IRINTO 20 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. What is Irinto and what is it used for
2. What you need to know before you use Irinto
3. Irinto will only be administered in units specializing in the administration of
   1. How to use Irinto
   2. Possible side effects
   3. How to store Irinto
   4. Contents of the pack and other information

Irinto 20 mg/ml concentrate for solution for infusion
Irinotecan hydrochloride trihydrate
Generic medicine

Read this leaflet carefully before you use 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
• This medicine has been prescribed only for you. Never give it to others, even if their symptoms are the same as yours, because it could be dangerous.
• If you get any side effects, tell your doctor or pharmacist This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What is Irinto and what is it used for

Irinto belongs to a group of medicines called cytotoxic antineoplastic agents
(anti-tumor medicines).
Irinto is indicated for the treatment of adult patients with advanced colorectal cancer, both
in combination with other medicines or alone.

2. What you need to know before you use Irinto

Do not use Irinto:

• If you are allergic (hypersensitive) to the active ingredient (irinotecan hydrochloride trihydrate) or to any of the excipients of Irinto (listed in section 6).
• If you suffer from a chronic inflammatory bowel disease or intestinal obstruction
• If you are breastfeeding
• If you have liver problems with increased levels of bilirubin in the blood (more than three times the upper limit of the normal range)
• If you suffer from severe blood cell failure (severe bone marrow failure)
• If your general health condition is poor (determined according to international WHO standards greater than 2)
• If you are using any medicine or herbal extract containing St. John's Wort (a medicine against depression)

If you receive Irinto in association with 5-fluorouracil capecitabine, cetuximab or
bevacizumab, make sure you also read the package leaflets of these medicines.

Warnings and precautions:
Talk to your doctor or pharmacist before using Irinto.

Irinto will only be administered in units specializing in the administration of

anticancer drugs (cytotoxic antineoplastic chemotherapeutics), under the supervision
of a doctor qualified to use these drugs.
The unit staff will explain what precautions to take during and after the
This medicine is intended for use in adults only.
Check with your doctor if this medicine has been prescribed for use in a
child.
Particular attention must also be paid to elderly patients.

During the administration of Irinto (30-90min.) and up to 24 hours after the
administrationyou may experience some of the following symptoms: diarrhea, sweating,
abdominal pain, visual disturbances, excessive salivation. The medical term for these
symptoms is “acute cholinergic syndrome” which can be treated (with atropine).
If you experience any of these symptoms, inform your doctor immediately who will
give you the most appropriate treatment.

From the first day after treatment with Irinto and until the nexttreatmentyou may
experience several symptoms, which may be severe and require immediate treatment
and careful supervision.

Diarrhea
If diarrhea starts more than 24 hours after the administration of Irinto (“delayed diarrhea”)
it can be severe. It often occurs around 5 days after therapy. This diarrhea
must be treated immediately and kept under strict control. Immediately
after the first diarrheal discharge, follow these instructions:

• 1. Take the anti-diarrheal treatment that your doctor has given you, following the instructions received carefully. The treatment should not be changed without first consulting your doctor. The recommended anti-diarrheal treatment is loperamide (4mg the first time and then 2mg every 2 hours, even at night). This should be continued for at least 12 hours after the last diarrheal discharge. The recommended dosage for loperamide should not be taken for more than 48 hours.
• 2. Immediately drink large amounts of water, rehydrating fluids (e.g. water, carbonated drinks, broth or oral rehydration therapy).
• 3. Immediately inform the doctor supervising the treatment of the diarrhea. If you are unable to reach them, contact the hospital and the operating unit supervising the treatment with Irinto. It is very important that they are informed of the diarrhea.

For the management of diarrhea, hospitalization is recommended in the following cases:

• You suffer from diarrhea and have a fever (above 38°C)
• You have severe diarrhea (and vomiting) with excessive water loss requiring intravenous hydration
• You still have diarrhea after 48 hours from the start of anti-diarrheal treatment

Note!Do not follow other treatments and intake of fluids for diarrhea other than those
prescribed by your doctor. Follow the doctor's instructions. Even if you have experienced delayed diarrhea in previous cycles, the anti-diarrheal treatment should not be used for
prevention.

Blood monitoring
Irinotecan can cause a decrease in the number of some of your white blood cells,
which play an important role in fighting infections. This is called
neutropenia. Neutropenia is often observed during treatment with irinotecan and is
reversible. The doctor should arrange for you to have regular blood tests to
monitor these white blood cells. Neutropenia is severe and must be treated
immediately and carefully monitored.

Fever
If you have a fever higher than 38°C, contact your doctor or hospital immediately
to start the necessary treatment.

Difficulty breathing
If you have difficulty breathing, contact your doctor immediately.

Impairment of liver function
Before starting treatment with Irinto and before each treatment cycle, the doctor
checks liver function (through blood tests).

Nausea (feeling unwell) and vomiting
If you have nausea and/or vomiting, contact your doctor or the hospital unit immediately.

Impairment of kidney function
Since this medicine has not been tested in patients with kidney problems, check with
your doctor if you have any kidney problems.

Cardiac disorders
If you have heart problems or additional risk factors such as smoking, high blood pressure or high cholesterol levels, your doctor will monitor your condition.

Increased susceptibility to infections
Chemotherapeutic agents can weaken your immune system. Particular attention should be paid when administering live or attenuated vaccines. Vaccination
with live vaccines should be avoided.

Changes in blood composition
Given the risk of changes in blood composition, your doctor will perform blood tests
on a weekly basis.

Dehydration
Rare cases of renal failure, hypotension and circulatory failure have been
observed in patients who have had episodes of dehydration associated with diarrhea and/or
vomiting, or sepsis.

Other medicines and Irinto
Tell your doctor or pharmacist if you are taking, have recently taken or may
take any other medicine.
The following medications can alter the effects of Irinto and therefore should not
be administered at the same time:

• carbamazepine, phenobarbital or phenytoin (drugs used in the management of epilepsy)
• ketoconazole (used in the treatment of fungal infections)
• rifampicin (used in the treatment of tuberculosis)
• warfarin (an anticoagulant used to thin the blood)
• Atazanavir (used for the treatment of HIV)
• Vaccines (the response to the killed or inactivated vaccine may be diminished)
• Cyclosporine or tacrolimus (used to suppress the immune system)

Natural medicines based on St. John's Wort ( Hypericum perforatum) should not
be administered at the same time as Irinto, even between treatment cycles
because it can reduce the effects of Irinto. If you are taking St. John's Wort preparations, stop immediately and inform your doctor.
The following medicines may be affected by Irinto:

• Muscle relaxants used during operations (e.g. succamethonium, non-depolarizing agents), as Irinto may prolong or block their effects. If you are to be operated on, inform your doctor or anesthesiologist that you are taking this medicine.

Pregnancy and breastfeeding:
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have
a baby, ask your doctor for advice before taking this medicine

Pregnancy
You should not receive Irinto if you are pregnant unless it is clearly required.
If you are of childbearing potential and are receiving treatment with Irinto, you should be advised to
avoid pregnancy. Contraceptive measures should be taken by both male and female patients during treatment and for 3 months after the end of treatment.
In addition, if you become pregnant during this period, you should immediately inform your
doctor.

Breastfeeding
It is not known whether Irinotecan is excreted in human milk. Therefore, you should not breastfeed if
you are being treated with Irinto.

Driving and using machines
Since dizziness or visual disturbances may occur within 24 hours
after the administration of Irinto, you should not drive vehicles or operate machinery if
these symptoms occur. Contact your doctor or pharmacist if you have any doubts.

Irinotecan Hikma contains sorbitol.
This medicine contains 45 mg of sorbitol in each millilitre of solution.
Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) should not receive this
medicine. Patients with HFI cannot break down fructose, which can cause
serious side effects.
You should inform your doctor before receiving this medicine if (or your child) has HFI or
if your child can no longer take sweet foods or drinks because they feel sick, vomit
or get unpleasant effects such as bloating, stomach cramps or diarrhea.
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

Irinto will be administered to you by intravenous infusion over a period of 30-90
minutes.
The dose will depend on your age, height, weight and overall clinical condition. The dosage
also depends on any other treatments you may have received for your tumor. Your
doctor will calculate your body surface area in square meters (m²).

• If you have already been treated with 5-fluorouracil, you will normally be treated with only Irinto starting with a dose of 350 mg/m every three weeks.
• If you have never been treated with chemotherapy, you will normally receive 180 mg/m of Irinto every two weeks followed by folinic acid and 5-fluorouracil.

of cetuximab. Irinto cannot be administered within one hour of the end
of the cetuximab infusion.
Always follow your doctor's advice regarding ongoing treatment.
If you receive Irinto in combination with bevacizumab, please consult the
package leaflet of bevacizumab.
These dosages may be modified by your doctor depending on your condition and
any side effects you may experience.
capecitabine. These dosages may be modified by the doctor depending on the
conditions and side effects you may experience.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Your doctor will inform you about these side effects and explain the risks and benefits of the
treatment.
Some of these side effects must be treated immediately.

Very common side effects (in more than 1 in 10 patients)
IN MONOTHERAPY:

• Neutropenia (reduced white blood cell count) which increases the risk of infections
• Anemia (reduction in the number of red blood cells) which can make the skin pale and cause weakness and difficulty breathing
• Loss of appetite
• Cholinergic syndrome: the main symptoms were defined as initial diarrhea and other various symptoms such as abdominal pain, red, painful, itchy or watery eyes (conjunctivitis), runny nose (rhinitis), low blood pressure (hypotension), dilation of blood vessels (vasodilation), swelling, chills, a general feeling of weakness (malaise), dizziness, visual disturbances, pupil constriction (miosis), watery eyes (lacrimation) and increased salivation that occurs during or within the first 24 hours after the infusion of Irinto. These symptoms disappear after administration of atropine.
• Diarrhea
• Vomiting
• Nausea
• Abdominal pain
• Hair loss (hair will grow back after treatment ends)
• Inflammation of the mucous membranes
• Fever
• Asthenia (lack or loss of strength)

IN COMBINATION THERAPY

• Thrombocytopenia (reduction in the number of blood platelets) which causes bruising, a tendency to bleed and abnormal bleeding
• neutropenia
• anemia
• loss of appetite
• cholinergic syndrome: the main symptoms were defined as initial diarrhea and other various symptoms such as abdominal pain, red, painful, itchy or watery eyes (conjunctivitis), runny nose (rhinitis), low blood pressure (hypotension), dilation of blood vessels (vasodilation), swelling, chills, a general feeling of weakness (malaise), dizziness, visual disturbances, pupil constriction (miosis), watery eyes (lacrimation) and increased salivation that occurs during or within the first 24 hours after the infusion of Irinto. These symptoms disappear after administration of atropine.
• diarrhea
• vomiting
• nausea
• hair loss (hair grows back at the end of treatment)
• inflammation of the mucous membranes
• asthenia (loss or lack of strength)
• Transient and mild to moderate increase in serum levels of certain liver enzymes (SGPT, SGOT, alkaline phosphatase) or bilirubin

Common side effects (in less than 1 in 10 patients but more than 1 in 100)
IN MONOTHERAPY

• Infection
• Thrombocytopenia (reduction in the number of blood platelets) which causes bruising, a tendency to bleed and abnormal bleeding
• Fever associated with a severe reduction in the number of certain white blood cells (febrile neutropenia)
• Constipation
• Transient and mild to moderate increase in serum levels of creatinine
• Transient and mild to moderate increase in serum levels of certain liver enzymes (transaminases, alkaline phosphatase) or bilirubin

IN COMBINATION THERAPY

• infection
• fever associated with a severe reduction in the number of certain white blood cells (febrile neutropenia)
• abdominal pain
• constipation
• fever

Rare side effects (in less than 1 in 1,000 patients but more than 1 in 10,000)
IN COMBINATION THERAPY

• hypokalemia and hyponatremia mainly related to diarrhea and vomiting

Frequency not known (cannot be estimated on the basis of available data)

• inflammation of the intestine causing abdominal pain and/or diarrhea (a condition known as pseudomembranous colitis)
• sepsis (a life-threatening condition that arises when the body's response to infection causes damage to its own tissues and organs)
• peripheral thrombocytopenia with antiplatelet antibodies
• loss of water (dehydration), commonly associated with diarrhea and/or vomiting
• hypovolemia (reduction in plasma volume)
• hypersensitivity (allergic) reactions
• severe allergic reactions (anaphylactic/anaphylactoid reactions) including swelling of the hands, feet, ankles, face, lips, mouth and throat which can cause difficulty swallowing or breathing. Contact your doctor immediately if you experience any of these symptoms.
• Anaphylactic reactions
• Transient speech disorders, in some cases the event has been attributed to the cholinergic syndrome observed during or shortly after the infusion of irinotecan
• Early effects such as muscle contraction or cramps and numbness (paresthesia)
• Increased blood pressure (hypertension) during or after the infusion
• Kidney problems (renal failure), low blood pressure (hypotension) or collapse (cardiovascular failure), in patients who have experienced episodes of dehydration associated with diarrhea and/or vomiting or sepsis.
• Lung disease (interstitial lung disease) which presents with shortness of breath, dry cough and wheezing sounds
• Difficulty breathing
• Hiccups (involuntary contraction of the diaphragm that can repeat several times in a minute)
• Partial or complete blockage of the intestine (intestinal obstruction, ileus)
• Gastrointestinal bleeding or hemorrhage
• Inflammation of the large intestine causing abdominal pain (including colitis, typhlitis, ischemic and ulcerative colitis)
• Abnormal dilation of the colon (megacolon)
• Elevated pancreatic enzymes symptomatic or asymptomatic
• Intestinal perforation
• Skin reactions
• Injection site reactions
• Increased levels of certain digestive enzymes that break down sugars (amylase) or fats (lipase)
• Hypokalemia
• Hyponatremia mainly related to diarrhea and vomiting
• Increased serum levels of certain liver enzymes (transaminases, e.g. AST and ALT) in the absence of progressive liver metastases have been rarely reported
• Muscle contraction or cramps

If you receive Irinto in combination with cetuximab, some of the side effects you may experience may be secondary to this combination. Therefore, make sure
If you receive irinotecan in combination with capecitabine, some of the side effects you may experience may be secondary to this combination. These
side effects may include: very common blood clots, common allergic reactions, heart attack and fever in patients with a low white blood cell count.
capecitabine.
If you receive irinotecan in combination with capecitabine and bevacizumab, some of the side effects you may experience may be secondary to this combination. These
side effects may include: reduced number of white blood cells, blood clots, high blood pressure and heart attacks. Therefore, make sure to read

You must tell your doctor if you experience:

• early diarrhea with associated symptoms referred to as "acute cholinergic syndrome" (see section 2)
• late-onset diarrhea
• diarrhea that persists for 48 hours after the start of treatment
• fever
• nausea, vomiting
• respiratory disturbances, unproductive cough, symptoms of crackles in the lungs

Hospitalization of the patient is indicated in the following situations

• Coexisting diarrhea and fever (above 38°C)
• Severe diarrhea (and vomiting) with clinical characteristics of excessive dehydration (intravenous fluid replacement is necessary)
• Diarrhea that does not subside within 48 hours of the start of treatment

Reporting of side effects
If you get any side effect, even if not listed in this leaflet, tell your doctor or pharmacist. Side effects can also be reported directly through the national reporting system at
www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa ..Reporting side effects helps to provide more information about 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
Store in the original packaging to protect the medicine from light
For single use only
After dilution with 5% glucose, physical and chemical stability has been demonstrated for
24 hours, if stored between 2-8ºC and for 12 hours if stored at 25 ± 2ºC, protected from light.
After dilution with 0.9% sodium chloride, physical and chemical stability has been
demonstrated for 12 hours if stored at 25 ± 2ºC, protected from light.
Irinto must be diluted and used immediately after opening.
From a microbiological point of view, unless the dilution method precludes the
risk of microbial contamination, the product must be used immediately.
If not used immediately, the storage times and conditions in use are
the responsibility of the user.
Do not use this medicine after the expiry date which is indicated 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 in the wastewater and household waste. Ask your
pharmacist how to dispose of medicines no longer needed. These measures contribute
to protecting the environment.

6. Contents of the pack and other information

What Irinto contains
The active ingredient of 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 2ml vial contains 40mg of irinotecan hydrochloride trihydrate
A 5ml vial contains 100mg of irinotecan hydrochloride trihydrate
A 15ml vial contains 300mg of irinotecan hydrochloride trihydrate
A 25ml vial contains 500mg of irinotecan hydrochloride trihydrate
The other ingredients are sorbitol (E420), lactic acid, sodium hydroxide and/or hydrochloric
acid (to adjust the pH to 3.5) and water for injections.
Irinotecan Hikma is a clear and transparent solution.
pH: 3.0 - 4.0
Osmolality: 265-350 mosmol / kg

Description of the appearance of Irinto and contents of the pack
Amber glass vial, with FluroTec or equivalent rubber stoppers and an aluminium flip-off
cap.
Packaging:
Pack with 1 vial of 2ml
Pack with 1 vial of 5ml
Pack with 1 vial of 15ml
Pack with 1 vial of 25ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A e 8B
Fervença
2705-906 Terrugem SNT
Portugal
Tel: +351 21 980 84 10
Fax: +351 21 961 51 02
e-mail: portugal [email protected]
Thymoorgan Pharmazie GmbH
Schiffgraben 23
D-38690 Goslar
Germany
Tel: +49(0) 5324 7701-0
Fax: +49(0) 5324 7701-30
The following information is intended exclusively for healthcare professionals
Irinto 20mg/ml, concentrate for solution for infusion
Irinotecan hydrochloride trihydrate
Handling:
As with other antineoplastic/cytotoxic agents, Irinto must be prepared and
handled with caution. The use of goggles, mask and gloves is mandatory. If the
concentrated irinotecan solution for infusion or the solution prepared for infusion
should come into contact with the skin, wash immediately and thoroughly with
water and soap. If Irinto concentrate for infusion or the solution prepared for
infusion should come into contact with mucous membranes, wash immediately with water.
Instructions for dilution
As with all injectable drugs, the solution of Irinto 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, draw up the required amount of Irinto
concentrate solution from the vial using a graduated syringe and inject it into a bag or
bottle for infusion 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 protection during dilution
Preparation must be carried out in a defined area for handling 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 glasses, headgear, gown and gloves and disposable masks.
Open containers such as injection and infusion bottles and tubes, syringes, catheters
and used tubes, as well as cytotoxic waste, must be considered hazardous waste and
disposed of in accordance with local guidelines for the management of hazardous waste.
In case of spillage, protective clothing must be used. Broken glass must be
collected and placed in containers for special waste. Contaminated surfaces must be
properly rinsed with plenty of cold water and washed carefully.
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, wash the affected area thoroughly with water. If you feel any discomfort, contact your doctor. If Irinto comes into contact with the eyes, wash them thoroughly with a large amount of water. Contact
the ophthalmologist immediately.
Disposal
All materials used for dilution and administration must be disposed of
according to standard hospital procedures applicable to cytotoxic medicines.