Irinotecan sun

DE/H/5810/1/II/004 & DE/H/5810/001/IB/005

Package leaflet: Information for the user

Irinotecan SUN, 1.5 mg/ml, concentrate for solution for infusion
irinotecan hydrochloride trihydrate
Please read all of this leaflet carefully before you are given the medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of the leaflet:

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

1. What Irinotecan is and what it is used for

Irinotecan is an anticancer medicine containing irinotecan hydrochloride trihydrate as the active substance.
Irinotecan hydrochloride trihydrate interferes with the growth and spread of cancer cells in the body.
Irinotecan is indicated in combination with other medicines for the treatment of patients with advanced or metastatic carcinoma of the colon or rectum.
Irinotecan may be used alone in patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed after initial therapy with fluorouracil.

2. Important information before using Irinotecan

DO NOT use Irinotecan if any of the following apply to the patient.
You should inform the doctor if:

• the patient has chronic inflammatory bowel disease and/or intestinal 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 high levels of bilirubin in the blood (more than three times the upper limit of normal)
• the patient has severe bone marrow dysfunction
• the patient’s general health does not allow them to perform daily activities (WHO performance status higher than 2)

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• the patient is taking or has recently taken St. John’s wort preparations (herbal extracts containing St. John’s wort)
• the patient intends to receive or has recently received vaccines containing live attenuated microorganisms (vaccines against yellow fever, varicella, shingles, measles, mumps, rubella, tuberculosis, rotavirus infections, influenza) and within 6 months after completion of chemotherapy.

When Irinotecan is used in combination with other medicines, please refer to the patient leaflets included with the other medicines for information on additional contraindications.
Warnings and precautions
Before starting treatment with Irinotecan, discuss this with the doctor, pharmacist or nurse:

• if the patient has Gilbert’s syndrome, a hereditary condition which 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 centre and under the supervision of a doctor experienced in administering anticancer medicines. The centre’s staff will explain to the patient what particular attention should be paid to during and after treatment. This leaflet may help the patient remember this information.
Children
This medicine is intended only for adult patients. If the medicine has been prescribed for a child, consult with the doctor.
Elderly patients
Particular caution should be exercised in elderly patients.
Diarrhoea
Irinotecan may cause diarrhoea, which in some cases may be severe.
Diarrhoea may begin within a few hours or several days after the infusion. If left untreated, it may lead to dehydration and severe electrolyte imbalances, which may be life-threatening.
The doctor will prescribe medicines to help prevent or control these adverse effects. Ensure that the medicine is immediately available so that the patient can take it at home if needed:

• take the medicine as directed by the doctor at the first sign of loose or frequent stools
• drink plenty of water and/or salty fluids (carbonated water, soft drinks or soup)
• contact the doctor or nurse if diarrhoea persists, especially if it lasts longer than 24 hours or if dizziness, lightheadedness or fainting occurs.

Neutropenia (reduction in the number of certain types of white blood cells)
The medicine may reduce the number of white blood cells, particularly during 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 during urination, cough or sputum production. Avoid contact with sick people or those with infections. Inform the doctor immediately if signs of infection occur.
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Blood monitoring
It is likely that the doctor will perform blood tests before starting therapy and during treatment to check the effect of the medicine on blood cell counts or blood composition. The results may indicate the need for additional medicines to help manage these reactions. The doctor may also need to reduce or delay the next dose, or even discontinue treatment. Attend all scheduled medical appointments and laboratory tests.
This medicine may reduce the number of platelets within the first few weeks after administration, increasing the risk of bleeding. Consult the doctor before taking any medicines or supplements that may affect blood clotting, such as acetylsalicylic acid or medicines containing acetylsalicylic acid, warfarin or vitamin E. Inform the doctor immediately if unusual bruising or bleeding occurs, 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 a few days after administration. Before starting treatment, the doctor may administer a medicine to prevent nausea and vomiting. The doctor will likely prescribe antiemetic medicines for the patient to take at home. These medicines should be readily available if needed. Contact the doctor if nausea and vomiting prevent the patient from taking fluids orally.
Acute cholinergic syndrome
The medicine may affect part of the nervous system that controls secretory functions, leading to so-called cholinergic syndrome. Symptoms may include runny nose, increased salivation, excessive tearing, sweating, flushing, abdominal cramps and diarrhoea. Inform the doctor or nurse if any of these symptoms occur, as there are medicines that can help control them.
Lung function disorders
Serious lung problems have been observed in rare cases in patients receiving this medicine. Inform the doctor immediately if cough, breathing difficulties or fever develop or worsen. The doctor may need to interrupt treatment to manage these problems.
This medicine may increase the risk of developing large 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 the doctor immediately if the patient experiences chest pain, shortness of breath, or swelling, pain, redness or warmth in the arm or leg.
Chronic inflammatory bowel disease and/or intestinal obstruction
Inform the doctor if the patient experiences abdominal pain and is unable to defecate, especially if accompanied by bloating and loss of appetite.
Radiation therapy
If the patient has recently undergone pelvic or abdominal radiation therapy, there may be an increased risk of bone marrow suppression. Discuss this with the doctor before starting Irinotecan treatment.
Kidney function
Kidney function disorders have been reported.
Heart disorders
Inform the doctor if the patient has or has had heart disease or previously received anticancer medicines. The doctor will closely monitor the patient and
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discuss ways to reduce risk factors (e.g. smoking, high blood pressure, high dietary fat content).
Vascular disorders
Rarely, the use of Irinotecan has been associated with blood flow disorders (blood clots in the vessels of the legs and lungs); these may rarely occur in patients with multiple risk factors.
Other
This medicine may cause mouth or lip ulcers, often within the first few weeks of starting treatment. This may cause mouth pain, bleeding, and even eating difficulties. The doctor or nurse may suggest ways to reduce these discomforts, such as changing eating or tooth brushing habits. If needed, the doctor may prescribe a medicine to reduce pain.
If planning surgery or another procedure, inform the doctor or dentist about taking this medicine.
If the medicine is used in combination with other anticancer medicines, also refer to the leaflet included with the other anticancer medicine.
Irinotecan and other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including over-the-counter medicines.
Irinotecan may interact with many other medicines and supplements, which may increase or decrease the concentration of this medicine in the blood.
Inform the 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 anaesthesia and surgery (succinylcholine)
• 5-fluorouracil/folinic acid
• bevacizumab (blood vessel growth inhibitor)
• cetuximab (EGFR inhibitor).

Before receiving Irinotecan, inform the 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 treatment with Irinotecan without first consulting the doctor.
This medicine may cause severe diarrhoea. While taking this medicine, do not take laxatives or stool softeners.
Other medicines may also interact with Irinotecan. Consult the doctor, pharmacist or nurse to check whether other medicines, herbal preparations, supplements or alcohol may interact with this medicine.
Pregnancy, breastfeeding and effects on fertility
Women of childbearing potential and men must use effective contraception during treatment and for an appropriate period of 1 month and 3 months after completion of treatment, respectively.
Pregnancy
If used at conception or during pregnancy, this medicine may harm the unborn child. Men and women taking this medicine should use effective contraception during treatment. It is important to consult the doctor about which type of contraceptive method may be used. In pregnant women, treatment with this medicine should only be used if the potential benefit to the mother outweighs the risk to the unborn child.
If the patient is pregnant, suspects she may be pregnant, or plans to become pregnant, she should consult the 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 infant.
Breastfeeding must be discontinued during treatment with this medicine.
If the patient is breastfeeding, she should consult the doctor or pharmacist before using this medicine.
Effects on fertility
No studies have been conducted on effects on fertility; however, this medicine may affect fertility. Discuss with the doctor the possible risks associated with taking this medicine and options for preserving the patient’s ability to have children in the future.
Driving and operating machinery
In some cases, Irinotecan may cause adverse effects that may affect the ability to drive and operate machinery. If in doubt, consult the doctor or pharmacist.
Dizziness or vision problems may occur within 24 hours after administration of Irinotecan. If such adverse effects occur, do not drive or operate machinery until they resolve.
Irinotecan SUN contains sorbitol
Sorbitol is a source of fructose.
If the patient has previously been diagnosed with hereditary fructose intolerance, a rare genetic disorder, the patient must not take this medicine. In patients with hereditary fructose intolerance, the body cannot break down the fructose contained in this medicine, which may cause severe adverse effects.
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If the patient has hereditary fructose intolerance, inform the doctor before starting treatment.
Irinotecan contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to use Irinotecan

If Irinotecan is prescribed to the patient, the medicine will be administered only by physicians or nurses experienced in the administration of chemotherapy.
Method of administration
Irinotecan is given as an intravenous infusion (drip) lasting from 30 to 90 minutes.
During administration of Irinotecan, the patient may also receive other medicines intended to prevent nausea, vomiting, diarrhoea and other adverse effects.
These medicines may need to be continued for at least one day after the Irinotecan infusion.
Patients should inform healthcare professionals if they experience stinging, pain or swelling around the site of the intravenous needle during administration of Irinotecan.
Leakage of the medicine outside the vein may cause tissue damage. If pain, redness or swelling occurs around the intravenous needle site during administration of Irinotecan, medical personnel must be informed immediately.
What is the dose of Irinotecan
The dose of Irinotecan depends on many factors, including the treatment regimen, body size, age, general health status, blood count results, liver function, abdominal/pelvic radiotherapy, and presence of adverse effects such as diarrhoea. The physician will calculate the body surface area in square metres (m²).

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

In patients receiving Irinotecan in combination with cetuximab, Irinotecan must not be administered earlier than 1 hour after completion of the cetuximab infusion.
The duration of treatment can only be determined by the treating physician.
The number of infusions will depend on the patient's response to treatment. This will be discussed with the patient by the treating physician.
Administration of a higher than recommended dose of Irinotecan
If the patient believes they have received too high a dose of Irinotecan, they should seek immediate medical help. Overdose intensifies adverse effects such as diarrhoea or neutropenia (reduced number of white blood cells in the blood). In such a case, the patient will receive treatment aimed at preventing dehydration. White blood cell counts will be monitored, and any infections will be treated as appropriate.
Missed administration of Irinotecan
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If an appointment for Irinotecan infusion is missed, the patient should contact their physician to obtain instructions.
If there are any further doubts regarding the use of this medicine, the patient should consult their physician, pharmacist or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Your doctor will discuss these adverse effects with you and explain the risks and benefits of treatment.
Some adverse effects may be serious. Contact your doctor immediately if any of the following serious adverse effects occur (see section 2).
Seek immediate medical help if you experience any symptoms of an allergic reaction: hives; difficulty breathing; swelling of the face, lips, tongue or throat.

• Diarrhoea (see section 2).
• Early-onset diarrhoea: occurs within 24 hours after taking the medicine, with symptoms such as runny nose, increased salivation, tearing, sweating, flushing, and abdominal cramps. (This reaction may occur during infusion. In such a case, inform medical staff immediately. Medicines may be given to stop and/or reduce these symptoms).
• Late-onset diarrhoea: occurs more than 24 hours after administration of the medicine. Because diarrhoea may lead to dehydration and electrolyte imbalance, it is important that the patient remains in contact with a healthcare professional to monitor health status and receive advice on medication and dietary modifications.

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

| Symptoms | Frequency* in monotherapy | Frequency in combination therapy | |--------------|-------------------------------|--------------------------------------| | Low white blood cell count increasing risk of infection | Very common | Very common | | Low red blood cell count causing fatigue and shortness of breath | Very common | Very common | | Loss of appetite | Very common | Very common | | Cholinergic syndrome (see section 2: "Warnings and precautions") | Very common | Very common | | Vomiting | Very common | Very common | | Nausea | Very common | Very common | | Abdominal pain | Very common | Common | | Hair loss (reversible) | Very common | Very common | | Mucositis (inflammation of mucous membranes) | Very common | Very common |

| Symptoms | Frequency* in monotherapy | Frequency in combination therapy | |--------------|-------------------------------|--------------------------------------| | Fever | Very common | Common | | Weakness and lack of energy | Very common | Very common | | Low platelet count (involved in blood clotting) leading to bruising or bleeding | Common | Very common | | Abnormal liver function tests | Common | Very common | | Infection | Common | Common | | Low white blood cell count with fever | Common | Common | | Constipation | Common | Common | | Abnormal kidney function tests | Common | Not reported |

Frequency unknown: frequency cannot be estimated from available data:

• Severe, persistent or bloody diarrhoea (which may be accompanied by abdominal pain or fever) caused by a bacterium called Clostridium difficile
• Blood infection (septicaemia)
• Dehydration (due to diarrhoea and vomiting)
• Dizziness, rapid heartbeat and pale skin (a condition called hypovolaemia)
• Allergic reaction
• Transient speech disturbances during or shortly after treatment
• Tingling sensations (paraesthesia)
• High blood pressure (during or after infusion)
• Heart problems*
• Lung disease causing wheezing and shortness of breath (see section 2)
• Hiccups
• Bowel obstruction
• Enlargement of the large intestine (colonic dilation)
• Gastrointestinal bleeding
• Inflammation of the large intestine (colitis)
• Abnormal laboratory test results
• Bowel perforation
• Fatty liver (hepatic steatosis)
• Skin reactions
• Reactions at the site of medicine administration
• Low potassium levels in the blood
• Low blood salt levels, mainly due to diarrhoea 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 diarrhoea and/or vomiting or blood infections.

If the patient is receiving Irinotecan in combination with cetuximab, some of the adverse effects experienced may be related to the use of this combination. These may include acne-like rash. Therefore, please also read the patient information leaflet for cetuximab.

If the patient is receiving Irinotecan in combination with capecitabine, some of the adverse effects experienced may be related to the use of this combination. These may include: very common blood clots (thromboembolism), common allergic reactions, heart attack, and fever in patients with low white blood cell count. Therefore, please also read the patient information leaflet for capecitabine.

If the patient is receiving Irinotecan in combination with capecitabine and bevacizumab, some of the adverse effects experienced may be related to the use of this combination. These may include: decreased white blood cell count, blood clots, high blood pressure, and heart attack. Therefore, please also read the patient information leaflet for capecitabine and bevacizumab.

Reporting of adverse effects

If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse.

Adverse effects 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
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse effects can also be reported to the marketing authorisation holder.

Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Irinotecan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the infusion bag and
outer packaging following EXP. The expiry date refers to the last day of the stated month.
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 must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Irinotecan contains

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

One infusion bag with a volume of 180 ml contains 270 mg of irinotecan hydrochloride trihydrate
(corresponding to 234 mg of irinotecan).
One infusion bag with a volume of 200 ml contains 300 mg of irinotecan hydrochloride trihydrate
(corresponding to 260 mg of irinotecan).
One infusion bag with a volume of 220 ml contains 330 mg of irinotecan hydrochloride trihydrate
(corresponding to 286 mg of irinotecan).
One infusion bag with a volume of 240 ml contains 360 mg of irinotecan hydrochloride trihydrate
(corresponding to 312 mg of irinotecan).
One millilitre of infusion solution contains 1.5 mg of irinotecan hydrochloride trihydrate
(corresponding 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 free from visible solid particles.
Irinotecan infusion solution is supplied in cardboard boxes containing 1, 5 or 10 bags, each containing a single dose of 180 ml, 200 ml, 220 ml or 240 ml.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sun Pharmaceutical Industries Europe BV
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

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

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
DE/H/5810/1/II/004 & DE/H/5810/001/IB/005
Denmark: Irinotecan SUN
Finland: Irinotecan SUN
Germany: Irinotecan SUN
Spain: Irinotecán SUN
France: Irinotecan SUN
Italy: Irinotecan SUN
Romania: Irinotecan SUN
Sweden: Irinotecan SUN
United Kingdom (Northern Ireland): Irinotecan

To obtain further information about this medicinal product, please contact the representative of the Marketing Authorisation Holder:
Ranbaxy (Poland) Sp. z o.o.
ul. Kubickiego 11
02-954 Warszawa
tel. 22 642 07 75
DE/H/5810/1/II/004 & DE/H/5810/001/IB/005

Information intended exclusively for healthcare professionals:

Preparation for use

• Calculate the dose and determine the appropriate size of the Irinotecan SUN infusion bag required for administration.
• Check the packaging for any signs of damage. Do not use if there are visible signs of tampering.
• Apply a patient information label to the protective pouch.

Removing the infusion bag from the protective pouch and inspection of the infusion bag

• Tear the protective pouch at the cut mark. Do not use if the protective pouch has been previously opened or is damaged.
• Remove the infusion bag from the protective pouch.
• Use only if the bag and seal are intact. Before administration, firmly squeeze the bag to check for leaks. If leakage is detected, discard the bag and solution, as sterility may have been compromised.
• Parenteral medicinal products should be inspected visually for particulate matter or discoloration prior to administration. Do not administer if particulate matter or discoloration is observed.

Administration

• Break the seal of the closure by pressing with the hand on one side.
• Under aseptic conditions, connect a sterile administration set.
• Follow the instructions provided with the administration set.

Precautions

• Do not use in series connections (piggyback).
• Do not add any supplementary substances to the infusion bag.
• The infusion solution is ready for use and must not be mixed with other medicinal products.
• Irinotecan SUN infusion solution is for intravenous use only.

Personnel should be equipped with appropriate protective materials, including long-sleeved gowns, protective masks, caps, protective goggles, sterile disposable gloves, protective drapes to cover the work area, and waste collection bags.
Cytotoxic agents must not be handled by pregnant healthcare personnel.
Contact with the eyes may cause severe irritation. In such cases, immediately rinse the eyes thoroughly with water. If irritation persists, seek medical advice. In case of contact with the skin, wash the affected area thoroughly with water. Exercise caution when handling excreta and vomit.

Disposal
Any unused medicinal product or waste materials must be disposed of in accordance with local procedures for the disposal of cytotoxic waste.