IRINOTECAN HYDROCHLORIDE 20 MG / ML CONCENTRATE FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

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Package leaflet: Information for the user Irinotecan Hydrochloride 20 mg/ml concentrate for solution for infusion

irinotecan hydrochloride, trihydrate

Read all of this leaflet carefully before you start using this 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, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Irinotecan Hydrochloride is and what it is used for

• 2. What you need to know before you use Irinotecan Hydrochloride

• 3. How to use Irinotecan Hydrochloride

• 4. Possible side effects

• 5. How to store Irinotecan Hydrochloride

• 6. Contents of the pack and other information

1. what irinotecan hydrochloride is and what it is used for

Irinotecan Hydrochloride belongs to a group of medicines called cytostatics (anti-cancer medicines).

Irinotecan Hydrochloride is used for the treatment of advanced cancer of colon and rectum in adults and where the disease is at an advanced stage in the large intestine, either in combination with other medicines (combination therapy) or alone (monotherapy).

Your doctor may use a combination of irinotecan with 5-fluorouracil/fo­linic acid (5-FU/FA) and bevacizumab to treat your cancer of the colon and rectum.

Your doctor may use a combination of irinotecan with capecitabine with or without bevacizumab to treat your cancer of the colon and rectum.

Your doctor may use a combination of irinotecan with cetuximab to treat cancer of the large intestine (KRAS wild-type) that is of a certain type known to display cell markers referred to as epidermal growth factor receptors (EGFR) which are blocked by the monoclonal antibody.

If you need any further information on your condition, please ask your doctor.

2. what you need to know before you take irinotecan hydrochloridedo not use irinotecan hydrochloride: if you have any other bowel disease or a history of bowel obstruction

• if you are allergic to Irinotecan Hydrochloride trihydrate or any of the other ingredients of this medicine (listed in section 6 “What Irinotecan Hydrochloride contains”)
• if you are a pregnant or breast-feeding or if you think you might be pregnant (see section 2)
• if you have increased levels of bilirubin in the blood (more than 3 times the upper limit of the normal range)
• if you have an imbalance of your blood cells (severe bone marrow failure)
• if you are in poor general condition (evaluated by an international standard)
• if you are using the natural remedy St John’s Wort (a herbal extract containing Hypericum)
• if you are to take or have recently taken live attenuated vaccines (vaccines against yellow fever, chicken pox, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza) and during the 6 months after stopping chemotherapy

If you receive Irinotecan Hydrochloride in combination with other medicines, please make sure that you also read the package leaflet of the other medicines regarding additional contraindications.

Warnings and precautions

This medicine is intended for adults only. Check with your doctor if this medicine has been prescribed for use in a child.

Special care is also needed in elderly patients.

As Irinotecan Hydrochloride is an anti-cancer medicine it will be administered to you in a special unit and under supervision of a doctor qualified in the use of anti-cancer medicines. The units’ personnel will explain to you what you need to take special care of during and after the treatment. This leaflet may help you to remember that.

• – if you have Gilbert’s syndrome, an inherited condition that can cause elevated bilirubin levels and jaundice (yellow skin and eyes)

• During administration of irinotecan hydrochloride (30–90 minutes) and up to 24 hours after administration you may experience some of the following symptoms: diarrhoea
• sweating
• abdominal pain
• watering eyes
• visual disturbance
• excessive mouth watering

The medical term for these symptoms is “acute cholinergic syndrome” which can be treated (with atropine).

If you have any of these symptoms, immediately tell your doctor who will give you any treatment necessary.

From the day after treatment with irinotecan hydrochloride until next treatment you may experience various symptoms, which may be serious and require immediate treatment and close supervision.

These can be:

Diarrhoea

If your diarrhoea starts more than 24 hours after administration of irinotecan hydrochloride (“delayed diarrhoea”) it may be serious. It is often seen about 5 days after administration. The diarrhoea should be treated immediately and kept under close supervision.

Immediately after the first liquid stools do the following:

• 1. Take any antidiarrhoeal treatment that the doctor has given you, exactly as he/ she has told you. The treatment must not be changed without consulting the doctor. Recommended antidiarrhoeal treatment is loperamide (4 mg for the first intake and then 2 mg every 2 hours, also during the night). This should be continued for at least 12 hours after the last liquid stools. The recommended dosage of loperamide must not be taken for more than 48 hours.

• 2. Drink large amounts of water and rehydration fluids, immediately (i.e. water, soda water, fizzy drinks, soup or oral rehydration therapy).

• 3. Immediately inform your doctor who is supervising the treatment, and tell him/her about the diarrhoea. If you are not able to reach the doctor, contact the hospital unit supervising the irinotecan treatment. It is very important that they are aware of the diarrhoea.

Hospitalisation is recommended for the management of the diarrhoea, in the following cases:

• you have diarrhoea as well as fever (over 38°C)
• you have severe diarrhoea (and vomiting) with excessive loss of water requiring intravenous hydration
• you still have diarrhoea 48 hours after starting the diarrhoea treatment

Note! Do not take any treatment for diarrhoea other than that given to you by your doctor and the fluids described above. Follow the doctor’s instruc­tions. The antidiarrhoeal treatment should not be used preventive, even though you have experienced delayed diarrhoea at previous cycles.

Neutropenia (decrease in some white blood cells)

This medicine can lower your white blood cell count, mainly in the weeks after the medicine is given. This can increase the risk of getting an infection. Be sure to let your doctor or nurse know right away if you have any signs of infection, such as fever (38°C or higher), chills, pain when passing urine, a new cough, or bringing up sputum. Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Blood monitoring

Your doctor will likely test your blood before and during your treatment, to check for effects of the medicine on blood counts or on blood chemistry. Based on the test results, you may need medicines to help treat the effects. Your doctor may also need to reduce or delay your next dose of this medicine, or even stop it altogether. Keep all your appointments for doctor visits and lab tests.

This medicine may lower your platelet count in the weeks after it is given, which can increase your risk of bleeding. Speak with your doctor before taking any medicines or supplements that might affect your body’s ability to stop bleeding, such as aspirin or aspirincontaining medicines, warfarin, or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools.

Nausea and vomiting

You may have nausea and vomiting on the day you receive this medicine or in the first few days after. Your doctor may give you medicine before your treatment to help prevent nausea and vomiting. Your doctor will likely prescribe anti-nausea medicines that you can take at home. Have these medicines on hand for when you need them. Call your doctor if you are unable to take fluids by mouth due to nausea and vomiting.

Acute cholinergic syndrome

This medicine may affect part of your nervous system that controls body secretions, leading to what is known as cholinergic syndrome. Symptoms can include runny nose, increased saliva, excess tears in the eyes, sweating, flushing, abdominal cramps, and diarrhoea. Let your doctor or nurse know right away if you notice any of these symptoms, as there are medicines that can help control them.

Breathing difficulties

If you have any breathing difficulties contact your doctor immediately.

Chronic intestinal inflammation and/or intestinal blockage

Call your doctor if you have pain in your belly and you cannot move your bowels, especially if you also have bloating and loss of appetite.

Irradiation therapy

If you recently received treatment with pelvic or abdominal radiotherapy, you may be at increased risk of developing bone marrow suppression. Please talk to your doctor before starting the Irinotecan Hydrochloride.

Kidney function

Occurrences of kidney dysfunction have been reported, please check with your doctor if you have any kidney problems.

Cardiac disorders

Inform your doctor if you suffer/suffered from heart disease or if you previously received anticancer medicines. Your doctor will monitor you closely and discuss with you how risk factors (for example smoking, high blood pressure and to high fat content) can be reduced.

Vascular disorders

Irinotecan Hydrochloride is rarely associated with blood flow disorders (blood clots in the vessels of your legs and lungs) and it may occur rarely in patients with multiple risks factors.

Others

This medicine may cause sores in the mouth or on the lips, often within the first few weeks after starting treatment. This can cause mouth pain, bleeding, or even trouble eating. Your doctor or nurse can suggest ways to reduce this, such as changing the way you eat or how you brush your teeth. If needed, your doctor can prescribe medicine to help with the pain. For contraception and breast-feeding information, refer to the information provided below under section Contraception, pregnancy, breast-feeding and fertility.

Tell your doctor or dentist that you are on this medicine if you are planning to have surgery or any procedure.

If used in combination with other anticancer medicines for your condition please make sure that you also read the leaflets for the other medicine.

If you have one or more of the symptoms mentioned above, after you have returned home from the hospital, you should immediately contact the doctor or the hospital unit supervising your irinotecan treatment.

Other medicines and Irinotecan Hydrochloride

Irinotecan Hydrochloride can interact with a number of medicines and supplements, which may either raise or lower the level of the medicine in your blood. Tell your doctor or pharmacist if you are using, have recently used or might use any of the following:

• Medicines used to treat seizure (carbamazepine, phenobarbital, phenytoin and fosphenytoin)
• Medicines used to treat fungal infection (ketoconazole, itraconazole, voriconazole and posaconazole)
• Medicines used to treat bacterial infection (clarithromycine, erythromycin and telithromycine)
• 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 blood thinner such as Warfarin)
• Medicines used to relax muscles used during general anaesthesia and surgery (suxamethonium)
• 5-fluorouracil/fo­linic acid
• Bevacizumab (a blood vessel growth inhibitor)
• Cetuximab (an EGF receptor inhibitor)

Tell your doctor, pharmacist or nurse before being given Irinotecan Hydrochloride if you are already having, or have recently had chemotherapy (and radiotherapy).

Don't start or stop taking any medicines while you are on Irinotecan Hydrochloride without talking with your doctor first.

This medicine can cause serious diarrhoea. Try to avoid laxatives and stool softeners while taking this medicine.

There may be more medicines that interact with Irinotecan Hydrochloride. Check with your doctor, pharmacist or nurse about your other medicines, herbs, and supplements, and whether alcohol can cause problems with this medicine.

Contraception, pregnancy, breast-feeding and fertility

Contraception

If you are a woman of childbearing age, then you have to use effective contraception during and up to 6 months after stopping treatment.

As a man, you have to use effective contraception during and up to 3 months after stopping treatment. It is important to check with your doctor about what kinds of birth control can be used with this medicine.

Pregnancy

This medicine may cause problems with the foetus if taken at the time of conception or during pregnancy. Before initiating treatment, your doctor will ensure that you are not pregnant.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Breast-feeding

Irinotecan and its metabolite were measured in human milk. Breast-feeding should be discontinued for the duration of your treatment with this medicine.

If you are breast-feeding, ask your doctor or pharmacist for advice before taking this medicine.

Fertility

No studies have been done, nevertheless, this medicine may affect fertility. Prior to taking this medicine talk with your doctor about the possible risk with this medicine and the options that may preserve your ability to have children.

Driving and using machines

You may notice that you are dizzy and/or have trouble with your vision in the first 24 hours or so after you take this medicine. Do not drive or operate machinery if you have this side effect.

Irinotecan Hydrochloride 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 tell your doctor before receiving this medicine if you (or your child) have 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 diarrhoea.

This medicine contains 45 mg sorbitol in each ml which is equivalent to 90 mg/2 ml, 225 mg/5 ml and 675 mg/15 ml.

3. how to take irinotecan hydrochloride

Always use this medicine exactly as your doctor has told you. Check with your doctor is you are not sure.

For adults only.

Irinotecan will be given as an infusion into your veins over a period of 30–90 minutes.

The amount of infusion you are given will depend on your age, height, weight and general medical condition. Your doctor will calculate your body surface area in square metres (m2) from your height and weight. The dosage will also depend on any other treatment you may have received for your cancer.

• if you have previously been treated with 5-fluorouracil you will normally be treated with irinotecan alone starting with a dose of 350 mg/m2 every 3 weeks.
• if you have not had previous chemotherapy you will normally receive 180 mg/m2 irinotecan every two weeks. This will be followed by folinic acid and 5-fluorouracil.

If you receive irinotecan in combination with cetuximab, irinotecan must not be administered earlier than one hour after the end of the cetuximab infusion.

Please follow the advice of your doctor regarding your current treatment.

These dosages may be adjusted by your doctor depending on your condition and any side effects you may have.

If you use more Irinotecan Hydrochloride than you should

In case you were given a higher dosage of irinotecan than required the occurring side effects may be more severe. You will get maximum supportive care to prevent dehydration due to diarrhoea and to treat any infectious complication.

If you think you have been administered an overdose please contact your doctor.

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

If you forget to use Irinotecan Hydrochloride

Call your doctor for instructions if you miss an appointment for Irinotecan Hydrochloride injection.

If you have any further questions on 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 effect could be serious. You must immediately contact your doctor if you experience any of those following serious side effects (see section 2).

Some of these side effects must be treated immediately. These are:

• Allergic reaction: hives; breathing difficulties; swelling of your face, lips, tongue, or throat.
• Diarrhoea (see section 2)
• Early diarrhoea: Occurring within 24 hours of receiving this medicine, accompanied by symptoms runny nose, increased salivation, watery eyes, sweating, flushing, abdominal cramping. (This can occur while the medicine is being administered. If so, alert your healthcare professional promptly. Medication can be given to stop and/or lessen this early side effect).
• Late diarrhoea: Occurring greater than 24 hours of receiving this medicine. Because of concerns of dehydration and electrolyte imbalances with diarrhoea it is important to be in contact with health care professionals for monitoring, and for medication and diet modifications advice.

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

Symptoms	Frequency* of occurrence in Monotherapy	Frequencyt of occurrence in Combination Therapy
Abnormally low number of white blood cells which could put you at increased risk for infection	Very common	Very common
Low number of red blood cells causing tiredness and shortness of breath	Very common	Very common
Decreased appetite	Very common	Very common
Cholinergic syndrome (see Take special care with Irinotecan hydrochloride)	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
Inflammation of mucous membranes	Very common	Very common
Fever	Very common	Common
Feeling weak and having no energy	Very common	Very common
Low number of platelets (blood cells that help with clotting) which may cause bruising or bleeding	Common	Very common
Abnormal liver function test values	Common	Very common
Infection	Common	Common
Low number of white blood cells with fever	Common	Common
Difficulty in passing stools	Common	Common
Abnormal kidney function test values	Common	Not reported

• * Very common: may affect more than 1 in 10 people j Common: may affect up to 1 in 10 people

Not known: frequency cannot be estimated from the available data

• Severe, persistent or bloody diarrhoea (which may be associated with stomach pain or fever) caused by bacteria called (Clostridium difficile)
• Blood infection
• Dehydration (due to diarrhoea and vomiting)
• Dizziness, rapid heart beat and pale skin (a condition called hypovolaemia)
• Allergic reaction
• Temporary speech disorders during or shortly after treatment
• Pins and needles
• High blood pressure (during or after infusion)
• Heart problems*
• Lung disease causing wheezing and shortness of breath (see section 2)
• Hiccups
• Intestinal blockage
• Enlarged colon
• Bleeding from the bowels
• Inflammation of the large intestine
• Abnormal lab test results
• 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 mostly related with diarrhoea and vomiting
• Muscle cramps
• Kidney problems*
• Low blood pressure*
• Fungal infections
• Viral infections

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

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side affects you can help provide more information on the safety of this medicine.

5. how to store irinotecan hydrochloride

• Keep this medicine out of the sight and reach of children.
• For single use only
• Do not use this medicine after the expiry date which is stated on the carton and the vial after EXP. The first two numbers indicate the month; the last four numbers indicate the year. The expiry date refers to the last date of that month.
• Keep the vials in outer carton in order to protect from light.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other informationwhat irinotecan hydrochloride contains the active substance irinotecan hydrochloride, trihydrate 20 mg/ml equivalent to 17.33 mg/ml irinotecan.

One vial of 2 ml contains 40 mg of irinotecan hydrochloride trihydrate (40 mg/2 ml).

One vial of 5 ml contains 100 mg of irinotecan hydrochloride trihydrate (100 mg/5 ml).

One vial of 15 ml contains 300 mg of irinotecan hydrochloride trihydrate (300 mg/15 ml).

• The other ingredients are: Sorbitol E420 (see section 2), lactic acid, sodium hydroxide, hydrochloric acid and water for injections.

What Irinotecan Hydrochloride looks like and contents of the pack

Irinotecan Hydrochloride 20 mg/ml concentrate for solution for infusion is a Pale yellow clear solution.

Vials contain 40 mg/2ml, 100 mg/5ml or 300 mg/15ml of solution

Irinotecan Hydrochloride 40mg/2ml concentrate for solution for infusion:

It comprises of 2R Type-I Tubular amber glass vial with 13mm neck stoppered with 13mm grey bromo butyl rubber stoppers and sealed with aluminium seals having red colour polypropylene disc.

Irinotecan Hydrochloride 100mg/5ml concentrate for solution for infusion:

It comprises of 6R Type-I Tubular amber glass vial with 20 mm neck stoppered with 20mm grey bromo butyl rubber stoppers and sealed with aluminium seals having sky blue colour polypropylene disc.

Irinotecan Hydrochloride 300mg/15ml concentrate for solution for infusion:

It comprises of 20R Type-I Tubular amber glass vial with 20 mm neck stoppered with 20mm grey bromo butyl rubber stoppers and sealed with aluminium seals having sky blue colour polypropylene disc.

Pack sizes:

1 × 2 ml vial

1 × 5 ml vial

1 × 15 ml vial

Marketing Authorisation Holder

Milpharm Limited

Ares Block

Odyssey Business Park

West End Road

Ruislip HA4 6QD

United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far,

Birzebbugia, BBG 3000, Malta

Or

Milpharm Limited

Ares Block, Odyssey Business Park, West End Road,

Ruislip, HA4 6QD, United Kingdom

Or

Generis Farmaceutica, S.A.,

Rua Joao de Deus, n.o 19, Venda Nova, 2700–487

Amadora, Portugal

This leaflet was last revised in 12/2021.

The following information is intended for healthcare professionals only

Instructions for use/handling

Like all anti-neoplastic substances, irinotecan must be prepared and handled carefully. The use of protective glasses, mask and gloves is required.

If irinotecan comes into contact with your skin, wash it off immediately and thoroughly with soap and water. If irinotecan comes into contact with your mucous membranes, wash it off immediately and thoroughly with water.

As with all injectable drugs, irinotecan must be prepared under aseptic conditions.

If a clouding or condensation is visible in the vial or after dilution of the concentrate, the medicine may not be used and must be disposed of.

Preparation of the intravenous infusion

As with any other injectable drugs, irinotecan infusion must be prepared aseptically. If you observe any precipitate in the vial or solution for infusion, discard the product according to standard procedures for cytotoxic agents.

Aseptically withdraw the required amount of irinotecan concentrate from the vial with a calibrated syringe and inject into a 250 ml infusion bag or bottle containing either 0.9% (w/v) sodium chloride solution or 5% (w/v) glucose infusion solution. Mix the solution for infusion in the infusion bag or bottle thoroughly by manual rotation.

Do not mix with other medicines.

Disposal

All materials used for dilution and administration should be disposed of according to local procedures applicable to the discarding of cytotoxic agents.