Gemcitabine Aurobindo Pharma Italia

Package leaflet: Information for the user

Gemcitabine Aurobindo Pharma Italia 40 mg/ml concentrate for solution for infusion

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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Gemcitabina Aurobindo Pharma Italia is and what it is used for

Gemcitabina Aurobindo Pharma Italia belongs to a group of medicines called "cytotoxic agents". These
medicines inhibit cell division, including that of cancer cells.
Gemcitabina Aurobindo Pharma Italia may be administered alone or in combination with other anticancer
drugs, depending on the type of cancer.
Gemcitabina Aurobindo Pharma Italia is used to treat the following cancers:

• Non-small cell lung cancer (NSCLC), either alone or in combination with cisplatin.
• Pancreatic cancer.
• Breast cancer, in combination with paclitaxel.
• Ovarian cancer, in combination with carboplatin.
• Bladder cancer, in combination with cisplatin.

2. What you need to know before using Gemcitabine Aurobindo Pharma Italia

Do not use Gemcitabine Aurobindo Pharma Italia:

• if you are allergic to gemcitabine or to any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding.

Warnings and precautions
Before the first infusion, blood tests will be performed to assess adequate liver and kidney function for treatment with this medicine. Before each infusion, blood tests will be carried out to check that there are enough blood cells to receive Gemcitabine Aurobindo Pharma Italia. Your doctor may decide to adjust the dose or delay treatment depending on your general condition and if blood cell counts are too low.
Periodic blood tests will be performed to monitor your liver and kidney function.
Contact your doctor, nurse, or hospital before using Gemcitabine Aurobindo Pharma Italia.
If you have or have previously had liver, heart, vascular diseases or kidney problems, discuss this with your doctor or hospital pharmacist, as you may not be able to take Gemcitabine Aurobindo Pharma Italia.
If you have recently undergone or are about to undergo radiotherapy, inform your doctor, as early or delayed radiation reactions may occur with Gemcitabine Aurobindo Pharma Italia.
If you have recently been vaccinated, inform your doctor, as this may cause adverse effects when used with Gemcitabine Aurobindo Pharma Italia.
If during treatment with this medicine you experience symptoms such as headache, confusion, seizures or changes in vision, contact your doctor immediately. This could be a very rare nervous system adverse event called reversible posterior encephalopathy syndrome.
If you develop breathing difficulties, severe weakness or look pale, inform your doctor, as these may be signs of kidney failure or lung problems.
If you develop generalized swelling, shortness of breath or weight gain, inform your doctor, as these may indicate leakage of fluids from blood vessels into tissues.

Children and adolescents
The use of this medicine is not recommended in children under 18 years of age, as data on safety and efficacy are insufficient.

Other medicines and Gemcitabine Aurobindo Pharma Italia
Inform your doctor or hospital pharmacist if you are taking, have recently taken or might take any other medicines, including vaccines and over-the-counter medicines; or if you have recently undergone or are about to undergo radiotherapy.

Pregnancy, breastfeeding and fertility

Pregnancy
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. The use of Gemcitabine Aurobindo Pharma Italia during pregnancy should be avoided. Your doctor will inform you about the potential risks associated with taking Gemcitabine Aurobindo Pharma Italia during pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding.
Breastfeeding must be discontinued during treatment with Gemcitabine Aurobindo Pharma Italia.

Fertility
Men treated with Gemcitabine Aurobindo Pharma Italia should be advised not to father a child during treatment and for 6 months after treatment ends. If you wish to father a child during treatment or within 6 months after treatment, consult your doctor or pharmacist. It is recommended to seek information about sperm preservation methods before starting therapy.

Driving and using machines
Gemcitabine Aurobindo Pharma Italia may cause drowsiness.
You must not drive a vehicle or operate machinery until you are certain that treatment with Gemcitabine Aurobindo Pharma Italia does not affect your level of attention.

3. How to use Gemcitabina Aurobindo Pharma Italia

The recommended dose of Gemcitabina Aurobindo Pharma Italia is 1000–1250 mg per square metre of body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor must use this body surface area to calculate the correct dose for you. This dosage may be adjusted or the treatment may be delayed depending on your blood test results and your general condition.

The frequency with which you receive Gemcitabina Aurobindo Pharma Italia infusion depends on the type of cancer for which you are being treated.

A hospital pharmacist or doctor must dilute the Gemcitabina Aurobindo Pharma Italia concentrate before it is administered to you.

You will always receive Gemcitabina Aurobindo Pharma Italia as an intravenous infusion. The infusion will last approximately 30 minutes.

The use of this medicine is not recommended in children under 18 years of age.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you notice any of the following:

• Bleeding from the gums, nose or mouth, or any bleeding that tends not to stop, red or slightly pink urine, unexpected bruising (because you may have fewer platelets than normal, which is very common).
• Tiredness, feeling faint, shortness of breath or looking pale (because you may have less haemoglobin than normal, which is very common).
• Allergic reactions: if you develop mild to moderate skin rashes (very common); itching (common); or fever (very common).
• Body temperature of 38°C or higher, sweating or other signs of infection (because you may have fewer white blood cells than normal accompanied by fever, also known as febrile neutropenia) (common).
• Pain, redness, swelling or sores in the mouth (stomatitis) (common).
• Irregular heartbeat (arrhythmia) (uncommon).
• Extreme tiredness and weakness, purpura or small areas of bleeding under the skin (bruising), acute kidney failure (limited or no urine output), and signs of infection (haemolytic uraemic syndrome). This can be fatal (uncommon).
• Breathing difficulties (immediately after infusion with Gemcitabine Aurobindo Pharma Italia, mild breathing difficulty is very common and passes quickly; however, more serious lung problems are uncommon or rare).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity/allergic reaction with severe skin rash including red, itchy skin, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and feeling faint (anaphylactic reaction) (very rare).
• Headache with changes in vision, confusion, seizures or convulsions (reversible posterior encephalopathy syndrome) (very rare).
• Severe rash with itching, blisters or skin cracking, often accompanied by flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Extreme tiredness and weakness, purpura or small areas of bleeding under the skin (bruising), acute kidney failure (low or no urine output), and signs of infection. These may be features of thrombotic microangiopathy (clots forming in small blood vessels) and haemolytic uraemic syndrome, which can be fatal.

Other side effects with Gemcitabine Aurobindo Pharma Italia may include:
Very common side effects (may affect more than 1 in 10 people)
Low white blood cell count
Breathing difficulties
Vomiting
Nausea
Hair loss
Liver problems: detected through abnormalities in blood tests
Abnormalities in urine test: protein in urine
Flu-like symptoms, including fever
Swelling of the ankles, hands, feet and face (oedema)
Low haemoglobin levels (anaemia)

Common side effects (may affect up to 1 in 10 people)
Loss of appetite (anorexia)
Headache
Insomnia
Drowsiness
Cough
Runny nose
Constipation
Diarrhoea
Sweating
Muscle pain
Back pain
Fever
Weakness
Chills
Infections

Uncommon side effects (may affect up to 1 in 100 people)
Scarring of air sacs in the lung (interstitial pneumonia)
Wheezing (spasm of the airways)
Scarring of the lungs (abnormal chest X-ray/scan)
Heart failure
Kidney failure
Severe liver damage, including liver failure which can be life-threatening
Stroke

Rare side effects (may affect up to 1 in 1,000 people)
Low blood pressure
Skin peeling, ulceration or blistering rash
Skin shedding and severe blister formation on the skin
Reactions at the injection site
Severe lung inflammation causing respiratory failure (adult respiratory distress syndrome)
Skin rash resembling a severe sunburn appearing on skin previously exposed to radiotherapy (radiation recall reaction)
Fluid in the lungs
Scarring of lung alveoli secondary to radiotherapy (radiation toxicity)
Gangrene of the fingers or toes
Inflammation of blood vessels (peripheral vasculitis)

Very rare side effects (may affect up to 1 in 10,000 people)
Increased platelet count
Inflammation of the lining of the large intestine due to reduced blood supply (ischaemic colitis)
Low haemoglobin levels (anaemia), low white blood cell count and low platelet count will be detected by a blood test
Thrombotic microangiopathy: clots forming in small blood vessels

Side effects not known (frequency cannot be estimated from available data)
Sepsis: when bacteria and their toxins circulate in the blood and start damaging organs
Pseudocellulitis: skin redness with swelling

You may experience one or more of these symptoms and/or conditions. Contact your doctor immediately if you start experiencing any of these side effects.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Gemcitabina Aurobindo Pharma Italia

Keep this medicine out of the sight and reach of children.
Sealed container
Store in a refrigerator (2 °C – 8 °C).
After first opening
Chemical and physical stability during use has been demonstrated for 28 days at 25°C.
From a microbiological standpoint, the product should be used immediately unless the method of opening excludes the risk of microbial contamination. Otherwise, the in-use storage times and conditions prior to use are the responsibility of the user.
Infusion solution
Chemical and physical stability during use after dilution in 0.9% sodium chloride solution at final concentrations in the range of 2–2.5 mg/ml (2.0 mg/ml, 12 mg/ml, and 25 mg/ml) has been demonstrated for 28 days between 2°C and 8°C and at approximately 25°C. Diluted solutions are stable when packaged in PVC or PE infusion bags.
From a microbiological standpoint, the infusion solution should be used immediately. Otherwise, in-use storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2–8°C, unless the dilution was carried out under controlled and validated aseptic conditions.
Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
Do not use this medicine if particulate matter is observed.

6. Package contents and other information

What Gemcitabina Aurobindo Pharma Italia contains

• The active substance is gemcitabine (as gemcitabine hydrochloride). Each ml of concentrate for solution for infusion contains 40 mg of gemcitabine (as gemcitabine hydrochloride). Each 5 ml vial contains 200 mg of gemcitabine (as gemcitabine hydrochloride). Each 25 ml vial contains 1 g of gemcitabine (as gemcitabine hydrochloride). Each 50 ml vial contains 2 g of gemcitabine (as gemcitabine hydrochloride).
• The other components are hydrochloric acid (E-507) for pH adjustment, water for injections.

Description of the appearance of Gemcitabina Aurobindo Pharma Italia and contents of the pack
Gemcitabina Aurobindo Pharma Italia concentrate for solution for infusion is a clear, colourless or pale yellow solution.
Gemcitabina Aurobindo Pharma Italia is contained in a clear glass vial closed with a rubber stopper and sealed with an aluminium cap with a polypropylene disc. Each vial will be packaged with or without a protective plastic overwrap.
Pack sizes:
1 vial of 5 ml
1 vial of 25 ml
1 vial of 50 ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront,
Floriana FRN 1914, Malta

Manufacturer
Generis Farmacêutica, S.A.
Rua João de Deus, n 19, Venda Nova,
2700-487 Amadora,
Portugal
APL Swift Services (Malta) Ltd.
HF26, Hal Far Industrial Estate, Hal Far,
Birzebbugia BBG 3000,
Malta.

This medicinal product is authorised in the European Economic Area Member States under the following names:
Belgium Gemcitabine AB 40 mg/ml, concentrate for solution for infusion
Italy Gemcitabina Aurobindo Pharma Italia
Luxembourg Gemcitabine Aurobindo 40 mg/ml, concentrate for solution for infusion
Netherlands Gemcitabine Aurobindo 40 mg/ml, concentrate for solution for infusion
Portugal Gemcitabina Aurovitas
Spain Gemcitabina Aurovitas Spain 200 mg/1000 mg/2000 mg concentrate for solution for infusion

The following information is intended for healthcare professionals only:

Instructions for use

Gemcitabine Aurobindo Pharma Italia 40 mg/ml concentrate for solution for infusion

Cytotoxic
Handling
Standard safety precautions for cytostatic agents must be observed when preparing and disposing of the infusion solution. Pregnant personnel must not handle this medicinal product.
Preparation of the infusion solution must be carried out in a safe environment, and protective clothing and gloves must be worn. If a safe environment is not available, protective equipment must include a mask and safety goggles.
If the solution comes into contact with the eyes, it may cause severe irritation. The eyes must be immediately and thoroughly rinsed with water. If irritation persists, a physician must be consulted. If the solution contacts the skin, wash thoroughly with water.

Instructions for dilution
The only approved diluent for dilution of Gemcitabine Aurobindo Pharma Italia concentrate for solution for infusion is sodium chloride 9 mg/ml (0.9%) solution for injection (without preservatives).

• Use aseptic technique during dilution of gemcitabine for intravenous infusion.
• The diluted solution is a clear, colourless or pale yellow solution.
• Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. Do not administer if particulate matter is observed.
• Unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.

Storage conditions
After first opening
Chemical and physical in-use stability has been demonstrated for 28 days at 25°C. From a microbiological standpoint, the product should be used immediately unless the method of opening precludes the risk of microbial contamination. Otherwise, the in-use storage times and conditions prior to use are the responsibility of the user.

Infusion solution
Chemical and physical in-use stability after dilution in 0.9% sodium chloride solution at final concentrations in the range 2–2.5 mg/ml (2.0 mg/ml, 12 mg/ml and 25 mg/ml) has been demonstrated for 28 days between 2°C and 8°C and at approximately 25°C. The pH of the diluted solution is in the range 2–3 and osmolarity is approximately 285 mOsm/kg. Diluted solutions are stable when stored in PVC or PE infusion bags.
From a microbiological standpoint, the infusion solution should be used immediately. Otherwise, in-use storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.