Irinotecan Mylan Generics

Package leaflet: Information for the user

Irinotecan Mylan Generics

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

Contents of this leaflet:

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

1. What Irinotecan Mylan Generics is and what it is used for

IRINOTECAN is an anticancer medicine containing the active substance irinotecan hydrochloride trihydrate.
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 as monotherapy in patients with metastatic carcinoma of the colon or rectum
whose disease has recurred or progressed following initial fluorouracil-based therapy.

2. What you need to know before you are given Irinotecan Mylan Generics

Do not receive Irinotecan Mylan Generics if:

• you have a chronic inflammatory bowel disease and/or intestinal obstruction
• you are allergic to irinotecan hydrochloride trihydrate or to any of the other ingredients of this medicine (listed in section 6 “What Irinotecan Mylan Generics contains”)
• you are breastfeeding (see section 2)
• your bilirubin level is more than 3 times the upper limit of the normal range
• you have severe bone marrow failure
• your general health status is poor (determined by WHO performance status greater than 2)
• you are taking or have recently taken the herbal remedy St. John’s Wort (a herbal product containing hypericum)
• you are due to receive or have recently received live attenuated vaccines (vaccines against yellow fever, varicella, herpes zoster, mumps, measles, rubella, tuberculosis, rotavirus, influenza), and during the 6 months following the end of chemotherapy.

If Irinotecan is administered to you in combination with other medicines, please read the package leaflet of the other medicines for additional contraindications.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Irinotecan.
Exercise particular caution with Irinotecan. The use of Irinotecan must be restricted to specialized units experienced in administering cytotoxic chemotherapy and must only be administered under the supervision of a physician qualified in the use of anticancer chemotherapy.
Diarrhea
Irinotecan may cause diarrhea, which in some cases can be severe. It may begin a few hours or a few days after drug infusion. If untreated, it may lead to dehydration and serious chemical imbalances, which can be life-threatening. Your doctor will prescribe a medicine to help prevent or control this side effect. Make sure you have this medicine immediately available so you can take it when needed.

• Take the medicine as prescribed at the first sign of loose or frequent bowel movements.
• Drink plenty of water and/or saline drinks (sparkling water, carbonated beverages, or broth).
• Inform your doctor or nurse if you still have diarrhea, especially if it lasts longer than 24 hours, or if you experience dizziness, lightheadedness, or fainting.

Neutropenia (decrease in a certain type of white blood cells)
This medicine may reduce the white blood cell count, mainly in the weeks following administration. This may increase the risk of developing an infection. Make sure to inform your doctor or nurse immediately if you notice any signs of infection, such as fever (38°C or higher), chills, pain during urination, new cough, or sputum production. Avoid close contact with people who are ill or have infections. Inform your doctor immediately if you develop signs of infection.
Blood monitoring
Your doctor will likely perform blood tests before and during treatment to monitor the effects of the medicine on your blood count or blood composition. Based on test results, you may need to take medicines to treat any effects. Your doctor may also need to reduce or delay the next dose of this medicine, or even stop it completely. Do not miss your scheduled medical visits and laboratory tests.
This medicine may reduce platelet count in the weeks following administration, increasing the risk of bleeding. Talk to your doctor before taking any medicine or supplement that may affect your body’s ability to stop bleeding, such as aspirin or medicines containing aspirin, warfarin, or vitamin E. Inform your doctor immediately if you notice unusual bruising or bleeding, such as nosebleeds, bleeding gums when brushing your teeth, or black, tarry stools.
Nausea and vomiting
You may experience nausea and vomiting on the day of administration or in the first few days afterward. Your doctor may prescribe medicines before treatment to prevent nausea and vomiting. Your doctor will likely prescribe anti-nausea medicines for you to take home. Keep these medicines 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 body secretions, causing a condition known as cholinergic syndrome. Symptoms may include runny nose, excessive salivation, excessive tearing, sweating, flushing, abdominal cramps, and diarrhea. Inform your doctor or nurse immediately if you notice any of these symptoms, as medicines are available to help control them.
Pulmonary disorders
Rarely, people taking this medicine have experienced serious lung problems. Inform your doctor immediately if you develop a new or worsening cough, breathing difficulties, or fever. Your doctor may discontinue treatment to manage this issue.
This medicine may increase the risk of developing serious 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, or swelling, pain, redness, or warmth in one arm or leg.
Chronic intestinal inflammation and/or intestinal blockage
Consult your doctor if you experience abdominal pain and constipation, especially if you also have bloating and loss of appetite.
Radiation therapy
If you have recently received pelvic or abdominal radiotherapy, the risk of developing bone marrow suppression may be increased. Talk to your doctor before starting Irinotecan.
Renal function
Kidney dysfunction has been reported.
Cardiac disorders
Inform your doctor if you have or have had heart disease or if you have previously received anticancer medicines. Your doctor will monitor you closely 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 legs and lungs), and these may rarely occur in patients with multiple risk factors.
Other
This medicine may cause mouth or lip ulcers, often in the first few weeks after starting treatment. This may cause mouth pain, bleeding, or even feeding difficulties. Your doctor or nurse may suggest ways to reduce this problem, such as changing how you eat or brush your teeth. If needed, your doctor may prescribe medicines to relieve pain.
Inform your doctor or dentist that you are taking this medicine if you are planning surgery or any other procedure.
If used in combination with other anticancer medicines to treat your condition, make sure you have also read the package leaflets of the other medicines.
If your doctor has told you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.
Children and adolescents
Not applicable
Other medicines and Irinotecan Mylan Generics
Irinotecan may interact with a number of medicines and supplements that 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 epilepsy (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 the body’s immune system to prevent transplant rejection (cyclosporine and tacrolimus)
• Medicines used to treat cancer (regorafenib, crizotinib, and idelalisib)
• Vitamin K antagonists (common anticoagulants such as warfarin)
• Medicines used to relax muscles during surgery under general anesthesia (succinylcholine)
• 5-fluorouracil/folinic acid
• Bevacizumab (an inhibitor of blood vessel growth)
• Cetuximab (an EGFR inhibitor)

Do not start or stop taking any medicine while undergoing treatment with Irinotecan without first consulting your doctor.
This medicine may cause severe diarrhea. Try to avoid laxatives and stool softeners while taking this medicine.
Other medicines have also been shown to interact with Irinotecan. Check with your doctor, pharmacist, or nurse about other medicines, herbal remedies, and supplements you are taking, and whether alcohol could cause problems with this medicine.
Pregnancy, breastfeeding, and fertility
Women of childbearing potential / Contraception in males and females
Women of childbearing potential and men must use an effective method of contraception during treatment and for one month and three months, respectively, after the end of treatment.
Pregnancy
This medicine may harm the unborn baby if taken at the time of conception or during pregnancy. Men and women taking this medicine must use a reliable method of birth control during treatment. It is important to discuss with your doctor which types of birth control methods can be used with this medicine. In pregnant women, treatment with this medicine should only be used if the potential benefit to the mother outweighs the risks to the fetus.
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Breastfeeding
No studies have been conducted; however, this medicine may pass into breast milk and affect the baby. Breastfeeding must be discontinued for the entire duration of treatment with this medicine.
If you are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Fertility
No studies have been conducted; however, this medicine may affect fertility. Talk to your doctor about the possible risks with this medicine and options to improve the chances of having children in the future.
Driving and using machines
You may experience dizziness and/or visual disturbances within approximately the first 24 hours after taking this medicine. Do not drive or operate machinery if you experience any adverse effects.
Irinotecan Mylan Generics contains sorbitol and sodium.
Sorbitol is a source of fructose. If your doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic disorder, you (or your child) must not take this medicine. Patients with hereditary fructose intolerance cannot metabolize fructose, and its accumulation may cause serious side effects.
Before taking this medicine, inform your doctor if you (or your child) have hereditary fructose intolerance or if your child feels unwell, vomits, or has unpleasant reactions such as bloating, stomach cramps, or diarrhea after consuming sweet foods or drinks.
This medicinal product contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially "sodium-free."

3. How Irinotecan Mylan Generics will be administered to you

Use this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor.
IRINOTECAN will be administered by healthcare professionals.
Your doctor may request a DNA test before administering the first dose of IRINOTECAN.
Some people are genetically more predisposed to developing certain side effects of the medicine.
The amount of IRINOTECAN to be infused depends on many factors, including height and weight, general medical condition, other health problems, and the type of cancer or condition being treated. Your doctor will determine the dose and schedule.
IRINOTECAN is injected into a vein intravenously (IV). This injection will be performed in a clinic or hospital. IRINOTECAN must be administered slowly, and the intravenous infusion may take up to 90 minutes.
You may receive other medications to prevent nausea, vomiting, diarrhea, and other side effects while you are receiving IRINOTECAN. You may need to continue taking these medicines for at least one day after the IRINOTECAN injection.
Inform healthcare providers if you experience pain, burning, or swelling around the injection needle when IRINOTECAN is being administered. 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 during the IRINOTECAN infusion, inform your doctor immediately.
There are currently several recommended treatment regimens for IRINOTECAN. It is usually administered once every 3 weeks (IRINOTECAN as monotherapy) or once every 2 weeks (IRINOTECAN administered in combination with the chemotherapeutic agent 5FU/FA). The dose will depend on a number of factors, including the treatment regimen, body size, age, general health status, blood counts, proper liver function, whether you have received prior radiotherapy to the abdomen/pelvis, and whether you experience side effects such as diarrhea.
Only your doctor can assess the duration of treatment.
If you use more IRINOTECAN than you should
Seek emergency medical assistance. Symptoms of overdose may include some of the serious side effects listed in this leaflet.
If you forget to use IRINOTECAN
Ask your doctor for instructions if you miss a scheduled administration session of IRINOTECAN.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some side effects may be serious. You must contact your doctor immediately if you experience any of the following serious side effects (see section 2).
Seek emergency medical help if you notice any of these 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 administration of the medicine, accompanied by symptoms such as runny nose, increased salivation, tearing, sweating, flushing, abdominal cramps. (These may occur during administration of the medicine; if so, inform healthcare personnel immediately. Medicines can be given to stop and/or reduce these initial side effects.)
• Delayed diarrhoea: occurs more than 24 hours after administration of the medicine. Because of problems related to dehydration and electrolyte imbalances caused by diarrhoea, it is important to contact healthcare providers for monitoring and advice on medications and dietary adjustments.

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
Not known: frequency cannot be estimated from the available data

• Severe, persistent or bloody diarrhoea which may be associated with stomach pain or fever due to the bacterium Clostridium difficile
• Blood infection
• Fungal infections
• Viral infections
• Dehydration (due to diarrhoea and vomiting)
• Dizziness, rapid heartbeat and pale skin (a condition called hypovolemia)
• Allergic reaction
• Transient speech disturbances during or immediately after treatment
• Tingling
• High blood pressure (during or after infusion)
• Heart problems*
• Lung disease causing wheezing and shortness of breath (see section 2)
• Hiccups
• Intestinal blockage
• Enlarged colon
• Intestinal bleeding
• Inflammation of the large intestine
• Abnormal laboratory test results
• Intestinal perforation
• Fatty liver
• Skin reactions
• Reactions at the infusion site
• Low level of potassium in the blood
• Low level of sodium in the blood mainly related to diarrhoea and vomiting
• Muscle cramps
• Kidney problems*
• Low blood pressure*

* Non-frequent 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 experience any adverse reactions, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report adverse reactions directly via the website http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Irinotecan Mylan Generics

Store below 25°C. Do not freeze.
Do not use this medicinal product after the expiry date stated on the carton or vial after
EXP. The expiry date refers to the last day of that month.
Keep the vial in the outer packaging to protect the medicinal product from light.
After dilution in 0.9% sodium chloride solution (9 mg/ml) or 5% glucose solution (50 mg/ml), chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C and at 25°C, protected from light.
From a microbiological point of view, unless the method of opening/dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the times and conditions of in-use storage are under the responsibility of the user.
Do not use the medicinal product if precipitation is observed in the vials or after dilution; the product must be disposed of according to standard procedures for cytotoxic agents.
Do not dispose of any medicinal product via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Pack contents and other information

What Irinotecan Mylan Generics contains

• The active substance is irinotecan hydrochloride trihydrate. Each 2 ml vial contains 40 mg of irinotecan hydrochloride trihydrate, equivalent to 34.66 mg of irinotecan. Each 5 ml vial contains 100 mg of irinotecan hydrochloride trihydrate, equivalent to 86.65 mg of irinotecan. Each 15 ml vial contains 300 mg of irinotecan hydrochloride trihydrate, equivalent to 259.95 mg of irinotecan. Each 25 ml vial contains 500 mg of irinotecan hydrochloride trihydrate, equivalent to 433.25 mg of irinotecan.

1 ml of concentrate for solution for infusion contains 20 mg of irinotecan hydrochloride trihydrate
equivalent to 17.33 mg of irinotecan.
The other components are: sorbitol E420, lactic acid, sodium hydroxide (to adjust pH) and water for
injections.

Description of the appearance of Irinotecan Mylan Generics and pack contents
This medicinal product is a concentrate for solution for infusion. It is a clear solution.
Vials (amber glass type I) of 2 ml, 5 ml, 15 ml or 25 ml of solution with a chlorobutyl rubber closure and a cap (flip-off type). Packs containing 1, 5, 10 and 20 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Mylan SpA
Via Vittor Pisani, 20
20124 Milan
Italy

Manufacturer and responsible for batch release
GP Pharm
Pol. Ind. Els Vinyets-Els Fogars, Sector 2 Carretera Comarcal C-244, Km. 22-08777 Sant Quinti de
Mediona
(Barcelona) Spain
Mylan S.A.S
117 Allée des Parcs
69800 Saint-Priest
France
Vianex S.A,
Plant C, 16th Km. Marathonos Ave.,
15351 Pallini Attiki, Athens,
Greece
Mylan Spa
Viale dell’Innovazione 3
20126 Milan, Italy

This leaflet was last updated on
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The following information is intended exclusively for medical or healthcare personnel:

Instructions for use/handling, guidance for preparation and disposal for use with Irinotecan
Mylan Generics concentrate for solution for infusion

USE/HANDLING
As with other antineoplastic drugs, Irinotecan Mylan Generics must be prepared and handled with care. The use of goggles, mask, and gloves is required.
If the Irinotecan solution or the prepared infusion solution comes into contact with the skin, wash IMMEDIATELY and thoroughly with soap and water. If the Irinotecan solution or the prepared infusion solution comes into contact with mucous membranes, rinse IMMEDIATELY with water.

Preparation of intravenous solution.
As with all injectable drugs, the irinotecan solution must be prepared under aseptic conditions.
If precipitation is observed in the vials or after dilution, the product must be discarded following standard procedures for cytotoxic drugs.
Do not use Irinotecan Mylan Generics if you notice any visible signs of deterioration.

Under aseptic conditions, withdraw the required amount of Irinotecan solution from the vial using a graduated syringe and inject it into an infusion bag or bottle containing 250 ml of 0.9% sodium chloride solution or 5% glucose solution. The solution should then be thoroughly mixed by gentle manual rotation.

After dilution in 0.9% sodium chloride solution (9 mg/mL) or 5% glucose solution (50 mg/mL), chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C and at 25°C, protected from light.

From a microbiological standpoint, unless the method of opening/dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the duration and conditions of in-use storage are under the responsibility of the user.

The solution of Irinotecan Mylan Generics must be administered via central or peripheral vein.
Irinotecan Mylan Generics must not be administered as an intravenous bolus or as an intravenous infusion over less than 30 minutes or more than 90 minutes.

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