Irinto

Package Leaflet: Information for the User

Irinto 20 mg/ml concentrate for solution for infusion

Irinotecan hydrochloride trihydrate
Generic medicine
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any 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.

What is in this leaflet:

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

1. What Irinto is and what it is used for

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

2. What you must know before using Irinto

Do not use Irinto:
➢ If you are allergic (hypersensitive) to the active substance (irinotecan hydrochloride trihydrate) or to
any of the excipients of Irinto (listed in section 6).
➢ If you have chronic inflammatory bowel disease or intestinal obstruction
➢ If you are a woman who is breastfeeding (see section 2)
➢ If your bilirubin level is more than three times the upper limit of the normal range
➢ If you have severe bone marrow dysfunction
➢ If your general health status is poor (as determined by international WHO standards greater than 2)
➢ If you are currently taking or have recently taken St. John’s wort (herbal extract containing Hypericum)
➢ If you are currently receiving 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 Irinto in combination with other medicines, make sure to read the package leaflet of these other medicines for additional contraindications.
Warnings and precautions:
Talk to your doctor or pharmacist before using Irinto
➢ if you have Gilbert’s syndrome, an inherited condition that may cause elevated bilirubin levels and jaundice (yellowing of the skin and eyes).
Exercise particular caution with irinotecan. The use of irinotecan should be restricted to specialized units experienced in administering cytotoxic chemotherapy, and the medicine should only be administered under the supervision of a physician experienced in anticancer chemotherapy.
Diarrhea
Irinotecan may cause diarrhea, which in some cases can be severe. This may occur a few hours or a couple of days after infusion of the medicine. If left untreated, it may lead to dehydration and serious chemical imbalances, which can be life-threatening. Your doctor will prescribe medications to help prevent or control this side effect. Make sure to obtain the medication promptly so you have it at home when needed.

• Take the prescribed medication at the first sign of loose or frequent bowel movements.
• Drink large amounts of water and (or) electrolyte-containing beverages (soda 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 feel dizzy, lightheaded, or faint.

Neutropenia (reduction in the number of certain white blood cells)
This medicine may reduce the number of certain white blood cells, especially in the weeks following administration. This may increase the risk of developing an infection. Inform your doctor or nurse immediately if you experience signs of infection such as fever (38°C or higher), chills, pain during urination, new cough, or sputum production. Avoid close contact with sick people or those with infections. Inform your doctor immediately if signs of infection occur.
Blood monitoring
Your doctor will likely perform blood tests before and during treatment to monitor the effects of the drug on blood counts or blood chemistry. Based on test results, additional medications may be needed to manage side effects. Your doctor may also need to reduce or delay the next dose of this medicine, or even discontinue treatment altogether. Attend all scheduled medical appointments and laboratory tests.
This medicine may lower platelet counts in the weeks following administration, increasing the risk of bleeding. Consult your doctor before taking any medicines or supplements that may affect the body’s ability to stop bleeding, such as aspirin or aspirin-containing products, warfarin, or vitamin E. Inform your doctor immediately if you experience 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 of treatment or in the first few days afterward. Your doctor may administer a medication before treatment to help prevent nausea and vomiting. Your doctor will likely prescribe anti-nausea medications for you to take at home. Keep these medications readily available for when you need them. Call your doctor if you are unable to take fluids orally due to nausea and vomiting.
Acute cholinergic syndrome
This medicine may affect part of the nervous system that controls bodily secretions, causing what is known as cholinergic syndrome. Symptoms may include runny nose, increased salivation, excessive tearing, sweating, hot flashes, abdominal cramps, and diarrhea. If you experience any of these symptoms, inform your doctor or nurse immediately, as medications are available to help control them.
Pulmonary disorders
Rarely, people taking this drug may develop serious lung problems; inform your doctor immediately if you develop a new 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 significant 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, shortness of breath, swelling, pain, redness, or warmth in one arm or leg.
Chronic intestinal inflammation and/or intestinal obstruction
Call your doctor if you have abdominal pain or reduced intestinal motility, especially if accompanied by bloating and loss of appetite.
Radiation therapy
If you have recently received pelvic or abdominal radiotherapy, you may have an increased risk of developing bone marrow suppression. Discuss with your doctor before starting irinotecan.
Renal function
Cases of renal dysfunction have been reported.
Cardiac disorders
Inform your doctor if you have or have had heart disease or if you have previously taken anticancer medicines. Your doctor will closely monitor you and discuss ways to reduce risk factors (e.g., smoking, hypertension, high fat levels).
Vascular disorders
Irinotecan is rarely associated with blood flow disorders (blood clots in vessels of the legs and lungs) and may rarely occur in patients with multiple risk factors.
Other
This drug may cause sores in the mouth or on the lips, often within the first weeks after starting treatment. This may cause mouth pain, bleeding, or even difficulty eating. Your doctor or nurse may suggest ways to reduce this problem, such as changing how you eat or brush your teeth. If necessary, your doctor may prescribe a medication to relieve pain.
For information on contraception, pregnancy, breastfeeding, and fertility, refer to the
information provided under the section Contraception, pregnancy, breastfeeding, and
fertility.
Information provided under the section Contraception, pregnancy, breastfeeding, and fertility.
Inform your doctor or dentist that you are taking this medicine if you are planning to undergo surgery or any procedure.
If used in combination with other anticancer drugs for your condition, make sure to read the package leaflets of the other drugs as well.
If your doctor has told you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.
Other medicines and Irinto
Irinto may interact with various medicines and supplements, which may increase or decrease the level of the medicine in the blood. Inform your doctor or pharmacist if you are using, have recently used, or might use any of the following medicines:

• 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 (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 body’s 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/folic acid
• Bevacizumab (a blood vessel growth inhibitor)
• Cetuximab (an EGF receptor inhibitor)

Inform your doctor, pharmacist, or nurse before using Irinto if you are receiving or have recently received chemotherapy (and radiotherapy).
Do not start or stop any medicine while taking irinotecan without first consulting your doctor.
This medicine may cause severe diarrhea. Try to avoid laxatives and stool softeners while taking this medicine.
There may be many medicines that interact with irinotecan. Check with your doctor, pharmacist, or nurse about other medicines, herbs, supplements, and alcohol that may cause problems with this medicine.
Contraception, pregnancy, breastfeeding, and fertility:
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before taking this medicine.
Contraception
If you are a woman of childbearing potential, you must use an effective method of contraception during treatment and for 6 months after stopping treatment.
As a man, you must use effective contraception during treatment and for 3 months after stopping treatment. It is important to consult your doctor about which types of birth control can be used with this medicine.
Pregnancy
This medicine may harm the fetus if taken at the time of conception or during pregnancy. Before starting treatment, your doctor will ensure you are not pregnant.
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before taking this medicine.
Breastfeeding
Irinotecan and its metabolite have been detected in human milk. Breastfeeding must be discontinued for the duration of treatment with this medicine.
If you are breastfeeding, consult your doctor or pharmacist before taking any medicine.
Fertility
No studies have been conducted; however, this medicine may affect fertility. Before taking this medicine, discuss with your doctor the potential risks and options for preserving your ability to have children.
Driving and using machines
During the first 24 hours after administration of this medicine, you may experience dizziness or visual disturbances. In this case, do not drive and do not operate tools or machinery.
This medicine contains sorbitol.
This medicine contains a sugar (sorbitol). Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not receive this medicine. Patients with HFI cannot break down fructose, which may cause serious side effects.
You must inform your doctor before receiving this medicine if (or your child) has HFI or if your child can no longer tolerate sweet foods or drinks because they feel unwell, vomit, or experience unpleasant effects such as bloating, stomach cramps, or diarrhea.
This medicine contains 45 mg of sorbitol per ml, equivalent to 90 mg/2 ml, 225 mg/5 ml, 675 mg/15 ml, and 1125 mg/25 ml.
This medicine contains sodium.
This medicine contains less than 1 mmol of sodium (23 mg) per ml of solution, i.e., essentially "sodium-free".

3. How to use Irinto

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
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 after taking this medicine.
The amount of Irinto you will receive depends on many factors, including height and weight, general health or other medical conditions, and the type of cancer or condition being treated.
Your doctor will determine the dose and schedule. Irinto is injected into a vein intravenously (IV). You will receive this injection at a clinic or in hospital. Irinto must be administered slowly, and the intravenous infusion may take up to 90 minutes to complete.
You may be given other medicines to prevent nausea, vomiting, diarrhoea, and other side effects during treatment with Irinto. You may need to continue taking these medicines for at least one day after the Irinto injection.
Inform the healthcare staff if you feel burning, pain, or swelling around the intravenous needle when Irinto is being injected. If the medicine leaks out of the vein, it may cause tissue damage. If you feel pain or notice redness or swelling at the injection site while receiving Irinto, inform the healthcare staff immediately.
There are currently several recommended treatment regimens 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 a number of factors, including the treatment regimen, body size, age and general health status, blood counts, liver function, whether you have received radiation to the abdomen/pelvis, and whether you have experienced side effects such as diarrhoea.
Only your doctor can determine the duration of treatment.

If you use more Irinotecan than you should
Seek emergency medical help. Symptoms of overdose may include some of the serious side effects listed in this leaflet.

If you forget to use Irinotecan
Call your doctor for instructions if you miss an appointment for your Irinotecan injection.
If you have any questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets
them.
Some side effects may be serious. If you experience any of the following serious side
effects (see section 2), you must contact your doctor immediately.
Seek emergency medical help if you have any of the following signs of an allergic
reaction: hives; difficulty breathing; swelling of the face, lips, tongue or throat.

• Diarrhoea (see section 2).
• Early diarrhoea: occurs within 24 hours of taking the medicine, accompanied by symptoms such as runny nose, increased salivation, tearing, hot flushes, abdominal cramps. (This may occur while the medicine is being administered. If it occurs, inform healthcare personnel immediately. A medicine may be given to stop and/or reduce this early side effect.)
• Delayed diarrhoea: occurs more than 24 hours after taking the medicine. Since this may lead to dehydration and electrolyte imbalance due to diarrhoea, it is important to stay in contact with healthcare professionals for monitoring and advice regarding medicines and dietary changes.

Talk to your doctor or nurse if you experience any of the following symptoms:

* 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 or 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 pale skin (a condition called hypovolemia)
• Allergic reaction
• Temporary speech disturbances during or immediately after treatment
• Tingling sensations
• High blood pressure (during or after infusion)
• Heart problems*
• Lung disorder causing wheezing and shortness of breath (see section 2)
• Hiccups
• Bowel obstruction
• Enlarged colon
• Bleeding from the intestine
• Inflammation of the large intestine
• Abnormal laboratory test results
• Perforation (hole) in the intestine
• Fatty liver disease
• Skin reactions
• Reactions at the site where the medicine was administered
• Low level of potassium in the blood
• Low level of salt in the blood, particularly related to diarrhoea and vomiting
• Muscle cramps
• Kidney problems*
• Low blood pressure*
• Fungal infections
• Viral infections

* Uncommon cases of these events have been observed in patients who experienced
episodes of dehydration associated with diarrhoea and/or vomiting or blood infections.

Reporting of adverse reactions
If you get any adverse reactions, including ones not listed in this leaflet, talk to your doctor or pharmacist. Adverse reactions can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Irinto

Keep this medicine out of the sight and reach of children.
Store below 25°C.
Do not refrigerate or freeze.
Keep in the original packaging to protect the medicine from light.

After opening:
Chemical and physical in-use stability of the concentrate in the perforated vial has been demonstrated
for 28 days at room temperature, whether exposed to or protected from light, and for 28 days at 2–8°C,
when protected from light.
From a microbiological standpoint, unless the opening method excludes the risk of microbial contamination,
the product should be used immediately.
If not used immediately, the storage times and conditions during use are the responsibility of the user.

After dilution:
After dilution with 5% glucose, chemical and physical stability has been demonstrated for
24 hours when stored at 2–8°C and for 12 hours when stored at 25 ± 2°C, protected from light.
After dilution with 0.9% sodium chloride, chemical and physical stability has been demonstrated for
24 hours when stored at 2–8°C and for 12 hours when stored at 25 ± 2°C, protected from light.
Irinto must be diluted.
From a microbiological standpoint, unless the dilution method prevents the risk of microbial contamination,
the product should be used immediately.
If not used immediately, the storage times and conditions during use are the responsibility of the user.

Do not use this medicine after the expiry date stated on the outer packaging and on the vial label after EXP.
The expiry date refers to the last day of the month.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Package contents and other information

What Irinto contains
The active substance in Irinto is irinotecan hydrochloride trihydrate. 1 ml of concentrate contains
20 milligrams (mg) of irinotecan hydrochloride trihydrate (equivalent to 17.33 mg/ml 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 and/or hydrochloric
acid (to adjust pH to 3.5) and water for injections.
Irinto is a clear and transparent solution.
pH: 3.0 – 4.0
Osmolality: 265–320 mosmol/kg

Description of the appearance of Irinto and contents of the pack
Amber glass vial, with FluroTec rubber stoppers or equivalent and an aluminum flip-off cap.
Packaging:
Pack containing 1 vial of 2 ml
Pack containing 1 vial of 5 ml
Pack containing 1 vial of 15 ml
Pack containing 1 vial of 25 ml
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A and 8B
Fervença
2705-906 Terrugem SNT
Portugal
Tel: +351 21 980 84 10
e-mail: [email protected]

Manufacturer
Thymoorgan Pharmazie GmbH
Schiffgraben 23
D-38690 Goslar
Germany
Tel: +49(0) 5324 7701-0

Marketing Authorisation Holder in Italy
Hikma Italia SpA
Viale Certosa 10, 27100 Pavia

This medicinal product is authorised in the European Economic Area Member States under the following names:
Austria Irinotecan Hikma 20 mg/ml Concentrate for solution for infusion
Belgium Irinotecan Hikma 20 mg/ml
France Irinotecan Hikma 20 mg/ml, solution to be diluted for infusion
Germany Irinotecan Hikma 20 mg/ml Concentrate for solution for infusion
Italy Irinto
Netherlands Irinotecan HCl trihydrate Hikma 20 mg/ml concentrate for solution for infusion
Portugal Irinotecano Hikma
Spain Irinotecán Hikma 20 mg/ml Concentrado para Solución para perfusión EFG
United Kingdom / Northern Ireland Irinotecan 20 mg/ml Concentrate for solution for infusion

The following information is intended exclusively for healthcare professionals
Irinto 20 mg/ml, concentrate for solution for infusion
Irinotecan hydrochloride trihydrate

Handling:
As with other antineoplastic/cytotoxic agents, Irinto must be prepared and handled with care. The use of goggles, mask, and gloves is mandatory. If the solution of irinotecan concentrate for infusion or the prepared infusion solution comes into contact with the skin, wash immediately and thoroughly with water and soap. If the Irinto concentrate for infusion or the prepared infusion solution comes into contact with mucous membranes, rinse immediately with water.

Instructions for dilution
As with all injectable medicines, the Irinto solution must be prepared under aseptic conditions.
If any precipitate is observed in the vials or in the infusion solution, the product must be discarded following standard hospital procedures applicable to cytotoxic drugs.
Under aseptic conditions, withdraw the required amount of Irinto concentrate solution from the vial using a graduated syringe and inject it into an infusion bag or bottle of 250 ml containing either 0.9% sodium chloride solution or 5% glucose solution. The infusion must then be thoroughly mixed by manual rotation.

Instructions for protective measures during dilution
Preparation must be carried out in a designated area for handling hazardous drugs (preferably under a vertical laminar airflow system). The work area must be protected by covering it with disposable absorbent paper and plastic. Protective clothing must be worn: protective goggles, head cover, gown, gloves, and disposable masks.
Opened containers such as injection and infusion bottles, as well as tubing, syringes, catheters, and tubing used, together with cytotoxic waste, must be considered hazardous waste and disposed of in accordance with local guidelines for hazardous waste management.
In case of spillage, protective clothing must be worn. Broken glass must be collected and placed in containers for special waste. Contaminated surfaces must be properly rinsed with large amounts of cold water and thoroughly cleaned.
Materials used for cleaning must be disposed of as hazardous waste.
If Irinto comes into contact with the skin, the area must be rinsed thoroughly with running water and then washed with water and soap. In case of contact with mucous membranes, thoroughly rinse the affected area with water. If you experience any discomfort, contact your doctor. In case of eye contact with Irinto, rinse eyes thoroughly with a large amount of water. Contact an ophthalmologist immediately.

Disposal
All materials used for dilution and administration must be disposed of according to standard hospital procedures applicable to cytotoxic medicinal products.