PACKAGE LEAFLET: INFORMATION FOR THE USER

Gemcitabine 200 mg powder for solution for infusion Gemcitabine 1000 mg powder for solution for infusion

Gemcitabine

Read all of this leaflet carefully before you start receiving this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have further questions, please ask your doctor, nurse or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.

In this leaflet:

1.    What Gemcitabine powder for solution for infusion is and what it is used for

2.    Before you are given Gemcitabine powder for solution for infusion

3.    How Gemcitabine powder for solution for infusion is given

4.    Possible side effects

5.    How to store Gemcitabine powder for solution for infusion

6.    Further information

1.    WHAT GEMCITABINE POWDER FOR SOLUTION FOR INFUSION IS AND WHAT IT IS USED FOR

Gemcitabine powder for solution for infusion belongs to a group of medicines called “cytotoxics”. These medicines kill dividing cells, including cancer cells.

Gemcitabine powder for solution for infusion may be given alone or in combination with other anti-cancer medicines, depending on the type of cancer.

Gemcitabine powder for solution for infusion is used in the treatment of the following types of cancer:

•    non-small cell lung cancer (NSCLC), alone or together with cisplatin

•    pancreatic cancer.

•    breast cancer, together with paclitaxel.

•    ovarian cancer, together with carboplatin.

•    bladder cancer, together with cisplatin.

2.    BEFORE YOU ARE GIVEN GEMCITABINE POWDER FOR SOLUTION FOR INFUSION

You should not be given Gemcitabine powder for solution for infusion:

-    if you are allergic (hypersensitive) to gemcitabine or any of the other ingredients of Gemcitabine powder for solution for infusion.

-    if you are breast-feeding

Take special care with Gemcitabine powder for solution for infusion:

Before the first infusion you will have samples of your blood taken to evaluate if you have sufficient kidney and liver function. Before each infusion you will have samples of your blood taken to evaluate if you have enough blood cells to receive Gemcitabine powder for solution for infusion. Your doctor may decide to change the dose or delay treating you depending on your general condition and if your blood cell counts are too low. Periodically you will have samples of your blood taken to evaluate your kidney and liver function.

Please tell your doctor if:

•    you have, or have previously had liver disease, heart disease or vascular disease.

•    you have recently had, or are going to have radiotherapy,

•    you have been vaccinated recently

•    you develop breathing difficulties or feel very weak and are very pale (may be a sign of kidney failure).

Men are advised not to father a child during and up to 6 months following treatment with Gemcitabine powder for solution for infusion. If you would like to father a child during the treatment or in the 6 months following treatment, seek advice from your doctor or pharmacist. You may want to seek counselling on sperm storage before starting your therapy.

Taking other medicines

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other medicines, including vaccinations and medicines obtained without a prescription.

Pregnancy and breast-feeding

If you are pregnant, or thinking about becoming pregnant, tell your doctor. The use of Gemcitabine powder for solution for infusion should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Gemcitabine powder for solution for infusion during pregnancy.

If you are breast-feeding, tell your doctor.

You must discontinue breast-feeding during Gemcitabine powder for solution for infusion treatment.

Driving and using machines

Gemcitabine powder for solution for infusion may make you feel sleepy, particularly if you have consumed any alcohol. Do not drive a car or use machinery until you are sure that Gemcitabine powder for solution for infusion treatment has not made you feel sleepy.

Important information about some of the ingredients of Gemcitabine powder for solution for infusion

Gemcitabine powder for solution for infusion contains 3.9 mg (< 1 mmol) of sodium in each 200 mg vial and 19.6 mg (< 1 mmol) sodium in each 1000 mg vial. To be taken into consideration by patients on a controlled sodium diet.

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3.    HOW GEMCITABINE POWDER FOR SOLUTION FOR INFUSION IS GIVEN

The usual dose of Gemcitabine powder for solution for infusion is 1000-1250 mg for every square metre of your body’s surface area. Your height and weight are measured to work out the surface area of your body. Your doctor will use this body surface area to work out the right dose for you. This dosage may be adjusted, or treatment may be delayed depending on your blood cell counts and on your general condition.

How frequently you receive your Gemcitabine infusion depends on the type of cancer that you are being treated for.

A hospital pharmacist or doctor will have dissolved the Gemcitabine powder before it is given to you.

You will always receive Gemcitabine powder for solution for infusion by infusion into one of your veins. The infusion will last approximately 30 minutes.

If you have further questions on the use of this product ask your doctor or pharmacist.

4.    POSSIBLE SIDE EFFECTS

Like all medicines, Gemcitabine powder for solution for infusion can cause side effects, although not everybody gets them.

Frequencies of the observed side effects are defined as:

•    very common: affects more than 1 user in 10

•    common: affects 1 to 10 users in 100

•    uncommon: affects 1 to 10 users in 1,000

•    rare: affects 1 to 10 users in 10,000

_    • very rare: affects less than 1 user in 10,000

•    not known: frequency can’t be estimated from the available data

You must contact your doctor immediately if you notice any of the following:

•    Fever or infection (common): if you have a temperature of 38°C or greater, sweating or other signs of infection (since you might have less white blood cells than normal which is very common).

•    Irregular heart rate (arrhythmia) (frequency not known).

•    Pain, redness, swelling or sores in your mouth (common).

•    Allergic reactions: if you develop skin rash (very common) / itching (common), or fever (very common).

•    Tiredness, feeling faint, becoming easily breathless or if you look pale (since you might have less haemoglobin than normal which is very common).

•    Bleeding from the gums, nose or mouth or any bleeding that would not stop, reddish or pinkish urine, unexpected bruising (since you might have less platelets than normal which is very common).

•    Difficulty breathing (it is very common to have mild breathing difficulty soon after the Gemcitabine infusion which soon passes, however uncommonly or rarely there can be more severe lung problems)

Side effects with Gemcitabine powder for solution for infusion may include:

Very common side effects

Low haemoglobin level (anaemia)

Low white blood cells Low platelet count Difficulty breathing Vomiting Nausea

Skin rash- allergic skin rash, frequently itchy Hair loss

Liver problems: found through abnormal blood test results Blood in urine

Abnormal urine tests: protein in urine

Flu like symptoms including fever

Oedema (swelling of ankles, fingers, feet, face)

Common side effects

Fever accompanied by low white blood cell count (febrile neutropaenia)

Anorexia (poor appetite)

Headache

Insomnia

Sleepiness

Cough

Runny nose

Constipation

Diarrhoea

Pain, redness, swelling or sores in the mouth

Itching

Sweating

Muscle pain

Back pain

Fever

Weakness

Chills

Uncommon side effects

Interstitial pneumonitis (scarring of the air sacs of the lung)

Spasm of the airways (wheeze)

Abnormal chest X ray/scan (scarring of the lungs)

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Rare side effects

Heart attack (myocardial infarction)

Low blood pressure

Skin scaling, ulceration or blister formation Injection site reactions

Very rare side effects

Increased platelet count

Anaphylactic reaction (severe hypersensitivity/ allergic reaction)

Sloughing of skin and severe skin blistering

Side effects with frequency not known

Irregular heart beat (arrhythmia)

Adult Respiratory Distress Syndrome (severe lung inflammation causing respiratory failure) Radiation recall-(a skin rash like severe sunburn) which can occur on skin that has previously been exposed to radiotherapy.

Fluid in the lungs

Radiation toxicity- scarring of the air sacs of the lung associated with radiation therapy Ischaemic colitis (inflammation of the lining of the large bowel, caused by reduced blood supply) Heart failure Kidney failure

Gangrene of fingers or toes

Serious liver damage, including liver failure

Stroke

You might have any of these symptoms and/or conditions. You must tell your doctor as soon as possible when you start experiencing any of these side effects.

If you are concerned about any side effects, talk to your doctor.

If any of the side effects gets serious, or if you notice any side effects not mentioned in this leaflet, please tell your doctor.

5.    HOW TO STORE GEMCITABINE POWDER FOR SOLUTION FOR INFUSION

Keep out of the reach and sight of children.

Do not refrigerate or freeze.

Do not use after the expiry date (EXP) which is stated on the carton and the vial.

The expiry date refers to the last day of that month.

Reconstituted solution: The product should be used immediately. When prepared as directed, chemical and physical in-use stability of reconstituted solutions of gemcitabine were demonstrated for 24 hours at 25°C. Further dilution by a healthcare provider may be done. Solutions of reconstituted gemcitabine should not be refrigerated or frozen, as crystallisation may occur.

This medicine is for single use only; any unused solution should be discarded under the local requirements.

6.    FURTHER INFORMATION

What Gemcitabine powder for solution for infusion contains

The active substance is gemcitabine. Each vial contains 200 or 1000 mg of gemcitabine (as gemcitabine hydrochloride).

The other ingredients are mannitol (E421), sodium acetate and sodium hydroxide.

What Gemcitabine powder for solution for infusion looks like and contents of the pack

Gemcitabine powder for solution for infusion is a white to off-white powder, for solution for infusion in a vial. Each vial contains 200 or 1000 mg of gemcitabine. Each pack of Gemcitabine powder for solution for infusion contains 1 or 5 vial(s). Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

EBEWE Pharma Ges.m.b.H. Nfg. KG Mondseestrasse 11 4866 Unterach Austria

Manufacturer:

Actavis Italy S.p.A.

Nerviano Plant Viale Pasteur 10 20014 Nerviano Italy

This medicinal product is authorised in the Member States of the EEA under the following names:

BE	Gemcitabine Sandoz 200 mg/1000 mg poeder voor oplossing voor infusie
BG	Gemcitabin “Ebewe” 200 mg/1000 mg powder for solution for infusion
CY	Gemcitabin “Ebewe” 200 mg/1000 mg powder for solution for infusion
CZ	Gemcitabin Ebewe 200 mg/1000 mg prasek pro prfpravu infuznfho roztoku
DE	Gemcitabin HEXAL 200 mg/1000mg Pulver zur Herstellung einer Infusionslosung
DK	Gemcitabin Ebewe
EE	Gemcitabine Ebewe 200 mg/1000 mg
EL	Gemcitabine Ebewe 200 mg/1000 mg kovi^ yta dtd^Y^a ppoq sy%ysh
ES	Gemcitabina Ebewe 200 mg/1000 mg polvo para solucion para perfusion
FI	Gemcitabin “Ebewe” 200mg/1000mg infuusiokuiva-aine, liuosta varten
HU	Gemcitabin Ebewe 200 mg/1000 mg powder for solution for infusion
IE	Gemcitabine “Ebewe” 200 mg/1000 mg powder for solution for infusion
IT	Gemcitabina Ebewe 200 mg/1000 mg polvere per soluzione per infusione
LT	Gemcitabin Ebewe 200 mg/1000 mg powder for solution for infusion
LU	Gemcitabine Sandoz 200mg/1000mg, poudre pour solution pour perfusion
LV	Gemcitabin “Ebewe” 200 mg/1000 mg powder for solution for infusion
MT	Gemcitabin “Ebewe” 200 mg/1000 mg powder for solution for infusion
NL	Gemcitabine “Ebewe”, 200 mg/1000 mg poeder voor oplossing voor infusie
NO	Gemcitabin “Ebewe” 200mg/1000mg pulver til infusjonsvsske, opplosning
PL	Gemcitabin-Ebewe
PT	Gemcitabina Ebewe Po para solugao para perfusao
RO	Gemcitabina Ebewe 200 mg/1000 mg pulbere pentru solutie perfuzabila
SE	Gemcitabin Ebewe, 200 mg/1000 mg pulver till infusionsvatska, losning
SI	Gemcitabin “Ebewe” 200 mg/1000 mg prasek za raztopino za infundiranje
SK	Gemcitabin Ebewe 200 mg/1000 mg prasok na infuzny roztok
UK	Gemcitabine 200 mg/1000 mg powder for solution for infusion

This leaflet was last approved in 08/2010. .

The following information is intended for medical or healthcare professionals only: Instructions for use, handling and disposal.

1.    Use aseptic techniques during the reconstitution and any further dilution of gemcitabine for intravenous infusion administration.

2.    Calculate the dose and the number of Gemcitabine powder for solution for infusion vials needed.

3.    Reconstitute 200 mg vials with 5 ml of 9 mg/ml (0.9 %) sterile sodium chloride solution for injection, without preservative, or 25 ml sterile sodium chloride solution for injection, without preservative to the 1000 mg vial. Shake to dissolve. The total volume after reconstitution is 5.26 ml (200 mg vial) or 26.3 ml (1000 mg vial) respectively. This dilution yields a gemcitabine concentration of 38 mg/ml, which includes accounting for the displacement volume of the lyophilised powder. Further dilution with sterile sodium chloride 9 mg/ml (0.9%) solution for injection, without preservative may be done. The resulting solution is clear and ranges in colour from colourless to light straw-coloured.

4.    Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, do not administer.

5.    Solutions of reconstituted gemcitabine should not be refrigerated or frozen, as crystallisation may occur. Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility

of the user and would normally not be longer than 24 hours at room temperature, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

6.    Gemcitabine solutions are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

Preparation and administration precautions

The normal safety precautions for cytostatic agents must be observed when preparing and disposing of the infusion solution. Handling of the solution for infusion should be done in a safety box and protective coats and gloves should be used. If no safety box is available, the equipment should be supplemented with a mask and protective glasses.

If the preparation comes into contact with the eyes, this may cause serious irritation. The eyes should be rinsed immediately and thoroughly with water. If there is lasting irritation, a doctor should be consulted. If the solution is spilled on the skin, rinse thoroughly with water.

Disposal

Any unused product should be disposed of in accordance with local requirements.

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