Irinotecan 20 mg / ml concentrate for solution for infusion – patient leaflet, side effects, dosage

1. WHAT IRINOTECAN IS AND WHAT IT IS USED FOR

Irinotecan is an anticancer medicine containing 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 cancer of the colon or rectum.

Irinotecan may be used alone in patients with metastatic cancer of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE IRINOTECAN

Do not use Irinotecan:

• if you are allergic to irinotecan hydrochloride

  trihydrate or any of the other ingredients of this medicine (listed in section 6).

• if you have chronic inflammatory bowel disease

  and/or bowel obstruction

• if you are a breast-feeding woman (see section 2)

• if your bilirubin level is higher than 3 times the upper

  limit of the normal range)

• if you have severe bone marrow failure

• if you are in poor general condition (WHO

  performance status higher than 2)

• if you are taking or have recently taken St John’s

  Wort (a herbal extract containing Hypericum)

• if you are to take or have recently taken live

  attenuated vaccines (vaccines against yellow fever, chicken pox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza) and during the 6 months after stopping chemotherapy.

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

Warnings and precautions

Talk to you doctor or pharmacist before using Irinotecan.

• if you have Gilbert’s syndrome, an inherited condition

  that can cause elevated bilirubin levels and jaundice (yellow skin and eyes).

Take special care with irinotecan. The use of irinotecan should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician qualified in the use of anticancer chemotherapy.

Diarrhoea

Irinotecan can cause diarrhoea, which in some cases may be severe. This may start a few hours or a couple of days after the medicine infusion. If left untreated, it could lead to dehydration and serious chemical imbalances, which can be life threatening. Your doctor will prescribe medicine to help prevent or control this side effect. Make sure you get the medicine right away, so that you will have it at home when you need it.

• Take the medicine as prescribed at the first sign of

  loose or frequent bowel movements.

• Drink large amounts of water and (or) salty drinks

  (fizzy water, soda or soup).

• Call your doctor or nurse know if you still have

  diarrhoea, especially if it lasts more than 24 hours, or if you get lightheaded, dizzy, or faint.

Neutropenia (decrease in some white blood cells)

This medicine can lower your white blood cell count, mainly in the weeks after the medicine is given. This can increase the risk of getting an infection. Be sure to let your doctor or nurse know right away if you have any signs of infection, such as fever (38 °C or higher), chills, pain when passing urine, a new cough, or bringing up sputum. Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Blood monitoring

Your doctor will likely test your blood before and during your treatment, to check for effects of the medicine on blood counts or on blood chemistry. Based on the test results, 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 appointments for doctor visits and lab tests. This medicine may lower your platelet count in the weeks after it is given, which can increase your risk of bleeding. Speak with your doctor before taking any medicines or supplements that might affect your body’s ability to stop bleeding, such as aspirin or aspirin-containing medicines, warfarin, or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools.

Nausea 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 medicine before your treatment to help prevent nausea and vomiting. Your doctor will likely prescribe anti- nausea medicines that you can take at home. Have these medicines on hand for when you need them. Call your doctor if you are unable to take fluids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

This medicine may affect part of your nervous system that controls body secretions, leading to what is known as cholinergic syndrome. Symptoms can include runny nose, increased saliva, excess tears in the eyes, sweating, flushing, abdominal cramps, and diarrhoea. Let your doctor or nurse know right away if you notice any of these symptoms, as there are medicines that can help control them.

Lung disorders

Rarely, people on this medicine have serious lung problems, tell your doctor right away if you have new or worsening cough, trouble breathing, and fever. Your doctor may need to stop your treatment to manage this problem.

This medicine may increase your risk of major 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. Tell your doctor right away if you notice chest pain, shortness of breath, or swelling, pain, redness, or warmth in an arm or leg.

Chronic intestinal inflammation and/or intestinal blockage

Call your doctor if you have pain in your belly and you cannot move your bowels, especially if you also have bloating and loss of appetite.

Irradiation therapy

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

Kidney function

Occurrences of kidney dysfunction have been reported.

Cardiac disorders

Inform your doctor if you suffer/suffered from heart disease or if you previously received anticancer medicines. Your doctor will monitor you closely and discuss with you how risk factors (for example smoking, high blood pressure and high fat content) can be reduced.

Vascular disorders

Irinotecan is rarely associated with blood flow disorders (blood clots in the vessels of your legs and lungs) and it may occur rarely in patients with multiple risks factors.

Others

This medicine may cause sores in the mouth or on the lips, often within the first few weeks after starting treatment. This can cause mouth pain, bleeding, or even trouble eating.

Your doctor or nurse can suggest ways to reduce this, such as changing the way you eat or how you brush your teeth. If needed, your doctor can prescribe medicine to help with the pain.

For contraception and breast-feeding information, refer to the information provided below under section Contraception, pregnancy, breast-feeding and fertility.

Tell your doctor or dentist that you are on this medicine if you are planning to have surgery or any procedure. If used in combination with other anticancer medicines for your condition, please make sure that you also read the leaflets for the other medicine.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Other medicines and Irinotecan:

Irinotecan can interact with a number of medicines and supplements, which may either raise or lower the level of the medicine in your blood. Tell your doctor or pharmacist if you are using, have recently used or might use any of the following:

• Medicines used to treat seizure (carbamazepine, phenobarbital, phenytoin and fosphenytoin)

• Medicines used to treat fungal infection

  (ketoconazole, itraconazole, voriconazole and posaconazole)

• Medicines used to treat bacterial infection

  (clarithromycine, erythromycin and telithromycine)

• Medicines used to treat tuberculosis (rifampicin and rifabutin)
• St. John’s Wort (a herbal dietary supplement)
• Live attenuated vaccines
• Medicines used to treat HIV (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• Medicines used to suppress your body’s immune system to prevent transplant rejection (cyclosporine and tacrolimus)
• Medicines used to treat cancer (regorafenib, crizotinib, idelalisib and apalutamide)
• Vitamin K antagonists (common blood thinner such as Warfarin)
• Medicines used to relax muscles used during general anaesthesia and surgery (suxamethonium)
• 5-fluorouracil/folinic acid
• Bevacizumab (a blood vessel growth inhibitor)
• Cetuximab (an EGF receptor inhibitor)

Tell your doctor, pharmacist, or nurse before being given Irinotecan if you are already having, or have recently had chemotherapy (and radiotherapy).

Don’t start or stop taking any medicines while you are on irinotecan without talking with your doctor first. This medicine can cause serious diarrhoea. Try to avoid laxatives and stool softeners while taking this medicine. There may be more medicines that interact with irinotecan. Check with 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 fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Contraception

If you are a woman of childbearing age, then you have to use effective contraception during and up to 6 months after stopping treatment.

As a man, you have to use effective contraception during and up to 3 months after stopping treatment. It is important to check with your doctor about what kinds of birth control can be used with this medicine.

Pregnancy

This medicine may cause problems with the foetus if taken at the time of conception or during pregnancy. Before initiating treatment, your doctor will ensure that you are not pregnant.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Breast-feeding

Irinotecan and its metabolite were measured in human milk. Breast-feeding should be discontinued for the duration of your treatment with this medicine. If you are breast-feeding, ask your doctor or pharmacist for advice before taking this medicine.

Fertility

No studies have been done, nevertheless, this medicine may affect fertility. Prior to taking this medicine talk with your doctor about the possible risk with this medicine and the options that may preserve your ability to have children.

Driving and using machines

You may notice that you are dizzy and/or have trouble with your vision in the first 24 hours or so after you take this medicine. Do not drive or operate machinery if you have this side effect.

This medicine contains sorbitol.

This medicine contains a sugar (sorbitol). Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not receive this medicine. Patients with HFI cannot break down fructose, which may cause serious side effects.

You must tell your doctor before receiving this medicine if you (or your child) have HFI or if your child can no longer take sweet foods or drinks because they feel sick, vomit or get unpleasant effects such as bloating, stomach cramps or diarrhoea.

This medicine contains 45 mg sorbitol in each mL which is equivalent to 90 mg/2 ml, 225 mg/5 ml, and 675 mg/15 ml and 1125 mg/25 ml.

This medicine contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per ml of solution, that is to say essentially ‘sodium-free’.

3. HOW TO USE IRINOTECAN

Always use this medicine exactly as your doctor has told you. Check with your doctor is you are not sure. Irinotecan will be given to you by healthcare professionals.

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

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

The amount of Irinotecan that 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 condition being treated.

Your doctor will determine your dose and schedule. Irinotecan is injected into a vein through an intravenous route (IV). You will receive this injection in a clinic or hospital setting. Irinotecan must be given slowly, and the IV infusion can take up to 90 minutes to complete. You may be given other medications to prevent nausea, vomiting, diarrhoea, and other side effects while you are receiving Irinotecan. You may need to keep using these medicines for at least a day after your Irinotecan injection. Tell your care givers if you feel any burning, pain, or swelling around the IV needle when Irinotecan is injected. If the medicine escapes from the vein it can cause tissue damage. If you experience pain or notice redness or swelling at the IV site while you are receiving Irinotecan, alert your healthcare professional immediately. There are currently several treatment schedules recommended for Irinotecan. It is usually given either once every 3 weeks (irinotecan given alone) or once every 2 weeks (irinotecan given in combination with 5FU/ FA chemotherapy). The dose will depend on a number of factors, including the treatment schedule, your body size, your age and general health, your blood counts, how well your liver is working, whether you have had radiation to your abdomen/pelvis, and whether you have any side effects such as diarrhoea.

Only your doctor may assess the duration of treatment.

If you are given too much Irinotecan

Seek emergency medical attention. Overdose symptoms may include some of the serious side effects listed in this medication guide.

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Handling:

As with other antineoplastic/cytotoxic agents, Irinotecan must be prepared and handled with caution. The use of goggles, mask and gloves is mandatory.

In case of skin contact with the concentrate or diluted solution, wash immediately and thoroughly with soap and water. If Irinotecan solution or infusion solution come into contact with the mucous membranes, wash immediately with water.

Instructions for dilution:

As with any other injectable drugs, Irinotecan solution must be prepared aseptically.

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

Aseptically withdraw the required amount of Irinotecan 20 mg/ ml, concentrate for solution for infusion from the vial with a calibrated syringe and inject into a 250 ml infusion bag or bottle containing either 0.9 % sodium chloride solution or 5% glucose solution. The infusion should then be thoroughly mixed by manual rotation.

Instructions for protection for dilution:

The preparation should be performed in a defined area for manipulation of the drug (preferably under system of vertical laminar air flow). The working area should be protected by coating with disposable absorbent paper and plastic.

Protective clothing should be used: protective goggles, hair cap, gown and gloves and disposable masks. PACKAGE LEAFLET: INFORMATION FOR THE USER

Irinotecan 20 mg/ml

Concentrate for solution for infusion

irinotecan hydrochloride, trihydrate

The following information is intended for healthcare professionals only:

Irinotecan 20 mg/ml

Concentrate for solution for infusion

irinotecan hydrochloride, trihydrate

If you miss an appointment to get Irinotecan

Call your doctor for instructions if you miss an appointment for your Irinotecan injection.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some side effect could be serious. You must immediately contact your doctor if you experience any of those following serious side effects (see section 2).Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

• diarrhoea (see section 2)

• Early diarrhoea: Occurring within 24 hours of

  receiving this medicine, accompanied by symptoms runny nose, increased salivation, watery eyes, sweating, flushing, abdominal cramping. (This can occur while the medicine is being administered. If so, alert your healthcare professional promptly. Medication can be given to stop and/or lessen this early side effect).

• Late diarrhoea: Occurring greater than 24 hours of

  receiving this medicine. Because of concerns of dehydration and electrolyte imbalances with diarrhoea it is important to be in contact with health care professionals for monitoring, and for medication and diet modifications advice.

Talk to your doctor or nurse if you experience any of the symptoms below:

Symptoms Frequency* of

occurrence in Monotherapy

Frequency^† of occurrence in Combination Therapy

Abnormally low

number of white

blood cells which

could put you

atincreased risk for

infection

Very common Very common

Low number of red

blood cells causing

tiredness and

shortness of breath

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 Hair loss (reversible) Very common Very common Inflammation of

mucous membranes

Very common Very common

Fever Very common Common Feeling weak and

having no energy

Very common Very common

Low number of

platelets (blood

cells that help with

clotting) which may

cause bruising or

bleeding

Common Very common

Abnormal liver

function test values

Common Very common

Infection Common Common Low number of

white blood cells

with fever

Common Common

Difficulty in passing

stools

Common Common

Abnormal kidney

function test values

Common ot

reported

* Very common: may affect more than 1 in 10 people ^† Common: may affect up to 1 in 10 people

Not known: frequency cannot be estimated from available data

• Severe, persistent or bloody diarrhoea (which may

  be associated with stomach pain or fever) caused by bacteria called Clostridium difficile

• Blood infection
• Dehydration (due to diarrhoea and vomiting)

• Dizziness, rapid heart beat and pale skin (a condition

  called hypovolaemia)

• Allergic reaction
• Temporary speech disorders during or shortly after treatment
• Pins and needles
• High blood pressure (during or after infusion)
• Heart problems*

• Lung disease causing wheezing and shortness of

  breath (see section 2)

• Hiccups
• Intestinal blockage
• Enlarged colon
• Bleeding from the bowels
• Inflammation of the large intestine
• Abnormal lab test results
• Hole in the intestine
• Fatty liver disease
• Skin reactions
• Reactions at the site where the medicine was administered
• Low level of potassium in the blood

• Low level of salt in the blood mostly related with

  diarrhoea and vomiting

• Muscle cramps
• Kidney problems*
• Low blood pressure*
• Fungal infections
• Viral infections

* Infrequent cases of these events have been observed in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or infections of the blood.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website:

www.mhra.gov.uk/ yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE IRINOTECAN

Keep this medicine out of the sight and reach of children. Store below 25°C.

Do not refrigerate or freeze.

Store in the original package in order to protect from light.

After opening:

Chemical and physical in-use stability of the concentrate in the punctured vial has been demonstrated for 28 days at room temperature, exposed or protected from light, and for 28 days at 2-8°C, when protected from light. From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

After dilution

After dilution with 5% glucose, physical and chemical stability was demonstrated for 24 hours, when stored between 2-8ºC and for 12 hours when stored at 25±2ºC, protected from light.

After dilution with 0.9% sodium chloride, physical and chemical stability was demonstrated for 24 hours, when stored between 2-8ºC and for 12 hours when stored at 25±2ºC, protected from light.

Irinotecan should be diluted.

From a microbiologic point of view, unless the method of dilution precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of user.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

All materials used for dilution and administration should be disposed of according to hospital standard procedures applicable to cytotoxic agents.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Irinotecan contains

The active substance of Irinotecan is irinotecan hydrochloride, trihydrate.

1 ml of concentrate contains 20 mg of irinotecan hydrochloride, trihydrate (equivalent to 17.33mg/ml of irinotecan).

One vial of 2 ml contains 40 mg of irinotecan hydrochloride, trihydrate.

One vial of 5 ml contains 100 mg of irinotecan hydrochloride, trihydrate.

One vial of 15 ml contains 300 mg of irinotecan hydrochloride, trihydrate.

One vial of 25 ml contains 500 mg of irinotecan hydrochloride, trihydrate.

The other ingredients are sorbitol (E420), lactic acid, sodium hydroxide and/or hydrochloric acid (for pH adjustment) and water for injections.

Irinotecan is a yellow clear solution.

What Irinotecan looks like and contents of the pack

Amber glass vial, with rubber stopper and aluminium flip-off cap.

Package size:

Pack with 1 vial of 2 ml

Pack with 1 vial of 5 ml

Pack with 1 vial of 15 ml

Pack with 1 vial of 25 ml

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, nº 8, 8A – 8B

Fervença

2705 – 906 Terrugem SNT

Portugal

Manufacturer:

Thymoorgan Pharmazie GmbH

Schiffgraben 23

D-38690 Goslar

Germany

This leaflet was last revised in October 2025.

P1564

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Open containers such as bottles of the injection and infusion bottles and tubes, syringes, catheters and tubes used, as well as cytotoxic waste, should be considered hazardous waste and be disposed of in accordance with local guidelines for handling of HAZARDOUS waste.

In case of spillage, protective clothing should be used. Broken glass should be collected and placed in hazardous waste containers. The contaminated surfaces should be properly rinsed with abundant amounts of cold water and thoroughly cleaned. The materials used for cleaning should be disposed of as hazardous waste.

In case of Irinotecan come into contact with the skin, the area should be rinsed profusely with running water and then washed with soap and water. In case of contact with mucous membranes, wash thoroughly the affected area contacted with water. If you feel some unease, contact a doctor.

In case of eye contact with Irinotecan, wash them thoroughly with plenty of water. Contact an ophthalmologist immediately.

Disposal: All materials used for dilution and administration should be disposed of according to hospital standard procedures applicable to cytotoxic agents.