PACKAGE LEAFLET: INFORMATION FOR THE USER

Gemcitabine 38 mg/ml powder for solution for infusion

Gemcitabine

Read all of this leaflet carefully before you start taking 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 or pharmacist.

-    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 or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

1.    What Gemcitabine is and what it is used for

2.    What you need to know before you use Gemcitabine

3.    How to use Gemcitabine

4.    Possible side effects

5.    How to store Gemcitabine

6.    Contents of the pack and other Information

1.    What Gemcitabine is and what it is used for

Gemcitabine belongs to a group of medicines called "cytotoxics”. These medicines kill dividing cells, including cancer cells.

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

Gemcitabine 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.    What you need to know before you use Gemcitabine Do not use Gemcitabine

•    if you are allergic (hypersensitive) to gemcitabine or any of the other ingredients of Gemcitabine

•    if you are breast-feeding

Warnings and precautions

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. 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. 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.

Other medicines and Gemcitabine

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.

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The following information is intended for medical or healthcare Instructions for use

Cytotoxic

Handling

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.

Pregnancy and breast-feeding

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

If you are breast-feeding, tell your doctor. You must discontinue breast-feeding during Gemcitabine treatment.

Driving and using machines

Gemcitabine 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 treatment has not made you feel sleepy.

Important information about some of the ingredients of Gemcitabine

Gemcitabine powder contains 3.56 mg (< 1 mmol) sodium in each 200 mg vial and 17.81 mg (< 1 mmol) sodium in each 1 g vial and 35.62 mg (1.54 mmol) sodium in each 2 g vial.

To be taken into consideration by patients on a controlled sodium diet.

3.    How to use Gemcitabine

The usual dose of Gemcitabine 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 by infusion into one of your veins. The infusion will last approximately 30 minutes.

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

4.    Possible side effects

Like all medicines, Gemcitabine can cause side effects, although not everybody gets them.

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) (uncommon).

•    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 may include:

Very common side effects: may affect more than 1 in 10 people

•    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: may affect up to 1 in 10 people

•    Fever accompanied by low white blood cell count (febrile neutropenia)

•    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: may affect up to 1 in 100 people

•    Stroke

•    Irregular heart beat (arrhythmia)

•    Heart failure

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

•    Spasm of the airways (wheeze)

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

•    Serious liver damage, including liver failure

•    Kidney failure

Rare side effects: may affect up to 1 in 1,000 people

•    Heart attack (myocardial infarction)

•    Low blood pressure

•    Gangrene of fingers or toes

•    Fluid in the lungs

•    Adult Respiratory Distress Syndrome (severe lung inflammation causing respiratory failure)

•    Skin scaling, ulceration or blister formation

•    Injection site reactions

•    Radiation toxicity - scarring of the air sacs of the lung associated with radiation therapy

•    Radiation recall - (a skin rash like severe sunburn) which can occur on skin that has previously been exposed to radiotherapy.

Very rare side effects: may affect up to 1 in 10,000 people

•    Increased platelet count

•    Anaphylactic reaction (severe hypersensitivity / allergic reaction)

•    Ischaemic colitis (inflammation of the lining of the large bowel, caused by reduced blood supply)

•    Sloughing of skin and severe skin blistering.

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 you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting

side effects you can help provide more information on the safety of this medicine.

United Kingdom

Yellow Card Scheme

Tel: Freephone 0808 100 3352

Website: www.mhra.gov.uk/yellowcard

5.    How to store Gemcitabine

Keep out of the sight and reach of children.

Unopened container Do not refrigerate or freeze.

Opened container

After opening, the contents should be reconstituted, and if appropriate further diluted, and used immediately. Reconstituted solutions should not be refrigerated, as crystallisation may occur.

Do not use Gemcitabine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

Gemcitabine should not been used if there are any signs of particles.

Do not throw away 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 information What Gemcitabine contains

•    The active substance is gemcitabine (as hydrochloride).

After reconstitution one ml of Gemcitabine contains 38 mg gemcitabine. One vial Gemcitabine contains 200 mg, 1 g or 2 g gemcitabine.

•    The other ingredients are mannitol E421, sodium acetate trihydrate and sodium hydroxide 1 N (for pH adjustment)

What Gemcitabine looks like and contents of the pack

Gemcitabine powder for solution for infusion is a white to off-white compact aggregate powder. After reconstitution in 0.9% sodium chloride solution, the solution is clear to pale opalescent and colourless to pale yellow.

Gemcitabine is in colourless glass vials with bromobutylic rubber stopper. Each vial will be packed with or without a protective plastic overwrap.

Pack sizes

One vial containing 200 mg gemcitabine.

One vial containing 1 g gemcitabine.

One vial containing 2 g gemcitabine.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Aptil Pharma Limited

9th Floor, CP House, 97-107 Uxbridge Road,

Ealing, London, W5 5TL

Manufacturer

S.C. Sindan-Pharma S.R.L.

11 Ion Mihalache Blvd.

Bucharest 011171,

Romania

Actavis Nordic A/S 0rnegardsvej 16 2820 Gentofte Denmark

Actavis Italy S.p.A. - Nerviano Plant Viale Pasteur 10 20014 Nerviano (MI)

Italy

This leaflet was last revised in May 2013.    LGEM38Y-01

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Instructions for reconstitution (and further dilution, if performed)

The only approved diluent for reconstitution of gemcitabine sterile powder is sodium chloride 9 mg/ml (0.9%) solution for injection (without preservative). Due to solubility considerations, the maximum concentration for gemcitabine upon reconstitution is 40 mg/ml. Reconstitution at concentrations greater than 40 mg/ml may result in incomplete dissolution and should be avoided.

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

2.    To reconstitute, add the appropriate volume of sterile sodium chloride 9 mg/ml (0.9%) solution for injection without preservative (as stated in the table below) and shake to dissolve:

Further dilution with sterile sodium chloride 9 mg/ml (0.9 %) solution for injection, without preservative can be done. Reconstituted solution is a clear colourless to light straw-coloured solution.

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

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