IRINOTECAN SUN 1.5 mg/mL SOLUTION FOR INFUSION

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

Tell your doctor and DO NOT use Irinotecan SUN in any of the following cases

• if you have a chronic inflammatory bowel disease and/or intestinal obstruction
• if you are allergic to irinotecan hydrochloride trihydrate or to any of the other ingredients of this medicine (listed in section 6)
• if you are breast-feeding (see section 2)
• if you have increased bilirubin levels in the blood (more than 3 times the upper limit of normal)
• if you have severe bone marrow failure
• if your general state of health does not allow you to carry out daily activities normally (WHO performance status greater than 2)
• if you are taking or have recently taken St. John's Wort (a plant-based extract containing Hypericum).
• if you are to receive or have recently received live attenuated vaccines (vaccines against yellow fever, chickenpox, herpes zoster, measles, mumps, rubella, tuberculosis, rotavirus, flu) and for 6 months after the end of chemotherapy.

If you receive irinotecan in combination with other medicines for your disease, 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 you start using irinotecan.

• if you have Gilbert's syndrome, a hereditary disease that can cause high bilirubin levels and jaundice (yellow skin and eyes).

Since irinotecan is a cancer medicine, it will be administered in a special unit and under the supervision of a doctor experienced in the use of this type of medicine. The staff of the unit will explain what special precautions you should take during and after treatment. This package leaflet can help you remember.

Children

This medicine is only for adults. Talk to your doctor if this medicine has been prescribed for a child.

Elderly patients

Special caution is necessary in elderly patients.

Diarrhea

Irinotecan can cause diarrhea, which in some cases can be severe. This can start a few hours or a couple of days after the infusion of the medicine. 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 to get the medicine right away to have it at home when you need it.

• take the medicine as prescribed by your doctor at the first sign of loose or frequent stools
• drink plenty of water and/or electrolyte-rich beverages (carbonated water, soda, or soup)
• call your doctor or nurse if you still have diarrhea, especially if it lasts more than 24 hours, or if you are dizzy, faint, or pass out.

Neutropenia (decrease in some white blood cells)

This medicine can decrease the count of white blood cells, mainly in the weeks following the administration of the medicine. This can increase the risk of infection. Make sure to inform your doctor or nurse immediately if you have any signs of infection, such as fever (38°C or higher), chills, pain when urinating, new cough, or sputum. Avoid being near people who are sick or have infections. Inform your doctor immediately if you show signs of infection.

Blood tests

It is likely that your doctor will have blood tests done before and during treatment to monitor the effects of the medicine on your blood count or blood chemistry. Based on the results of the analysis, you may need medicines to help treat the effects. Your doctor may also reduce or delay your next dose of this medicine, or even stop it altogether. Keep all your doctor's appointments and laboratory tests.

This medicine can reduce the count of platelets in the weeks following the administration, which can increase the risk of bleeding. Talk to your doctor before taking any medicine or supplement that can affect your body's ability to stop bleeding, such as aspirin or medicines containing 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.

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 medicines before your treatment to help prevent nausea and vomiting. It is likely that your doctor will prescribe anti-nausea medicines for you to take at home. Have these medicines on hand for when you need them. Call your doctor if you cannot take fluids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

This medicine can affect the part of your nervous system that controls body secretions, leading to the so-called cholinergic syndrome. Symptoms can include runny nose, increased saliva, excessive tears in the eyes, 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.

Lung disorders

In rare cases, people taking this medicine have severe lung problems. Inform your doctor immediately if you develop a cough or if it worsens, difficulty breathing, and fever. Your doctor may need to stop your treatment to treat this problem. This medicine can increase the risk of serious blood clots in the veins of the legs or lungs, which can move 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

Contact your doctor if you have abdominal pain and constipation, especially if you also have bloating and loss of appetite.

Radiation therapy

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

Kidney function

There have been reports of kidney dysfunction.

Heart disorders

Tell your doctor if you have or have had heart disease or if you have previously received cancer medicines. Your doctor will monitor you closely and discuss how to reduce risk factors (such as smoking, high blood pressure, and high fat content).

Vascular disorders

Irinotecan is rarely associated with circulation disorders (blood clots in the legs and lungs) and can occur rarely in patients with multiple risk factors.

Others

This medicine can cause mouth sores or lip sores, often in 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 pain medicines.

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

Tell your doctor or dentist that you are being treated with this medicine if you plan to undergo surgery or any procedure.

If you are using this medicine in combination with other cancer medicines for your disease, make sure to also read the package leaflet of the other medicines.

Using Irinotecan SUN with other medicines

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

Irinotecan SUN can interact with several medicines and supplements, which can increase or decrease the level of the medicine in your blood.

Tell your doctor or pharmacist if you are using, have recently used, or could use any of the following:

• 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 plant-based 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, and idelalisib, and apalutamide)
• vitamin K antagonists (an anticoagulant used to thin the blood, such as warfarin)
• medicines used to relax muscles during general anesthesia and surgery (suxamethonium)
• 5-Fluorouracil/folinic acid
• bevacizumab (a vascular endothelial growth factor inhibitor)
• cetuximab (an epidermal growth factor receptor inhibitor).

Tell your doctor, pharmacist, or nurse before you are given Irinotecan SUN if you are already receiving or have recently received chemotherapy (and radiation therapy).

While you are being treated with irinotecan, do not start or stop taking any medicine without talking to your doctor first.

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

There may be more medicines that interact with irinotecan.

Talk to your doctor, pharmacist, or nurse about the use of other medicines, plant-based products, and supplements, and whether alcohol can cause problems with this medicine.

Contraception pregnancy, breast-feeding, and fertility

Contraception

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

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

Pregnancy

This medicine can cause harm to the fetus if used at the time of conception or during pregnancy. Before starting treatment, your doctor will make sure you are not pregnant. Men and women using this medicine must use reliable contraceptive methods during treatment. It is important to consult with your doctor what types of contraceptives can be used with this medicine. In pregnant women, treatment with this medicine should only be used if the potential benefit to the mother outweighs the risk to the fetus.

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 measured in breast milk. Breast-feeding should be discontinued during treatment with this medicine.

If you are breast-feeding, consult your doctor or pharmacist before using this medicine.

Fertility

No studies have been conducted; however, this medicine may affect fertility. Talk to your doctor about the possible risk with this medicine and the options that can preserve your ability to have children.

Driving and using machines

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

In the first 24 hours after the administration of irinotecan, you may feel dizzy or have changes in vision. If this happens, do not drive or operate machinery until it is resolved.

Irinotecan SUN contains sorbitol

This medicine contains sugar (sorbitol).

This medicine contains 607.50 mg of sorbitol in each 180 ml infusion bag, which is equivalent to 3.375 mg/ml.

This medicine contains 675.00 mg of sorbitol in each 200 ml infusion bag, which is equivalent to 3.375 mg/ml.

This medicine contains 742.50 mg of sorbitol in each 220 ml infusion bag, which is equivalent to 3.375 mg/ml.

This medicine contains 810.00 mg of sorbitol in each 240 ml infusion bag, which is equivalent to 3.375 mg/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 dizziness, vomiting, or effects such as bloating, stomach cramps, or diarrhea.

Irinotecan SUN contains sodium

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

Irinotecan SUN contains glucose

This medicine contains glucose. Patients with diabetes mellitus should note that this medicine contains 8.325 g of glucose per 180 ml infusion bag; 9.250 g of glucose per 200 ml infusion bag; 10.175 g of glucose per 220 ml infusion bag; and 11.100 g of glucose per 240 ml infusion bag.

If your doctor has told you that you have an intolerance to some sugars, consult with them before taking this medicine.

3. How to use Irinotecan SUN

If you are prescribed irinotecan, it will only be administered by doctors or nurses experienced in the administration of chemotherapy.

Method of administration

Irinotecan is administered as a solution for infusion (drip) into the veins over a period of 30 to 90 minutes.

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

Tell your caregivers if you feel burning, pain, or swelling around the needle when irinotecan is administered. If the medicine leaks out of the vein, it can cause tissue damage. If you feel pain or notice redness or swelling at the injection site while receiving irinotecan, inform the healthcare professional immediately.

Dosage of irinotecan

The dose will depend on several factors, including the treatment schedule, your body size, age, and general health, your blood counts, liver function, whether you have received radiation to the abdomen or pelvis, and whether you have any side effects, such as diarrhea. Your doctor will calculate your body surface area in square meters (m2).

If you receive irinotecan in combination with cetuximab, you should not receive irinotecan until at least 1 hour after the end of the cetuximab infusion.

Only your doctor can determine the duration of treatment.

The number of infusions you receive will depend on how you respond to treatment. Your doctor will explain this to you.

If you receive more Irinotecan SUN than you should

Seek emergency medical attention if you think you have received too much irinotecan. Overdose worsens side effects such as diarrhea or neutropenia (a decrease in the number of white blood cells in the blood). If this happens, you will receive treatment to prevent dehydration. Your white blood cell count will be monitored, and any infection will be treated as necessary.

If you miss a dose of Irinotecan SUN

Consult your doctor for instructions if you miss a scheduled infusion of irinotecan.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Your doctor will discuss these adverse effects and explain the risks and benefits of your treatment.

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

Seek emergency medical attention if you have any of these symptoms of an allergic reaction: hives; difficulty breathing; swelling of the face, lips, tongue, or throat.

• Diarrhea (see section 2).
• Early diarrhea: starts 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 can occur while the medicine is being administered. In this case, notify the healthcare professional immediately. Medicines can be administered to stop and/or reduce this early adverse effect).
• Late diarrhea: starts more than 24 hours after receiving this medicine. Due to dehydration and electrolyte imbalance problems with diarrhea, it is essential to be in contact with healthcare professionals for control and to obtain recommendations on medications and dietary modifications.

Inform your doctor or nurse if you experience any of the following symptoms.

• Very frequent: may affect more than 1 in 10 people.

† Frequent: may affect up to 1 in 10 people.

Unknown frequency (cannot be estimated from available data)

• Severe, persistent, and 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 paleness (a condition called hypovolemia)
• Allergic reaction
• Transient speech disorders during or shortly after treatment
• Numbness
• High blood pressure (during or after infusion)
• Heart problems*
• Lung disease that causes wheezing and difficulty breathing (see section 2)
• Hypo
• Intestinal obstruction
• Colon enlargement
• Intestinal bleeding
• Inflammation of the large intestine
• Abnormal laboratory test results
• Intestinal perforation
• Fatty liver
• Skin reactions
• Reactions at the site of administration
• Low potassium levels in the blood
• Low salt levels in the blood, mainly related to diarrhea and vomiting
• Muscle cramps
• Kidney problems*
• Low blood pressure*
• Fungal infections
• Viral infections.

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

If you receive Irinotecan SUN in combination with cetuximab, some of the possible adverse effects may be related to this combination. These adverse effects may include acne-like rashes. For this reason, make sure to also read the cetuximab package insert.

If you receive Irinotecan SUN in combination with capecitabine, some of the possible adverse effects may be related to this combination. These adverse effects may include very frequent blood clots, frequent allergic reactions, heart attack, and fever in patients with a low white blood cell count. For this reason, make sure to also read the capecitabine package insert.

If you receive Irinotecan SUN in combination with capecitabine and bevacizumab, some of the possible adverse effects may be related to this combination. These adverse effects may include low white blood cell count, blood clots, high blood pressure, and heart attack. For this reason, make sure to also read the capecitabine and bevacizumab package inserts.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this package insert. You can also report them directly through the Spanish Medicines and Health Products Agency's website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Irinotecan SUN

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

Do not use this medicine after the expiration date that appears on the infusion bag and on the packaging after CAD. The expiration date is the last day of the month indicated.

Store below 25°C. Store in the original packaging to protect it from light.

Once opened, the infusion bag must be used immediately.

Medicines should not be thrown away through the drains or into the trash. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Irinotecan SUN

• The active ingredient is irinotecan (as hydrochloride, trihydrate).
• The other ingredients are: glucose (E620), sorbitol (E420), (S-)lactic acid (E270), sodium hydroxide (for pH adjustment) (E524), hydrochloric acid, concentrated (for pH adjustment) (E507), and water.

A 180 ml infusion bag contains 270 mg of irinotecan hydrochloride trihydrate (which corresponds to 234 mg of irinotecan).

A 200 ml infusion bag contains 300 mg of irinotecan hydrochloride trihydrate (which corresponds to 260 mg of irinotecan).

A 220 ml infusion bag contains 330 mg of irinotecan hydrochloride trihydrate (which corresponds to 286 mg of irinotecan).

A 240 ml infusion bag contains 360 mg of irinotecan hydrochloride trihydrate (which corresponds to 312 mg of irinotecan).

1 ml of the infusion solution contains 1.5 mg of irinotecan hydrochloride trihydrate (which corresponds to 1.3 mg/ml of irinotecan).

Appearance of the product and package contents

Irinotecan SUN infusion solution is a clear, pale yellow to yellow solution, sterile, and free of visible particles.

Irinotecan SUN infusion solution is presented in packaging, each containing 1, 5, or 10 single-dose infusion bags of 180 ml, 200 ml, 220 ml, or 240 ml.

Only some package sizes may be marketed.

Marketing authorization holder

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

or

Terapia S.A.

124 Fabricii Street

400632, Cluj-Napoca

Romania

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 Barcelona

Spain

Tel.: +34 93 342 78 90

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Germany: Irinotecan SUN

Denmark: Irinotecan SUN

Spain: Irinotecán SUN

Finland: Irinotecan SUN

France: Irinotecan SUN

Italy: Irinotecan SUN

Romania: Irinotecan SUN

Sweden: Irinotecan SUN

United Kingdom (Northern Ireland): Irinotecan

Date of the last revision of this package insert:May 2024

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

This information is intended only for healthcare professionals:

Handling

• calculate the dose and decide which size of Irinotecan SUN infusion bag is needed
• inspect the product packaging for any damage. Do not use it if there are signs of tampering
• place the patient-specific label on the packaging

Removal of the infusion bag from the packaging and inspection of the infusion bag

• tear the wrapping at the notch. Do not use the medicine if the wrapping is open or damaged
• remove the infusion bag from the packaging
• use it only if the infusion bag and the seal are intact. Before administration, check for small leaks by squeezing the bag firmly. If leaks are detected, discard the bag and the solution, as it may not be sterile
• it is necessary to visually inspect parenteral medicines for any particles or discoloration before administration. If you notice the presence of particles or discoloration, do not administer it

Administration

• break the seal of the stopper by applying pressure to one side with your hand
• connect, using aseptic technique, the sterile administration equipment
• consult the instructions for use that come with the administration equipment

Precautions

• do not use in a series connection
• do not add additives to the infusion bag
• the infusion solution is ready to use and should not be mixed with other medicines
• Irinotecan SUN infusion solution is for single use only.

Adequate handling material should be provided to personnel, such as long-sleeved gowns, protective masks, caps, safety glasses, single-use sterile gloves, protective covers for the work area, and waste collection bags.

Pregnant women should not handle cytotoxic preparations.

If the product comes into contact with the eyes, it can cause intense irritation. In this case, rinse your eyes immediately with plenty of water. Consult a doctor if the irritation persists. If the solution comes into contact with the skin, rinse the affected area with plenty of water. Excreta and vomit should be handled with caution.

Elimination

The elimination of unused medicine and materials that have come into contact with it will be carried out in accordance with local regulations on cytotoxic medicines.