Irinotecan Sun

1. What is Irinotecan and what is it used for

Irinotecan is an anticancer medicine that contains irinotecan hydrochloride trihydrate as the active substance.
Irinotecan hydrochloride trihydrate disrupts the growth and spread of cancer cells in the body.
Irinotecan is indicated in combination with other medicines used to treat patients with advanced or metastatic colorectal cancer.
Irinotecan can be used alone in patients with metastatic colorectal cancer who have had a relapse or progression of the disease after initial fluorouracil therapy.

2. Important information before using Irinotecan

Do not use Irinotecan if any of the following situations apply to the patient.

Inform your doctor if:

• the patient has chronic inflammatory bowel disease and/or bowel obstruction
• the patient is allergic to irinotecan hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6)
• the patient is breastfeeding
• the patient has a high bilirubin level in the blood (more than three times the upper limit of normal)
• the patient has severe bone marrow disorders
• the patient's general health does not allow them to perform daily activities (WHO performance status greater than 2)

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• the patient is taking or has recently taken St. John's wort (herbal dietary supplements containing St. John's wort)
• the patient intends to use or has recently used live, attenuated microorganism vaccines (vaccines against yellow fever, chickenpox, whooping cough, measles, mumps, rubella, tuberculosis, rotavirus infections, influenza) and within 6 months after the end of chemotherapy.

In case of using Irinotecan in combination with other medicines, you should also read the patient information leaflet attached to the other medicines to get information about additional contraindications.

Warnings and precautions

Before starting treatment with Irinotecan, discuss it with your doctor, pharmacist, or nurse:

• if the patient has Gilbert's syndrome, a hereditary disease that may cause elevated bilirubin levels and jaundice (yellowing of the skin and eyes).

Irinotecan is an anticancer medicine and will be administered to the patient in a specialized center and under the supervision of a doctor qualified in the administration of anticancer medicines. The center's staff will explain to the patient what to pay special attention to during and after treatment. This leaflet can help the patient remember this information.

Children

This medicine is intended only for adult patients. If the medicine has been prescribed for use in a child, consult a doctor.

Elderly patients

Caution should be exercised in elderly patients.
Diarrhea
Irinotecan may cause diarrhea, which can be severe in some cases.
Diarrhea may start a few hours or a few days after infusion. If left untreated, it may lead to dehydration and severe electrolyte disturbances, which can be life-threatening.
The doctor will prescribe medicines to help prevent or control these side effects. Make sure the medicine is available at home in case it is needed:

• the medicine should be taken as directed by the doctor after the first appearance of loose or frequent stools
• drink plenty of water and/or salty fluids (carbonated water, soda, or soup)
• contact the doctor or nurse if diarrhea persists, especially if it lasts longer than 24 hours or if there is a feeling of emptiness in the head, dizziness, or fainting.

Neutropenia (decrease in the number of a certain type of white blood cell)
The medicine may lower the number of white blood cells, especially in the first few weeks after administration.
This may increase the risk of infection. Inform the doctor or nurse immediately if any signs of infection occur, such as fever (38°C or higher), chills, pain when urinating, coughing, or expectoration of sputum. Avoid being near people who are sick or have an infection. Inform the doctor immediately if signs of infection occur.
Blood monitoring
It is likely that before starting treatment and during treatment, the doctor will perform blood tests to check the effect of the medicine on blood cell count or blood composition. The test results may show the need to use medicines that help treat these reactions. The doctor may also be forced to reduce or delay the next dose of the medicine, or even stop treatment. Attend all scheduled doctor's appointments and laboratory tests.
The medicine may decrease the number of platelets in the blood within a few weeks after administration, which may increase the risk of bleeding. Consult a doctor before taking any medicines or supplements that may affect bleeding, such as aspirin or medicines containing aspirin, warfarin, or vitamin E. Inform the doctor immediately if unusual bruising or bleeding occurs, such as nosebleeds, bleeding gums when brushing teeth, or black, tarry stools.
Nausea and vomiting
Nausea and vomiting may occur on the day of administration or within a few days after administration. Before starting treatment, the doctor may administer a medicine to prevent nausea and vomiting. The doctor will likely prescribe anti-emetic medicines that can be taken at home. These medicines should be readily available in case they are needed. Contact the doctor if nausea and vomiting prevent the patient from taking fluids by mouth.
Acute cholinergic syndrome
The medicine may affect the part of the nervous system that controls secretory functions, leading to a so-called cholinergic syndrome. Symptoms may include runny nose, increased salivation, excessive tearing, sweating, flushing, abdominal cramps, and diarrhea. Inform the doctor or nurse if any of these symptoms are noticed, as there are medicines that can help control them.
Respiratory disorders
In patients taking this medicine, serious lung problems have been observed in rare cases. Inform the doctor immediately if coughing, difficulty breathing, or fever occur. To address these problems, the doctor may be forced to interrupt treatment.
The medicine may increase the risk of large blood clots in the veins of the legs or lungs, which can travel to other parts of the body, such as the lungs or brain. Inform the doctor immediately if the patient experiences chest pain, shortness of breath, or swelling, pain, redness, or a feeling of warmth in the arm or leg.
Chronic intestinal inflammation and/or bowel obstruction
Inform the doctor if the patient experiences abdominal pain and cannot have a bowel movement, especially if there is also bloating and loss of appetite.
Radiation therapy
If the patient has recently undergone radiation therapy to the pelvis or abdomen, there may be an increased risk of bone marrow suppression. Consult a doctor before starting Irinotecan treatment.
Kidney function
Reports of kidney function disorders have been made.
Heart disorders
Inform the doctor if the patient has or has had heart disease or has previously received anticancer medicines. The doctor will closely monitor the patient and

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discuss with them how to reduce risk factors (such as smoking, high blood pressure, and high fat content in the diet).
Vascular disorders
Using Irinotecan has been associated with vascular disorders (blood clots in the veins of the legs and lungs) in rare cases; these can occur rarely in patients with multiple risk factors.
Other
The medicine may cause mouth ulcers or sores on the lips, often within the first few weeks after starting treatment. This can cause pain in the mouth, bleeding, and even problems with eating. The doctor or nurse may suggest ways to reduce these discomforts, such as changing the way of eating or brushing teeth. If necessary, the doctor may prescribe a medicine to reduce pain.
In case of planned surgery or other procedures, inform the doctor or dentist about the use of this medicine.
If the medicine is used in combination with other anticancer medicines, also read the patient information leaflet attached to the other anticancer medicine.

Irinotecan and other medicines

Tell your doctor or pharmacist about all medicines the patient is taking or has recently taken, as well as any medicines the patient plans to take, including those that are available without a prescription.
Irinotecan may interact with many other medicines and supplements, which may increase or decrease the level of this medicine in the blood.

Inform your doctor if the patient is taking

• medicines used to treat seizures (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 (herbal dietary supplement)
• live, attenuated microorganisms as vaccines
• medicines used to treat HIV infection (indinavir, ritonavir, amprenavir, fosamprenavir, nelfinavir, atazanavir, and others)
• medicines that suppress the immune system, used to prevent transplant rejection (cyclosporine or tacrolimus)
• medicines used to treat cancer (regorafenib, crizotinib, idelalisib, and apalutamide)
• vitamin K antagonists (blood thinners, such as warfarin)
• medicines used to relax muscles during general anesthesia and surgery (suxamethonium)
• 5-fluorouracil/folinic acid
• bevacizumab (vascular endothelial growth factor inhibitor)
• cetuximab (epidermal growth factor receptor inhibitor).

Before administering Irinotecan, tell your doctor, pharmacist, or nurse if the patient is currently or has recently undergone chemotherapy (and radiation therapy).
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Do not start or stop taking any medicines during Irinotecan treatment without consulting a doctor first.
This medicine may cause severe diarrhea. While taking this medicine, do not take laxatives or stool softeners.
It is possible that other medicines may also interact with Irinotecan. Consult a doctor, pharmacist, or nurse to check if other medicines, herbal preparations, and supplements, as well as alcohol, may interact with this medicine.

Pregnancy, breastfeeding, and fertility

Women of childbearing age and men must use effective contraception during treatment and for up to 1 month and 3 months after its completion, respectively.
Pregnancy
If used during conception or during pregnancy, this medicine may harm the fetus. Men and women taking this medicine should use effective contraception during treatment. It is essential to consult a doctor about what contraceptive methods can be used. In pregnant women, treatment with this medicine should only be used when the potential benefits to the mother outweigh the risk to the fetus.
If the patient is pregnant, thinks they may be pregnant, or plans to have a child, they should consult a doctor or pharmacist before using this medicine.
Breastfeeding
No studies have been conducted on breastfeeding, however, this medicine passes into breast milk and may affect the baby.
Breastfeeding should be stopped during treatment with this medicine.
If the patient is breastfeeding, they should consult a doctor or pharmacist before using this medicine.
Fertility
No studies have been conducted on fertility, however, this medicine may affect fertility. Consult a doctor about the possible risk associated with using this medicine and the possibility of protecting the patient so that they can have children in the future.

Driving and using machines

In some cases, Irinotecan may cause side effects that can affect the ability to drive and use machines. In case of doubt, consult a doctor or pharmacist.
Within 24 hours after administration of Irinotecan, dizziness or vision problems may occur. If such side effects occur, do not drive or operate machines until they have resolved.

Irinotecan SUN contains sorbitol

Sorbitol is a source of fructose.
If the patient has been previously diagnosed with hereditary fructose intolerance, a rare genetic disease, they must not take this medicine. In patients with hereditary fructose intolerance, the body does not break down the fructose contained in this medicine, which can cause severe side effects.
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If the patient has hereditary fructose intolerance, they must inform their doctor before starting treatment.

Irinotecan contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means the medicine is essentially 'sodium-free'.

3. How to use Irinotecan

If Irinotecan has been prescribed for the patient, the medicine will be administered only by doctors or nurses experienced in chemotherapy.

Method of administration

Irinotecan is administered by intravenous infusion (drip) lasting from 30 to 90 minutes.
During Irinotecan administration, the patient may also receive other medicines intended to prevent nausea, vomiting, diarrhea, and other side effects.
Taking these medicines may be required for at least one day after the Irinotecan infusion.
Inform the people taking care of the patient about any burning, pain, or swelling around the infusion site during Irinotecan administration.
Leakage of the medicine outside the vein can cause tissue damage. If pain, redness, or swelling occurs around the infusion site during Irinotecan administration, immediately inform the medical staff.

What is the dose of Irinotecan

The dose depends on several factors, including the treatment schedule, body size, age, and overall health, blood count results, liver function, radiation therapy to the abdominal/pelvic area, and the presence of side effects, such as diarrhea. The doctor will calculate the body surface area in square meters (m²).

• Patient previously treated with 5-fluorouracil will usually receive Irinotecan as monotherapy, starting with a dose of 350 mg/m² every three weeks.
• Patient not previously treated with chemotherapy will usually receive Irinotecan at a dose of 180 mg/m² every two weeks, followed by folinic acid and 5-fluorouracil.

In patients receiving Irinotecan in combination with cetuximab, Irinotecan should not be administered until at least 1 hour after the end of the cetuximab infusion.
The duration of treatment will be assessed only by the treating doctor.
The number of infusions administered will depend on the patient's response to treatment. This will be discussed with the patient by the treating doctor.

What to do if a higher dose of Irinotecan is used than recommended

If the patient thinks they have received too high a dose of Irinotecan, they should seek immediate medical attention. Overdose increases the side effects, such as diarrhea or neutropenia (decrease in the number of white blood cells in the blood). In this case, the patient will receive treatment to prevent dehydration. The white blood cell count will be monitored, and any infections will be treated as necessary.

What to do if a dose of Irinotecan is missed

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If the patient misses an appointment where they were supposed to receive an Irinotecan infusion, they should contact their doctor for instructions.
In case of any further doubts about using this medicine, consult a doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Irinotecan can cause side effects, although not everybody gets them.
The doctor will discuss these side effects with the patient and explain the risks and benefits of treatment.
Some side effects can be serious. Contact a doctor immediately if any of the following serious side effects occur (see section 2).
Seek medical help immediately if any symptoms of an allergic reaction occur: hives; difficulty breathing; swelling of the face, lips, tongue, or throat.

• diarrhea (see section 2).
• early diarrhea: occurs within 24 hours after administration, with symptoms of runny nose, increased salivation, tearing, sweating, flushing, abdominal cramps. (This reaction may occur during administration. In this case, immediately inform the medical staff. Medicines can be administered to stop and/or reduce these symptoms).
• late diarrhea: occurs later than 24 hours after administration. Due to the possibility of dehydration and electrolyte disturbances caused by diarrhea, it is essential to stay in contact with healthcare professionals to monitor the patient's condition and receive recommendations for medicines and dietary changes.

If any of the following symptoms occur, inform a doctor or nurse.

Frequency of occurrence in monotherapy

Frequency of occurrence in combination therapy

Abnormally low number of white blood cells increasing the risk of infection
Very common
Very common
Very common
Very common
Low number of red blood cells causing fatigue and shortness of breath
Decreased appetite
Very common
Very common
Very common
Very common
Cholinergic syndrome (see section 2: "Warnings and precautions")
Vomiting
Very common
Very common
Nausea
Very common
Very common
Abdominal pain
Very common
Common
Hair loss (reversible)
Very common
Very common
Mucosal inflammation
Very common
Very common
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Frequency of occurrence in monotherapy

Frequency of occurrence in combination therapy

Fever
Very common
Common
Weakness and lack of energy
Very common
Very common
Low number of platelets (which are involved in the blood clotting process) causing bruising or bleeding
Common
Very common
Common
Very common
Abnormal liver function test results
Infection
Common
Common
Common
Common
Low number of white blood cells with fever
Difficulty passing stools
Common
Common
Common
Not reported
Abnormal kidney function test results

Frequency not known: frequency cannot be estimated from the available data:

• severe, persistent, or bloody diarrhea (which may be accompanied by abdominal pain or fever) caused by the bacterium Clostridium difficile
• blood infection
• dehydration (due to diarrhea and vomiting)
• dizziness, rapid heartbeat, and paleness (a condition called hypovolemia)
• allergic reaction
• temporary speech disorders during or shortly after treatment
• tingling
• high blood pressure (during or after infusion)
• heart problems*
• lung disease causing wheezing and shortness of breath (see section 2)
• hiccups
• intestinal obstruction
• enlargement of the intestine
• intestinal bleeding
• inflammation of the large intestine
• abnormal laboratory test results
• perforation of the intestine
• fatty liver
• skin reactions
• reactions at the injection site
• low potassium levels in the blood
• low salt levels in the blood, mainly associated with diarrhea and vomiting
• muscle cramps
• kidney problems*
• low blood pressure*
• fungal infections

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• viral infections.

* Rare cases of these events have been observed in patients who have had episodes of dehydration associated with diarrhea and/or vomiting or blood infections.
If the patient is receiving Irinotecan in combination with cetuximab, some of the side effects they experience may be related to the use of this combination of medicines. These may include acne-like rash. For this reason, also read the patient information leaflet for cetuximab.
If the patient is receiving Irinotecan in combination with capecitabine, some of the side effects they experience may be related to the use of this combination of medicines. These may include very common thrombosis, common allergic reactions, myocardial infarction, and fever in patients with low white blood cell count. For this reason, also read the patient information leaflet for capecitabine.
If the patient is receiving Irinotecan in combination with capecitabine and bevacizumab, some of the side effects they experience may be related to the use of this combination of medicines. These may include low white blood cell count, thrombosis, high blood pressure, and myocardial infarction. For this reason, also read the patient information leaflet for capecitabine and bevacizumab.
Reporting side effects
If side effects occur, including any side effects not listed in this leaflet, inform a doctor or pharmacist, or nurse.
Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of this medicine.

5. How to store Irinotecan

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the infusion bag and outer packaging after EXP. The expiry date refers to the last day of the month stated.
Store below 25°C. Keep in the original packaging to protect from light.
After opening the infusion bag, its contents should be used immediately.
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Medicines should not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Irinotecan contains

• The active substance is irinotecan (in the form of hydrochloride trihydrate).
• The other ingredients are: glucose (E620), sorbitol (E420), (S)-lactic acid (E270), sodium hydroxide (to adjust pH) (E524), concentrated hydrochloric acid (to adjust pH) (E507), and water.

One infusion bag with a capacity of 180 ml contains 270 mg of irinotecan hydrochloride trihydrate (equivalent to 234 mg of irinotecan).
One infusion bag with a capacity of 200 ml contains 300 mg of irinotecan hydrochloride trihydrate (equivalent to 260 mg of irinotecan).
One infusion bag with a capacity of 220 ml contains 330 mg of irinotecan hydrochloride trihydrate (equivalent to 286 mg of irinotecan).
One infusion bag with a capacity of 240 ml contains 360 mg of irinotecan hydrochloride trihydrate (equivalent to 312 mg of irinotecan).
One milliliter of the infusion solution contains 1.5 mg of irinotecan hydrochloride trihydrate (equivalent to 1.3 mg/ml of irinotecan).

What Irinotecan looks like and contents of the pack

Irinotecan infusion solution is a clear, pale yellow to yellow, sterile solution without visible particles.
Irinotecan infusion solution is supplied in cardboard boxes containing 1, 5, or 10 infusion bags for single-dose infusion with a volume of 180 ml, 200 ml, 220 ml, or 240 ml.
Not all pack sizes may be marketed.

Marketing authorization holder

Sun Pharmaceutical Industries Europe BV
Polarisavenue 87
2132 JH Hoofddorp
Netherlands

Manufacturer/Importer

Sun Pharmaceutical Industries Europe BV
Polarisavenue 87
2132 JH Hoofddorp
Netherlands
Terapia S.A.
124 Fabricii Street
400632, Cluj-Napoca
Cluj County
Romania

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

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Denmark:
Irinotecan SUN
Finland:
Irinotecan SUN
Germany:
Irinotecan SUN
Spain:
Irinotecan SUN
France:
Irinotecan SUN
Italy:
Irinotecan SUN
Romania:
Irinotecan SUN
Sweden:
Irinotecan SUN
United Kingdom (Northern Ireland): Irinotecan

For further information on this medicine, contact the representative of the marketing authorization holder:

Ranbaxy (Poland) Sp. z o.o.
ul. Kubickiego 11
02-954 Warsaw
phone: 22 642 07 75
Date of last revision of the leaflet:14.02.2022
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Information intended for healthcare professionals only:

Preparation for use

• calculate the dose and decide which size of Irinotecan SUN infusion bag is needed for the infusion
• check the product packaging for any signs of damage. Do not use if there are any visible signs of tampering
• apply a label with patient information to the protective bag.

Removing the infusion bag from the protective bag and checking the infusion bag

• tear the protective bag at the notch. Do not use if the protective bag has been previously opened or is damaged
• remove the infusion bag from the protective bag
• use only if the bag and seal are intact. Before administration, firmly squeeze the bag to check for any leaks. If a leak is detected, discard the bag and solution, as its sterility may have been compromised
• parenteral medicines should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is observed, do not administer.

Administration

• break the seal on the stopper by pressing with one hand
• while maintaining asepsis, connect a sterile administration set
• follow the instructions provided with the administration set.

Precautions

• do not use in serial connections
• do not add other medicines to the infusion bag
• the infusion solution is ready for use and should not be mixed with other medicines
• Irinotecan SUN infusion solution is for intravenous use only.

Personnel should be equipped with appropriate materials, including long-sleeved gowns, protective masks, caps, protective eyewear, sterile single-use gloves, protective covers for the work area, and waste collection bags.
Cytotoxic preparations should not be handled by pregnant women.
In case of contact of the product with the eyes, severe irritation may occur. In this case, immediately rinse the eyes thoroughly. If irritation persists, consult a doctor. In case of contact of the solution with the skin, rinse the affected area thoroughly with water. Exercise caution when handling patient excreta and vomit.
Disposal
Unused medicinal products or any materials to be disposed of should be disposed of in accordance with local procedures for the disposal of cytotoxic waste.