Irinotecan Aurovitas 20 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Irinotecan Aurovitas 20 mg/ml concentrate for solution for infusion

Irinotecan hydrochloride trihydrate

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

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

Irinotecan Aurovitas is an anticancer medicine that contains the active substance irinotecan hydrochloride trihydrate.

Irinotecan interferes with the growth and spread of cancer cells in the body.

Irinotecan is indicated alone or in combination with other anticancer medicines for the treatment of patients with advanced or metastatic colon or rectal cancer.

Irinotecan may be used as monotherapy in patients with metastatic colon or rectal cancer whose disease has recurred or worsened after initial treatment with fluorouracil.

2. What you need to know before using Irinotecan Aurovitas

Do not use Irinotecan Aurovitas

• 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 or intestinal obstruction.
• If you are breastfeeding (see section 2).
• If your bilirubin level is more than 3 times the upper limit of the normal range.
• If you have severe bone marrow failure.
• If your general health 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 scheduled to receive 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 receive 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 Aurovitas.

Exercise 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 anticancer chemotherapy.

Diarrhea

Irinotecan may cause diarrhea, which in some cases can be severe. This may begin a few hours or a few days after the infusion of the medicine. If not treated, it can 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 exactly as instructed by your doctor at the first sign of loose or frequent stools.
• Drink plenty of water and/or electrolyte-containing beverages (sparkling water, soda, or soup).
• Contact 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 (reduction in certain white blood cells)

This medicine may decrease white blood cell counts, primarily in the weeks following administration. This may increase the risk of developing infections. Inform your doctor or nurse immediately if you experience any signs of infection, such as fever (38°C or higher), chills, painful urination, new cough, or sputum. Avoid contact with people who are ill or have infections. Inform your doctor immediately if you develop signs of infection.

Blood monitoring

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 test results, you may require additional medicines to manage side 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 acetylsalicylic acid or medicines containing acetylsalicylic acid, warfarin, or vitamin E. Inform your doctor immediately if you develop unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing teeth, or black, tarry stools.

Nausea 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 will likely prescribe anti-nausea medicines for you to take at home. Keep these medicines available for when you need them. Contact your doctor if you are unable to take fluids orally due to nausea and vomiting.

Acute cholinergic syndrome

This medicine may affect the part of your nervous system that controls bodily 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 experience any of these symptoms, as medicines are available to help control them.

Lung disorders

Rarely, people taking this medicine may develop serious lung problems. Inform your doctor immediately if you develop cough or worsening cough, difficulty breathing, or fever. Your doctor may need to discontinue treatment to manage this condition.

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 intestinal inflammation and/or intestinal obstruction

Contact your doctor if you have abdominal pain and constipation, especially if accompanied by 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 treatment with irinotecan.

Kidney function

Cases of renal dysfunction have been reported.

Heart disorders

Inform your doctor if you have or have had heart disease or if you previously received cancer medicines. Your doctor will monitor you closely and discuss how risk factors (e.g., smoking, high blood pressure, high fat levels) can be reduced.

Vascular disorders

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

If you have Gilbert’s syndrome, a hereditary disorder that may cause high bilirubin levels and jaundice (yellowing of the skin and eyes).

Other

This medicine may cause mouth or lip ulcers, often in the first few weeks after starting treatment. This may lead to mouth pain, bleeding, or difficulty eating. Your doctor or nurse may suggest ways to reduce this, such as changing how you eat or brush your teeth. If needed, your doctor may prescribe pain medication.

For information on contraception, pregnancy, breastfeeding, and fertility, 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 medicines for 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 Aurovitas

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Irinotecan may interact with various medicines and supplements, which may increase or decrease the level of the medicine in your blood. Inform your doctor or pharmacist if you are taking or have taken any of the following medicines:

• Medicines used to treat epilepsy (carbamazepine, phenobarbital, phenytoin, and fosphenytoin).
• Medicines used to treat fungal infections (ketoconazole, itraconazole, voriconazole, and posaconazole).
• Medicines used to treat bacterial infections (clarithromycin, erythromycin, and telithromycin).
• 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 immune system to prevent transplant rejection (cyclosporine and tacrolimus).
• Medicines used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamide).
• Vitamin K antagonists (common anticoagulants such as warfarin).
• Medicines used to relax muscles during general anesthesia and surgery (suxamethonium).
• 5-Fluorouracil/folinic acid.
• Bevacizumab (a blood vessel growth inhibitor).
• Cetuximab (an epidermal growth factor receptor inhibitor).

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

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 taking 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 an effective method of contraception during treatment and for at least 6 months after completing treatment.

If you are a man, you must use an effective method of contraception during treatment and for at least 3 months after completing treatment. 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 risks and options that may preserve your ability to have children.

Driving and use of machines

For approximately the first 24 hours after receiving irinotecan, you may experience dizziness or visual disturbances. If you experience these symptoms, do not drive or operate machinery.

Irinotecan Aurovitas contains sorbitol

This medicine contains sorbitol. 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 administered. Patients with HFI cannot metabolize 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 unpleasant effects such as bloating, stomach cramps, or diarrhea.

Irinotecan Aurovitas contains sodium

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

3. How to use Irinotecan Aurovitas

Follow exactly the instructions for administration of this medicine as 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 of 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). You will receive this injection at a clinic or hospital. Irinotecan must be administered slowly, and the intravenous infusion may take up to 90 minutes to complete.

You may be given other medications to prevent nausea, vomiting, diarrhea, and other side effects while you receive irinotecan. You may need to continue taking these medications for at least one day after your irinotecan injection.

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 experience pain or notice redness or swelling at the injection site while receiving irinotecan, inform the healthcare professional immediately.

Several treatment schedules are currently recommended for irinotecan. It is usually administered once every 3 weeks (irinotecan given alone) or once every 2 weeks (irinotecan given in combination with 5FU/FA chemotherapy). The dose will depend on several factors, including the treatment schedule, your body size, age and general health, 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 Aurovitas than you should

Seek urgent medical attention. Symptoms of overdose may include some of the serious side effects listed in this leaflet.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately, or call the Toxicology Information Service at 91 562 04 20, stating the medicine and the amount administered.

If you forget to use Irinotecan Aurovitas

Consult your doctor for instructions if you miss an appointment for your irinotecan injection.

Do not use a double dose to make up for missed doses.

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 may cause adverse effects, although not everybody gets 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 urgent medical attention if you have any of these 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, abdominal cramps (this may occur during administration of the medicine. In this case, notify the healthcare professional promptly. Medicines may 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 modifications.

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 weak and lacking energy	Very common	Very common
Low platelet count (blood cells that help 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 kidney 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 the available data)

• Severe, persistent, 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.

• Elevated blood pressure (during or after infusion).

• Heart problems*.

• Lung disease causing wheezing and difficulty breathing (see section 2).

• Hiccups.

• Intestinal obstruction.

• Enlargement of the colon.

• Intestinal bleeding.

• Inflammation of the large intestine.

• Abnormal laboratory test results.

• Intestinal perforation.

• Fatty liver.

• Skin reactions.

• Reactions at the site of administration.

• Low potassium levels in the blood.

• Low levels of salts in the blood, mainly related to diarrhoea and vomiting.

• Muscle cramps.

• Kidney problems*.

• Low blood pressure.

• Fungal infections.

• Viral infections.

• These events have been observed infrequently in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or blood infections.

Reporting of adverse reactions

If you experience any kind 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 Aurovitas

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

Do not freeze.

For single use only.

Keep the vial in the outer packaging to protect it from light.

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

The product should be diluted and used immediately after opening.

If prepared under aseptic conditions, the diluted solution may be stored for 24 hours at temperatures below 30°C and for 48 hours between 2–8°C (i.e. in a refrigerator).

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

6. Contents of the pack and other information

Composition of Irinotecan Aurovitas

• 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.
• A 2 ml vial contains 40 mg of irinotecan hydrochloride trihydrate.
• A 5 ml vial contains 100 mg of irinotecan hydrochloride trihydrate.
• A 15 ml vial contains 300 mg of irinotecan hydrochloride trihydrate.
• A 25 ml vial contains 500 mg of irinotecan hydrochloride trihydrate.
• The other components are: sorbitol E420, lactic acid, sodium hydroxide, hydrochloric acid and water for injections.

Appearance of the product and contents of the pack

Irinotecan Aurovitas 20 mg/ml concentrate for solution for infusion is a clear, colourless or slightly yellow solution.

Pack sizes:

1 vial of 2 ml

1 vial of 5 ml

5 vials of 5 ml

1 vial of 15 ml

1 vial of 25 ml

Only some pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront
Floriana, FRN 1914
Malta

Manufacturer

Generis Farmacêutica, S.A.
Rua João de Deus, nº 19, Venda Nova
2700-487 Amadora
Portugal

Or

APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Aurovitas Spain, S.A.U.
Avda. de Burgos, 16-D
28036 Madrid
Spain

This medicinal product is authorised in the European Economic Area member states under the following names:

Germany: Irinotecan Aurobindo 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Belgium: Irinotecan AB 20 mg/ml concentraat voor oplossing voor infusie

Spain: Irinotecán Aurovitas 20 mg/ml concentrado para solución para perfusión

France: IRINOTECAN ARROW 20 mg/ml, solution à diluer pour perfusion

Italy: Irinotican Aurobindo

Netherlands: Irinotecan Aurobindo 20 mg/ml, concentraat voor oplossing voor infusie

Portugal: Irinotecano Aurovitas

Date of the latest revision of this leaflet: April 2022

Other sources of information

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

This information is intended for healthcare professionals only:

Instructions for use

Cytotoxic

Handling of Irinotecan Aurovitas

Like other antineoplastic agents, irinotecan must be prepared and handled with care. Dilution must be carried out under aseptic conditions by experienced personnel in a designated area. Precautions should be taken to avoid contact with skin and mucous membranes.

Safety instructions for the preparation of irinotecan solution for infusion:

1. A safety cabinet, protective gloves and gown must be used. If a safety cabinet is not available, protective goggles and a mask must be worn.
2. Opened containers such as vials, infusion bottles, cannulae, syringes, catheters, tubing used, and cytostatic waste must be considered hazardous waste and must be disposed of in accordance with local regulations for handling HAZARDOUS WASTE.
3. In case of spillage, follow these instructions:
   • Wear protective clothing.
   • Collect broken glass and dispose of it in a HAZARDOUS WASTE container.
   • Rinse contaminated surfaces thoroughly with copious amounts of cold water.
   • Clean rinsed surfaces carefully, and dispose of all materials used as HAZARDOUS WASTE.
4. If Irinotecan Aurovitas comes into contact with the skin, rinse the affected area with plenty of running water and then wash with water and soap. In case of contact with mucous membranes, thoroughly rinse the affected area with water. If any discomfort is experienced, contact a physician.
5. If Irinotecan Aurovitas comes into contact with the eyes, rinse them thoroughly with copious amounts of water. Contact an ophthalmologist immediately.

Preparation of the infusion solution

Irinotecan Aurovitas concentrate for solution for infusion is intended for intravenous infusion after dilution in the recommended diluents: 0.9% sodium chloride solution for infusion or 5% glucose solution for infusion. Under aseptic conditions, withdraw the required amount of Irinotecan Aurovitas concentrate for solution using a graduated syringe from the vial and inject it into a 250 ml infusion bag or bottle. The infusion solution should be mixed carefully by manual rotation.

If any precipitate is observed in the vials or after dilution, the product must be discarded according to standard procedures for disposal of cytotoxic agents.

Irinotecan must be administered as an intravenous bolus or intravenous infusion lasting not less than 30 minutes and not more than 90 minutes.

Disposal

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