this side effect. Make sure you have the medicine readily available at home when you need it. Immediately after the first liquid stool, do the following:

1. Take the anti-diarrheal treatment that your doctor has prescribed and follow exactly the instructions that your doctor has given you. Do not change the treatment without consulting your doctor. The recommended anti-diarrheal treatment is loperamide (4 mg at the first intake and then 2 mg every 2 hours, also at night). This treatment should be continued for at least 12 hours after the last liquid stool. The recommended dose of loperamide should not be taken for more than 48 hours.
2. Drink plenty of water and rehydration fluids immediately (i.e., water, soda water, fizzy drinks, soup, or oral rehydration therapy)
3. Inform your doctor immediately that you are suffering from diarrhea and who is supervising your treatment. If you cannot speak to your doctor, contact the hospital unit that is supervising your treatment with irinotecan. It is very important that they know that the treatment has caused you diarrhea.

You must contact your doctor or the unit that is supervising your treatment immediately if:

• You suffer from nausea, vomiting, or fever as well as diarrhea
• You still have diarrhea 48 hours after starting anti-diarrheal treatment

Note:Only take the medicine for diarrhea that your doctor has prescribed and the fluids described above. Follow your doctor's instructions. Anti-diarrheal treatment should not be used to prevent future episodes of diarrhea, even if you have had late diarrhea in previous cycles.

Fever

If your temperature rises above 38°C, it may be a sign of infection, especially if you have also had diarrhea. If you get a fever (above 38°C), contact your doctor or the unit where you are being treated immediately so that they can give you the necessary treatment.

Nausea and vomiting

If you suffer from nausea and/or vomiting, contact your doctor or the hospital unit immediately. It is possible that your doctor will give you medicines before your treatment to help prevent nausea and vomiting. It is likely that your doctor will prescribe anti-nausea medicines that you can take at home. Have these medicines ready at home when you need them. Inform your doctor if you cannot take fluids by mouth due to nausea and vomiting.

Neutropenia

Irinotecan can cause a decrease in the number of white blood cells in your blood (neutropenia), which are important in fighting infections. Neutropenia is often seen during treatment with irinotecan and is reversible. Your doctor should perform regular blood tests to check these white blood cells. Neutropenia is severe and should be treated immediately and closely monitored. Make sure to inform your doctor or nurse immediately if you have symptoms of an infection, such as fever (38°C or higher), chills, pain when urinating, new cough, or sputum. Avoid being near people who are sick or have an infection. Inform your doctor if you develop symptoms of an infection.

Blood tests

It is likely that your doctor will perform blood tests before and during your treatment to check if there are any effects of the medicine on blood cell counts or blood chemistry test results. Based on the test results, you may need medicines to help treat the effects. It is possible that your doctor may also need to reduce or delay your next dose of this medicine or even stop treatment altogether. Keep all your appointments for medical visits and laboratory tests.

This medicine may decrease the number of platelets in the weeks following its use, 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 that contain aspirin, warfarin, or vitamin E. Inform your doctor immediately if you have unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black and tarry stools.

Pulmonary disorders

Rarely, people being treated with this medicine have severe pulmonary problems. Inform your doctor immediately if you have a new or worsening cough, difficulty breathing, and fever. Your doctor may need to stop treatment to treat this problem.

This medicine may increase the risk of having serious blood clots in the veins of the legs or lungs, which can travel 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

Inform your doctor if you have abdominal pain and cannot move your bowels, especially if you also have bloating and loss of appetite.

Radiation therapy

If you have recently received pelvic or abdominal radiotherapy, you may be at greater risk of developing bone marrow suppression. Please talk to your doctor before starting treatment with irinotecan.

Kidney function

There have been cases of worsening kidney function.

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

Vascular disorders

Irinotecan is rarely associated with alterations in blood flow (blood clots in the legs and lungs) and may rarely occur in patients with multiple risk factors.

Liver failure

Before starting treatment with Irinotecan and before each cycle, liver function (through blood tests) should be monitored.

Others

This medicine may cause mouth sores or sores on the lips, often within 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 this, such as changing the way you eat or brush your teeth. If necessary, your doctor may prescribe medicines to help soothe the pain.

To obtain information on contraception and breast-feeding, see the information provided below in the section Contraception, pregnancy, breast-feeding, and fertility.

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

If this medicine is used in combination with other anticancer medicines for your condition, make sure you also read the package leaflets of the other medicines.

If your doctor has informed you that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Other medicines and irinotecanInform your doctor if you are using or have recently used other medicines, including those bought without a prescription. This includes herbal medicines, vitamins, and minerals.

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

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

If you need an operation, inform your doctor or anesthetist that you are being treated with irinotecan, as it may affect the action of some medicines used during surgery.

Do not start or stop taking medicines while being treated with irinotecan without talking to your doctor first.

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

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

Contraception, pregnancy, breast-feeding, and fertilityContraception

If you are a woman of childbearing age, you must use an effective contraceptive method during and up to 6 months after stopping treatment.

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

Pregnancy

This medicine may cause problems with the fetus if taken 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 detected in human milk.

Breast-feeding should be discontinued during treatment with irinotecan. Ask your doctor before taking any 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 may preserve your ability to have children.

Driving and using machines

In some cases, irinotecan may cause side effects that affect your ability to drive and use tools and machines. Contact your doctor if you are not sure.

During the first 24 hours after administration of irinotecan, you may feel dizzy or have visual disturbances. If this happens, do not drive or use tools or machines.

Important information about some of the ingredients of Irinotecan AccordThis 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, you must not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

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

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

3. How to use Irinotecan Accord

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

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 with this medicine.

You may be given other medicines to prevent nausea, vomiting, diarrhea, and other side effects while you are receiving irinotecan. You may need to keep using these medicines for at least one day after the infusion of irinotecan.

Tell your caregivers if you feel burning, pain, or swelling around the intravenous needle when you are given irinotecan. If the medicine leaks out of the vein, it can cause damage to the injection site. If you experience pain or notice redness or swelling at the IV injection site while you are being given irinotecan, alert your healthcare professional immediately.

This medicine will be given to you as an infusion into your veins over a period of 30-90 minutes. The amount of infusion to be given will depend on your age, weight, and general health. It will also depend on any other treatment you may have received for your cancer. Your doctor will calculate your body surface area in square meters (m2).

• If you have been previously treated with 5-fluorouracil, you will normally be treated with irinotecan alone, starting with a dose of 350 mg/m2 every 3 weeks.

• If you have not received chemotherapy before, you will normally receive 180 mg/m2 of irinotecan every 2 weeks; followed by folinic acid and 5-fluorouracil.

• If you are being treated with irinotecan in combination with cetuximab, you will normally receive the same dose of irinotecan as that given in the previous cycles of the regimen containing irinotecan. Irinotecan should not be administered less than 1 hour after the end of the infusion with cetuximab.

Your doctor will adjust these doses depending on your condition and any side effects you may have.

If you receive more Irinotecan Accord than you should

It is unlikely that you will be given too much Irinotecan Accord. However, if this happens, you may have serious blood disorders and diarrhea. You should have close supportive care to prevent dehydration due to diarrhea and to treat infectious complications. You should talk to the doctor who administers the medicine.

If you miss a dose of Irinotecan Accord

It is very important to receive all scheduled doses. If you miss a dose, contact your doctor immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will inform you of the possible side effects and explain the risks and benefits of your treatment. Some of these side effects should be treated immediately.

See also information in the section “Warnings and precautions”

If you experience any of the following side effects after receiving the medicine, tell your doctor immediately. If you are not in the hospital, YOU MUST GO immediately.

• Allergic reactions. If you have wheezing, difficulty breathing, swelling, rash, or itching (especially affecting the whole body), contact your doctor or nurse immediately.
• Severe allergic reactions (anaphylactic/anaphylactoid reactions) may occur more frequently a few minutes after administration of the product: skin rash including itching of reddened skin, swelling of hands, feet, ankles, face, lips, mouth, or throat (which can cause difficulty swallowing or breathing) and you may also feel like fainting.
• Diarrhea (see section 2).
• Early diarrhea: occurs within the first 24 hours after receiving this medicine, accompanied by symptoms of runny nose, increased salivation, teary eyes, sweating, flushing, and abdominal cramps. (this can occur while the medicine is being administered. If this happens, tell your healthcare professional immediately. Medication can be given to stop and/or reduce this early side effect).
• Late diarrhea: occurs more than 24 hours after receiving this medicine. Due to the risk of dehydration and electrolyte imbalance with diarrhea, it is essential to be in contact with healthcare professionals for monitoring and for advice on medication and dietary changes.

Very common (may affect more than 1 in 10 people)

• Blood disorders: neutropenia (decrease in the number of some white blood cells), thrombocytopenia (decrease in the number of platelets in the blood), anemia (decrease in the number of red blood cells).
• Late diarrhea
• Nausea and vomiting
• Hair loss (hair grows back after treatment is finished)
• In combination therapy, transient increase in levels of some liver enzymes or bilirubin.

Common (may affect up to 1 in 10 people)

• Acute cholinergic syndrome: the main symptoms are early diarrhea and other symptoms such as abdominal pain; redness, itching, or tearing of the eyes (conjunctivitis); runny nose (rhinitis); low blood pressure; vasodilation; sweating, chills; general discomfort, dizziness; vision changes, pupil constriction; tearing of the eyes and increased salivation, which occur within the first 24 hours after the infusion of irinotecan.
• Fever, infections (including sepsis)
• Fever associated with a severe decrease in the number of some white blood cells
• Dehydration, usually associated with diarrhea and/or vomiting.
• Constipation
• Fatigue
• Increased levels of liver enzymes and creatinine in the blood.

Uncommon (may affect up to 1 in 100 people)

• Allergic reactions. If you have wheezing, difficulty breathing, sweating, swelling, rash, or itching (especially affecting the whole body), contact your doctor or nurse immediately.
• Mild skin reactions; mild reactions at the infusion site.
• Breathing difficulties
• Lung disease (interstitial lung disease)
• Intestinal obstruction
• Abdominal pain and inflammation, producing diarrhea (a condition known as pseudomembranous colitis)
• Rare cases of renal failure, low blood pressure, or heart or vascular failure have been observed in patients who experienced episodes of dehydration associated with diarrhea and/or vomiting or sepsis.

Rare (may affect up to 1 in 1,000 people)

• Severe allergic reactions (anaphylactic/anaphylactoid reactions) that may occur more frequently a few minutes after administration of the product: skin rash including itching of reddened skin, swelling of hands, feet, ankles, face, lips, mouth, or throat (which can cause difficulty swallowing or breathing) and you may also feel like fainting.
• Early effects such as muscle contraction or cramps and numbness (paresthesia).
• Gastrointestinal bleeding and colon inflammation, including the appendix.
• Intestinal perforation; anorexia (loss of appetite); abdominal pain; mucosal inflammation
• Pancreatitis.
• Increased blood pressure during and after administration.
• Decreased potassium and sodium levels in the blood, mainly related to diarrhea and vomiting.

Very rare (may affect up to 1 in 10,000 people)

• Transient speech disorders.
• Increased levels of some digestive enzymes that digest sugars and fats.

Unknown (frequency cannot be estimated from the 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 pale skin (a condition called hypovolemia).
• Allergic reaction
• Temporary speech disorders during or shortly after treatment.
• Numbness
• High blood pressure (during or after infusion)
• Heart problems*
• Lung disease that causes wheezing and shortness of breath (see section 2)
• Hiccup
• Intestinal blockage
• Enlarged colon
• Intestinal bleeding.
• Inflammation of the large intestine.
• Abnormal laboratory test results.
• Hole in the intestine.
• Fatty liver disease
• Skin reactions
• Reactions at the site where the medicine was administered.
• Low potassium levels in the blood.
• Low salt levels in the blood related mainly to diarrhea and vomiting
• Muscle cramps
• Kidney problems*
• Low blood pressure*
• Fungal infections
• Viral infections

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

If you receive irinotecan in combination with cetuximab, some of the side effects you may experience may also be related to this combination. These side effects may include a skin rash similar to acne. Therefore, make sure to also read the cetuximab package insert. If you receive irinotecan in combination with capecitabine, some of the side effects you may experience may also be related to this combination. These side effects may include: very frequently blood clots, frequently allergic reactions, heart attacks, and fever in patients with a low white blood cell count. Therefore, make sure to also read the capecitabine package insert. If you receive irinotecan in combination with capecitabineand bevacizumab, some of the side effects you may experience may also be related to this combination. Such side effects include: low white blood cell count, blood clots, high blood pressure, and heart attack. Therefore, make sure to also read the capecitabine and bevacizumab package inserts. If any of the side effects you suffer from is severe or if you notice any side effect not mentioned in this package insert, tell your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this package insert. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Irinotecan Accord

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

Do not freeze.

For single use.

This medicine does not require special temperature storage conditions. Keep this medicine in the original package to protect it from light.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Irinotecan Accord

• The active ingredient is irinotecan hydrochloride trihydrate
• 1 ml of concentrate contains 20 mg of irinotecan hydrochloride trihydrate equivalent to 17.33 mg of irinotecan.
• 1 vial of 2 ml contains 40 mg of irinotecan hydrochloride
• 1 vial of 5 ml contains 100 mg of irinotecan hydrochloride
• 1 vial of 15 ml contains 300 mg of irinotecan hydrochloride
• 1 vial of 25 ml contains 500 mg of irinotecan hydrochloride
• 1 vial of 50 ml contains 1000 mg of irinotecan hydrochloride
• The other components are sorbitol (E420), lactic acid, sodium hydroxide, hydrochloric acid, and water for injectable preparations

Product Appearance and Container Content

Irinotecan Accord 20 mg/ml concentrate for solution for infusion is a pale yellow transparent solution.

Container sizes: 2 ml, 5 ml, 15 ml, 25 ml, 50 ml. Not all container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,

95-200 Pabianice, Poland

or

Accord Healthcare single member S.A.

64th Km National Road Athens, Lamia, 32009,

Greece

This medicinal product is authorized in the following EEA Member States:

Date of the Last Revision of this Leaflet:October 2023

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

--------------------------------------------------------------------------------------------------------------------

Irinotecan Accord 20 mg/ml Concentrate for Solution for Infusion EFG

This information is intended for healthcare professionals only:

Instructions for Use – Cytotoxic

Handling of Irinotecan Accord

As with other antineoplastic agents, Irinotecan Accord should be handled with caution. Dilution should be performed under aseptic conditions, by qualified personnel, and in a designated area. Precautions should be taken to avoid skin and mucous membrane contact.

Protection Instructions for the Preparation of the Infusion Solution of Irinotecan:

1. A protective hood, as well as protective gloves and gown, should be used. If a protective hood is not available, goggles and a mask should be used.

1. Opened containers, such as injection vials and infusion bottles, and used cannulas, syringes, catheters, tubes, and cytostatic residues should be considered hazardous waste and disposed of in accordance with local regulations for the handling of HAZARDOUS WASTE.

1. In case of spillage, follow these instructions:

• protective clothing should be worn
• broken glass should be collected and disposed of in a HAZARDOUS WASTE container
• contaminated surfaces should be thoroughly washed with a large amount of cold water
• surfaces washed with water should be completely cleaned, and the materials used should be disposed of as HAZARDOUS WASTE

1. If irinotecan comes into contact with the skin, the affected area should be rinsed with a large amount of running water and then washed with water and soap. In case of contact with mucous membranes, the area of contact should be thoroughly washed with water. If you experience any discomfort, contact a doctor.

1. In case of eye contact with irinotecan, the eyes should be thoroughly washed with a large amount of water. Contact an ophthalmologist immediately.

Preparation of the Infusion Solution

Irinotecan Accord concentrate for solution for infusion is only for intravenous infusion after prior dilution in the recommended diluents, sodium chloride 0.9% infusion solution or glucose 5% infusion solution. The required amount of irinotecan concentrate for infusion should be aseptically withdrawn from the vial with a calibrated syringe and injected into a 250 ml infusion bag or bottle. The infusion solution should be thoroughly mixed by manual rotation.

After opening, the product should be diluted and used immediately.

The irinotecan solution is physically and chemically stable in sodium chloride 0.9% (w/v) and glucose 5% (w/v) infusion solutions for up to 28 days when stored in low-density polyethylene or PVC containers at 5°C or 25°C and protected from light. When exposed to light, the physical-chemical stability is 3 days. From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours between 2 and 8°C, unless the reconstitution/dilution (etc.) has been performed under controlled and validated aseptic conditions.

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

Irinotecan Accord should not be administered as an intravenous bolus or intravenous infusion with a duration of less than 30 minutes or more than 90 minutes.

Elimination

All materials used for the preparation, administration, or that come into contact with irinotecan should be disposed of in accordance with local regulations for the handling of cytotoxic compounds.