GEMCITABINE FLYNN 200 mg POWDER FOR SOLUTION FOR INFUSION

2. Before you use Gemcitabine Flynn powder for solution for infusion

Do not use Gemcitabine FLYNN powder for solution for infusion

• If you are allergic (hypersensitive) to gemcitabine or any of the other ingredients of Gemcitabine FLYNN powder for solution for infusion.
• If you are breast-feeding, you must stop breast-feeding before starting treatment with Gemcitabine.

Take special care with Gemcitabine FLYNN powder for solution for infusion

Before the first infusion, blood samples will be taken to check if your liver and kidney function is normal. Also, before each infusion, blood samples will be taken to check if you have enough red blood cells to receive Gemcitabine. Your doctor may decide to change the dose or delay treatment depending on your general health and your blood cell counts. Periodically, blood samples will be taken to check your kidney and liver function.

Tell your doctor if:

• You have or have had liver, heart or vascular disease.
• You have recently received or are going to receive radiotherapy.
• You have recently been vaccinated.
• You have difficulty breathing or feel very weak and very pale (this could be a sign of kidney failure).

Men are advised not to father a child during treatment with Gemcitabine and for 6 months after treatment. If you wish to father a child during treatment or in the 6 months after treatment, consult your doctor or pharmacist. You may want to seek advice on sperm conservation before starting treatment.

Using other medicines

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

Pregnancy and breast-feeding

If you are pregnant or think you may be pregnant, tell your doctor. Gemcitabine should be avoided during pregnancy. Your doctor will discuss with you the potential risks of taking Gemcitabine during pregnancy.

Tell your doctor if you are breast-feeding.

You must stop breast-feeding during treatment with Gemcitabine.

Driving and using machines

Gemcitabine may cause drowsiness, especially if you have consumed alcohol. Avoid driving or using machines until you are sure that treatment with Gemcitabine does not make you drowsy.

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

Gemcitabine FLYNN powder for solution for infusion contains 3.5 mg (less than 1 mmol) of sodium per 200 mg vial. Patients on a controlled sodium diet should be aware of this.

3. How to use Gemcitabine Flynn powder for solution for infusion

The usual dose of Gemcitabine is 1,000-1,250 mg per square meter of your body surface area. Your height and weight will be measured to calculate the area of your body. Your doctor will use this body surface area to calculate the correct dose for you. This dose may be adjusted or treatment delayed depending on your general health and your blood cell counts.

The frequency of your Gemcitabine infusion depends on the type of cancer being treated.

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

You will always receive Gemcitabine by infusion into one of your veins. The infusion will take about 30 minutes.

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

4. Possible side effects

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

The frequencies of side effects are defined as:

• Very common, affects more than 1 in 10 patients treated
• Common, affects between 1 and 10 in 100 patients treated
• Uncommon, affects between 1 and 10 in 1,000 patients treated
• Rare, affects between 1 and 10 in 10,000 patients treated
• Very rare, affects less than 1 in 10,000 patients treated
• Not known, frequency cannot be estimated from the available data

You should contact your doctor immediately if you experience any of the following

effects:

• Fever or infection (common): if you have a temperature of 38°C or higher, sweating or other signs of infection (as you may have a lower than normal white blood cell count, which is very common).
• Irregular heartbeat (frequency not known).
• Pain, redness, swelling or ulcers in the mouth (common).
• Allergic reactions: if you experience a rash (very common) / itching (common), or fever (very common).
• Tiredness, feeling faint, getting breathless easily or if you are pale (as you may have a lower than normal red blood cell count, which is very common).
• Bleeding from the gums, nose or mouth or any bleeding that does not stop, red or pink urine, unexpected bruising (as you may have a lower than normal platelet count, which is very common).
• Difficulty breathing (it is very common to have mild breathing difficulties immediately after Gemcitabine infusion, which soon pass; however, less commonly or rarely, more serious lung problems can occur)

The following side effects may occur with Gemcitabine:

Very common side effects

• Low red blood cell count (anaemia)
• Low white blood cell count
• Low platelet count
• Breathing difficulties
• Vomiting
• Feeling sick
• Rash - allergic skin rash, often with itching
• Hair loss
• Liver problems: identified through abnormal blood test results
• Blood in the urine
• Abnormal urine tests: protein in the urine
• Pseudo-flu syndrome including fever
• Swelling (swelling of the ankles, fingers, feet, face)

Common side effects

• Fever with a low white blood cell count
• Lack of appetite
• Headache
• Insomnia
• Drowsiness
• Cough
• Stuffy nose
• Constipation
• Diarrhoea
• Pain, redness, swelling or ulcers in the mouth
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills

Uncommon side effects

• Interstitial pneumonitis (scarring of the lungs)
• Spasm of the airways (wheezing)
• Abnormal chest X-ray/scan (scarring of the lungs)

Rare side effects

• Heart attack (myocardial infarction)
• Low blood pressure
• Peeling of the skin, ulcers or blistering
• Reactions at the injection site

Very rare side effects

• High platelet count
• Anaphylactic reactions (severe hypersensitivity/allergic reaction)
• Severe peeling of the skin and blistering

Side effects of unknown frequency

• Irregular heartbeat (arrhythmia)
• Adult respiratory distress syndrome (severe lung inflammation causing respiratory failure)
• Delayed radiation toxicity - skin rash similar to severe sunburn (which can occur in skin that has been previously exposed to radiotherapy)
• Fluid in the lungs
• Radiation toxicity - scarring of the lungs associated with radiotherapy
• Ischaemic colitis (inflammation of the lining of the large intestine, caused by reduced blood supply)
• Heart failure
• Kidney failure
• Gangrene of the fingers or toes
• Severe liver damage, including liver failure
• Stroke (cerebral infarction)

You may experience any of these symptoms and/or conditions. You should inform your doctor as soon as possible if you start to experience side effects.

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

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. Storage of Gemcitabine Flynn powder for solution for infusion

Keep out of the reach and sight of children.

Do not use Gemcitabine FLYNN powder for solution for infusion after the expiry date (EXP) stated on the carton.

Sealed vial: store at a temperature below 25°C

Reconstituted solution: the product should be used immediately. When prepared according to the instructions, the chemical and physical properties of the reconstituted gemcitabine solutions have been shown to be stable for 24 hours at 20-25°C. Further dilution may be performed by a healthcare professional. Reconstituted gemcitabine solutions should not be refrigerated as crystallization may occur.

This medicinal product should be used only once. Disposal of unused medicinal product or waste material should be in accordance with local requirements.

6. Further information

What Gemcitabine FLYNN powder for solution for infusion contains

• The active substance is gemcitabine. Each vial contains 200 mg of gemcitabine (as gemcitabine hydrochloride).
• The other ingredients are mannitol (E421), sodium acetate, hydrochloric acid and sodium hydroxide.

Appearance of Gemcitabine FLYNN powder for solution for infusion and pack contents

Gemcitabine FLYNN is a white or almost white powder or compacted powder for solution for infusion in a vial. Each vial contains 200 mg of gemcitabine. Each pack of Gemcitabine FLYNN powder for solution for infusion contains 1 vial.

Marketing authorisation holder:

Flynn Pharma Ltd

Alton House, 4 Herbert Street, Dublin 2

Ireland

Manufacturer

THYMOORGAN PHARMAZIE GMBH

Schiffgraben, 23 (Vienenburg)

Germany

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

This leaflet was approved in April 2010

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INFORMATION FOR HEALTHCARE PROFESSIONALS

Gemcitabine FLYNN 200 mg powder for solution for infusion

The following information is intended for healthcare professionals only:

Instructions for use, handling and disposal

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

1. Calculate the dose and the number of vials of Gemcitabine required.

1. Reconstitute each 200 mg vial with 5 ml of sterile sodium chloride injection solution, 9 mg/ml (0.9%) without preservatives, or each 1,000 mg vial with 25 ml of sterile sodium chloride injection solution, 9 mg/ml (0.9%) without preservatives. Shake to dissolve. The total volume after reconstitution is 5.26 ml (200 mg vial) or 26.3 ml (1,000 mg vial) respectively. The resulting concentration of gemcitabine is 38 mg/ml, taking into account the displacement volume of the lyophilized powder. Further dilution may be performed with a sodium chloride injection solution, 9 mg/ml (0.9%), without preservatives. The reconstituted solution is a clear, colourless or pale yellow solution.

1. Before administration, the medicinal product should be inspected visually for particulate matter and/or discolouration. If particulate matter is observed, the medicinal product should not be administered.

1. The reconstituted gemcitabine solutions should not be refrigerated as crystallization may occur. Chemical and physical stability has been demonstrated for 24 hours at 20-25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and should not exceed 24 hours at room temperature.

1. Gemcitabine solutions should be used only once. Any unused product or waste material should be disposed of in accordance with local requirements.

Precautions for preparation and administration

Normal safety precautions for cytostatic agents should be taken when preparing and disposing of the infusion solution. Handling of the solution should be performed in a safety cabinet and protective clothes and gloves should be worn. If a safety cabinet is not available, protective clothing and gloves should be supplemented with a mask and eye protection.

If the preparation comes into contact with the eyes, it may cause serious irritation. The eyes should be rinsed immediately and thoroughly with plenty of water. If irritation persists, a doctor should be consulted. If the solution is spilled on the skin, the area should be rinsed thoroughly with plenty of water.

Disposal

Disposal of unused medicinal product or waste material should be in accordance with local requirements.