Irinotecan eugia

Package leaflet: Information for the patient

Irinotecan Eugia, 20 mg/mL, concentrate for solution for infusion
Irinotecani hydrochloridum trihydricum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

1. What Irinotecan Eugia is and what it is used for
2. Important information before using Irinotecan Eugia
3. How to use Irinotecan Eugia
4. Possible side effects
5. How to store Irinotecan Eugia
6. Contents of the pack and other information

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

Irinotecan Eugia is an anticancer medicine containing the active substance
irinotecan hydrochloride trihydrate.
Irinotecan hydrochloride trihydrate inhibits the growth and spread of cancer cells in the
body. Irinotecan Eugia is indicated in combination with other medicines for the treatment of
patients with advanced colorectal cancer (colon and rectum) or metastatic colorectal cancer.
Irinotecan Eugia may be used as a single agent (monotherapy) in patients with metastatic
colorectal cancer (colon and rectum) in whom the disease has recurred or worsened after initial
treatment with 5-fluorouracil.

2. Important information before using Irinotecan Eugia

When not to use Irinotecan Eugia

• if the patient is allergic to irinotecan hydrochloride trihydrate or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has chronic inflammatory bowel disease and (or) bowel obstruction;
• if the patient is breastfeeding (see section 2);
• if the patient's blood bilirubin level exceeds 3 times the upper limit of normal;
• if the patient has severe bone marrow failure;
• if the patient is in poor general condition (performance status according to WHO classification > 2);
• if the patient is taking or has recently taken products containing St. John’s wort (Hypericum perforatum);
• if the patient is to receive or has recently received a live attenuated vaccine (vaccines against yellow fever, varicella, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, influenza) and within 6 months after completion of chemotherapy.

If the patient is receiving Irinotecan Eugia together with other medicines, please also refer to the information provided in the package leaflets of those medicines regarding additional contraindications.

Warnings and precautions

Before using Irinotecan Eugia, discuss this with your doctor, pharmacist, or nurse.

Extreme caution should be exercised during treatment. Irinotecan Eugia should be administered only in a hospital ward specialized in cytotoxic chemotherapy and under the supervision of a physician experienced in anticancer therapy.

Diarrhoea

Irinotecan Eugia may cause diarrhoea, which in some cases may be severe. It may occur several hours or several days after infusion. Untreated diarrhoea may lead to dehydration and severe electrolyte imbalances, which may be life-threatening. Your doctor will prescribe a medication to prevent or control this adverse effect. Ensure that you have received this medication so that you can take it home and use it if necessary. You should:

• take the anti-diarrhoeal medication prescribed by your doctor at the first sign of loose stools or frequent bowel movements;
• drink large amounts of water and (or) salty fluids (soda water, carbonated drinks, or soups);
• inform your treating doctor or nurse if diarrhoea persists (especially if it lasts longer than 24 hours), or if you feel confused, dizzy, or faint.

Neutropenia (reduced number of certain white blood cells)

This medicine may reduce the number of white blood cells (mainly within weeks after administration), increasing the risk of developing infections. Immediately inform your doctor or nurse if you experience any signs of infection such as fever (38°C or higher), chills, pain during urination, cough, or production of sputum. Avoid close contact with people who are ill or have infections. Inform your doctor immediately if you develop signs of infection.

Blood tests

Your doctor will order blood tests before starting treatment and during therapy to monitor the effect of the medicine on blood cell counts or chemical composition of blood. Based on the results, your doctor may decide to administer medications to treat any abnormalities detected. It may also be necessary to reduce or delay the next dose, or even discontinue treatment. Please adhere to the recommended follow-up appointments and laboratory tests.

This medicine may reduce the number of platelets (within weeks after administration), increasing the risk of bleeding. Consult your doctor before taking any medication or supplement that may affect blood clotting (such as acetylsalicylic acid or products containing it, warfarin, or vitamin E). Seek immediate medical advice if you notice unusual bruising or bleeding, such as nosebleeds, bleeding gums during tooth brushing, or black, tarry stools.

Nausea and vomiting

Nausea and vomiting may occur on the day of administration or within the first few days after receiving the medicine. Before receiving Irinotecan Eugia, you may be given medication to prevent nausea and vomiting. Your doctor may also prescribe an antiemetic medicine for home use. Take it as needed. Contact your doctor if nausea and vomiting prevent you from drinking fluids orally.

Acute cholinergic syndrome

This medicine may affect part of the nervous system regulating certain bodily secretions, causing what is known as cholinergic syndrome. Symptoms include runny nose, increased salivation, excessive tearing, sweating, skin flushing, abdominal cramps, and diarrhoea. Inform your doctor or nurse immediately if any of these symptoms occur, as there are medications available to help control them.

Lung disorders

Severe lung disorders may rarely occur in some patients receiving this medicine. If you develop cough, worsening cough, difficulty breathing, or fever, inform your doctor immediately. Your doctor may decide to interrupt treatment until these symptoms resolve.

This medicine may increase the risk of blood clots in veins (e.g., in the legs), which may travel to other parts of the body such as the lungs or brain. Inform your doctor immediately if you experience chest pain, shortness of breath, or swelling, pain, redness, or warmth in an arm or leg.

Chronic inflammatory bowel disease and (or) bowel obstruction

Contact your doctor if you experience abdominal pain and constipation, especially if associated with bloating and loss of appetite.

Radiation therapy

Patients who have recently undergone pelvic or abdominal radiotherapy may have an increased risk of bone marrow suppression. Discuss this with your doctor before starting Irinotecan Eugia.

Kidney function

Kidney function disorders have been reported.

Heart disorders

Inform your doctor if you have or have had heart disease or previously received anticancer medicines. Your doctor will closely monitor your condition and discuss ways to reduce risk factors (such as smoking, high blood pressure, and high blood lipid levels).

Vascular disorders

Rarely, Irinotecan Eugia has been associated with blood flow disorders (blood clots in vessels of legs and lungs), particularly in patients with multiple risk factors.

If the patient has Gilbert’s syndrome, a hereditary condition that may cause elevated bilirubin levels and jaundice (yellowing of the skin and eyes).

Other

This medicine may cause ulceration of the mouth or lips, often within the first few weeks of treatment. This may cause mouth pain, bleeding, or difficulty eating. Your doctor or nurse may suggest ways to relieve symptoms, such as changing eating or toothbrushing habits. If necessary, your doctor may prescribe pain-relieving medication.

Information on contraception, pregnancy, breastfeeding, and fertility is provided below under the section
“Contraception, pregnancy, breastfeeding, and effects on fertility.”

If you are scheduled for surgery or any medical or dental procedure, inform your doctor or dentist that you are receiving Irinotecan Eugia.

If you are receiving Irinotecan Eugia together with other medicines, please also read the package leaflets of those medicines.

If you have been diagnosed with intolerance to certain sugars, inform your doctor before administration of this medicine.

Irinotecan Eugia and other medicines

Irinotecan Eugia may interact with other medicines and supplements, potentially increasing or decreasing its blood concentration. Inform your doctor if you are taking, have recently taken, or plan to take any of the following medicines:

• antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, and fosphenytoin)
• antifungal agents (ketoconazole, itraconazole, voriconazole, and posaconazole)
• antibacterial agents (clarithromycin, erythromycin, and telithromycin)
• antituberculosis drugs (rifampicin and rifabutin)
• St. John’s wort (herbal dietary supplement)
• live attenuated vaccines
• HIV medications (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• immunosuppressants used to prevent organ transplant rejection (cyclosporine and tacrolimus)
• anticancer drugs (regorafenib, crizotinib, idelalisib, and apalutamide)
• vitamin K antagonists (commonly used anticoagulants such as warfarin)
• muscle relaxants used during general anaesthesia and surgery (suxamethonium)
• 5-fluorouracil/folinic acid
• bevacizumab (an anti-angiogenic cancer drug)
• cetuximab (an epidermal growth factor receptor inhibitor, EGFR).

Before receiving Irinotecan Eugia, inform your doctor, pharmacist, or nurse if you are currently or have recently undergone chemotherapy (and radiotherapy).

During treatment with Irinotecan Eugia, do not start or stop taking any other medicine without first discussing it with your doctor.

This medicine may cause severe diarrhoea. Avoid taking laxatives or stool softeners during treatment.

Many other medicines may interact with Irinotecan Eugia. Ask your doctor, pharmacist, or nurse about other medicines, herbal remedies, and supplements you are taking, and about possible problems related to alcohol consumption during treatment.

Contraception, pregnancy, breastfeeding, and effects on fertility

Contraception

Women of childbearing potential must use effective contraception during treatment and for 6 months after completion of therapy.

Men must use effective contraception during treatment and for 3 months after completion of therapy. It is important to consult your doctor about which types of contraception are suitable with this medicine.

Pregnancy

This medicine may cause harm to the unborn child if taken during conception or pregnancy. Before starting treatment, your doctor will confirm that you are not pregnant.

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

Breastfeeding

Irinotecan and its metabolite have been detected in human 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, but this medicine may affect fertility. Before taking this medicine, discuss with your doctor the potential risks associated with this medicine and options that may affect your ability to have children.

Driving and using machines

Within the first 24 hours after receiving Irinotecan Eugia, you may experience dizziness and (or) blurred vision. If these occur, do not drive or operate machinery.

Irinotecan Eugia contains sorbitol

This medicine contains a sugar (sorbitol). Sorbitol is a source of fructose. If you or your child has previously been diagnosed with hereditary fructose intolerance, a rare genetic disorder, you or your child must not take this medicine. In patients with hereditary fructose intolerance, the body cannot break down fructose contained in this medicine, which may lead to severe adverse effects. Inform your doctor before taking this medicine if you or your child has hereditary fructose intolerance or if your child should avoid sweet foods or drinks due to nausea, vomiting, or adverse effects such as bloating, stomach cramps, or diarrhoea.

Irinotecan Eugia contains sodium

Irinotecan Eugia contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to use Irinotecan Eugia

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your
doctor.
Irinotecan Eugia is administered by trained medical personnel.
Before the first dose of Irinotecan Eugia is given, your doctor may order a DNA test for the patient.
Some people may, for genetic reasons, be more susceptible to certain side effects of the medicine.
The dose given depends on many factors, including the patient's height and body weight, general
health or other medical conditions, type of cancer or disease being treated. The doctor will determine
the dosage and treatment schedule.
Irinotecan Eugia is injected intravenously (IV) into a vein. The patient will receive this injection at
a clinic or hospital. Irinotecan must be administered slowly, and the intravenous infusion may last
up to 90 minutes.
The patient may be given other medicines to prevent nausea, vomiting, diarrhoea, and other side
effects during treatment with Irinotecan Eugia. It may be necessary to continue taking these
medicines for at least one day after receiving Irinotecan Eugia injection.
Inform the medical staff immediately if, after the injection, the patient experiences burning, pain,
or swelling around the intravenous needle. If the medicine leaks out of the vein, it may cause tissue
damage. If pain, redness, or swelling occurs at the intravenous injection site during administration,
notify the doctor 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/FA chemotherapy). The dose will depend on many factors, including the treatment
schedule, the patient's body surface area, age and general health, blood counts, liver function,
whether or not abdominal and/or pelvic radiotherapy is being administered, and the presence (or
absence) of side effects such as diarrhoea.
Only the doctor can determine the duration of treatment.
Taking more Irinotecan Eugia than prescribed
Seek immediate medical help. Symptoms of overdose may include some of the severe side effects
listed in this leaflet.
Missing a dose of Irinotecan Eugia
If an appointment for receiving a dose of Irinotecan Eugia is missed, consult the doctor for guidance
on how to proceed.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist,
or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Some of the adverse reactions may be severe. If the patient experiences any of the severe adverse reactions listed below, contact a doctor immediately (see section 2).
Seek urgent medical help if any symptoms of an allergic reaction occur: hives, difficulty breathing, swelling of the face, lips, tongue, or throat.

• Diarrhoea (see section 2).
• Early-onset diarrhoea: begins within 24 hours of receiving this medicine and may be accompanied by the following symptoms: runny nose, increased salivation, lacrimation, sweating, skin flushing, abdominal cramps. (Early-onset diarrhoea may occur during infusion. In such a case, it must be reported immediately to medical staff. The patient may be given a medicine to stop or alleviate this early adverse reaction).
• Delayed-onset diarrhoea: begins more than 24 hours after administration of the medicine. Due to the risk of dehydration and electrolyte imbalance associated with it, it is important that the patient contacts medical staff for monitoring and advice regarding treatment and dietary modifications.

Contact a doctor or nurse if any of the following symptoms occur:

Very common: may occur in more than 1 in 10 people
Common: may occur in less than 1 in 10 people
Frequency not known: cannot be estimated based on available data

• severe, persistent or bloody diarrhoea (which may be associated with abdominal pain or fever) caused by Clostridium difficile bacteria
• blood infection
• dehydration (due to diarrhoea and vomiting)
• dizziness, rapid heartbeat and pale skin (so-called hypovolemia)
• allergic reaction
• temporary speech disturbances during or shortly after administration of the medicine
• tingling
• high blood pressure (during or after infusion)
• heart function disorders
• lung disease causing wheezing and shortness of breath (see section 2)
• hiccups
• intestinal obstruction
• enlargement of the colon
• gastrointestinal bleeding
• inflammation of the large intestine
• abnormal laboratory test results
• intestinal perforation
• fatty liver
• skin reactions
• reactions at the site of administration
• low blood potassium levels
• low blood salt levels, mainly due to diarrhoea and vomiting
• muscle cramps
• kidney function disorders
• low blood pressure
• fungal infections
• viral infections

Rare cases of these adverse effects have been observed in patients with episodes of dehydration associated with diarrhoea and/or vomiting or blood infections.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions allows more information on the safety of the medicine to be collected.
Adverse reactions can also be reported to the marketing authorization holder.

5. How to store Irinotecan Eugia

Keep this medicine out of the sight and reach of children.
There are no special requirements regarding storage temperature. Store the vials in the
outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the carton and vial following: EXP.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or household waste. Ask your
pharmacist how to dispose of medicines no longer required. This will help protect the
environment.

6. Contents of the packaging and other information

What Irinotecan Eugia contains

• The active substance is irinotecan hydrochloride trihydrate.
• 1 mL of concentrate contains 20 mg of irinotecan hydrochloride trihydrate, equivalent to 17.33 mg of irinotecan.
• Each 2 mL vial contains 40 mg of irinotecan hydrochloride trihydrate.
• Each 5 mL vial contains 100 mg of irinotecan hydrochloride trihydrate.
• Each 15 mL vial contains 300 mg of irinotecan hydrochloride trihydrate.
• Each 25 mL vial contains 500 mg of irinotecan hydrochloride trihydrate.
• The other ingredients are sorbitol (E 420), lactic acid, sodium hydroxide, hydrochloric acid, and water for injections.

What Irinotecan Eugia looks like and contents of the pack
Concentrate for solution for infusion.
Clear, colourless to slightly yellow solution, free from visible particles.
The medicine is available in single vials containing: 40 mg/2 mL, 100 mg/5 mL, 300 mg/15 mL or 500 mg/25 mL.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Eugia Pharma (Malta) Ltd.
Vault 14, level 2
Valetta Waterfront
Floriana, FRN1914
Malta
e-mail: [email protected]

Importer:
APL Swift Services (Malta) Ltd.
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
Generis Farmacêutica, S.A.
Rua João de Deus 19, Venda Nova
2700-487 Amadora
Portugal

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Czech Republic: Irinotecan Aurovitas
Poland: Irinotecan Eugia
Portugal: Irinotecano Generis
Romania: Irinotecan Aurobindo 20 mg/ml concentrate for solution for infusion

Irinotecan Eugia, 20 mg/mL, concentrate for solution for infusion

Information intended exclusively for medical professionals:

Instructions for personnel on safe handling of the medicinal product
Irinotecan Eugia, 20 mg/mL, concentrate for solution for infusion
Like all cytotoxic medicinal products, irinotecan must be prepared and handled with caution. The use of protective goggles, mask, and gloves is required.
In case of skin contact with irinotecan, wash immediately and thoroughly with soap and water.
If irinotecan comes into contact with mucous membranes, rinse immediately and thoroughly with water.
As with all injectable medicinal products, irinotecan must be prepared under aseptic conditions.
If cloudiness or precipitation is observed in the vial or after dilution of the concentrate, the product must not be used and should be discarded according to standard procedures for cytotoxic products.

Preparation of the infusion solution
As with other injectable medicinal products, the irinotecan infusion solution must be prepared under aseptic conditions.
If precipitate is observed in the vial or in the infusion solution, the product must be discarded according to standard procedures for cytotoxic products.
Aseptically withdraw the calculated volume of irinotecan concentrate for solution for infusion from the vial into a syringe and transfer it to a 250 mL infusion bag or bottle containing 0.9% (w/v) sodium chloride solution or 5% (w/v) glucose solution for infusion. Mix the infusion solution thoroughly by gently inverting the infusion bag or bottle manually.
Do not mix with other medicinal products.

Stability period
The diluted irinotecan solution is physically and chemically stable for up to 28 days as an infusion solution (0.9% (w/v) sodium chloride solution or 5% (w/v) glucose solution) when stored in an LDPE container at 5°C or 30°C and protected from light.
When the diluted solution is not stored and protected from light, physical and chemical stability is maintained for up to 3 days.
From a microbiological standpoint, immediate use is recommended. If the product is not used immediately after dilution, the responsibility for storage duration and conditions lies with the user and should generally not exceed 24 hours at a temperature of 2°C to 8°C, unless dilution was performed under controlled aseptic conditions.

Warnings regarding visible signs of deterioration in quality
Do not use irinotecan if precipitate is observed in the vials or in the diluted solution. In such cases, the product must be discarded according to standard procedures for disposal of cytotoxic waste. Do not dispose of any medicinal products via wastewater. Consult a pharmacist on how to dispose of unused medicinal products. These measures will help protect the environment.

Administration
Information regarding administration is provided in the Summary of Product Characteristics for irinotecan.

Disposal
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.