PATIENT INFORMATION LEAFLET

Gemcitabine 200 mg powder for solution for infusion

Gemcitabine

In this leaflet:

1.    What Gemcitabine is and what it is used for

2.    Before you are given Gemcitabine

3.    How Gemcitabine is given

4.    Possible side effects

5.    How to store Gemcitabine

6.    Further information

1. WHAT Gemcitabine IS AND WHAT IT IS USED FOR

Gemcitabine belongs to a group of medicines called “cyto-toxics”. 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. BEFORE YOU ARE GIVEN Gemcitabine

You should not be given Gemcitabine:

If you are allergic (hypersensitive) to gemcitabine or any of the other ingredients of Gemcitabine.

If you are breast-feeding.

Take special care with Gemcitabine

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

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The following information is intended for medical or healthcare professionals only:

Instructions for use, handling and disposal

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

2.    Calculate the dose and the number of vials of Gemcitabine 200 mg powder for solution for infusion.

blood taken to evaluate if you have enough blood cells to be able 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 a 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 week 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 counseling on sperm storage before starting your treatment.

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

Ask your doctor or pharmacist for advice before taking any medicine.

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 contains 3.5 mg (< 1 mmol) sodium in each vial. To be taken into consideration by patients on a controlled sodium diet.

3. HOW GEMCITABINE IS GIVEN

The usual dose of Gemcitabine is 1,000 - 1,250 mg for every squared meter of your body's surface area. Your weight and height 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

3.    Reconstitute each 200 mg vial with 5 ml solution for injection in sterile sodium chloride, 9 mg / ml (0.9%) without preservatives. Shake to dissolve. The total volume after reconstitution is 5.26 ml. The resulting concentration of gemcitabine is 38 mg / ml, which includes considering the volume of the lyophi-lized powder. Again it can be diluted with a solution of sodium chloride injection, 9 mg / ml (0.9%), with no preservatives. The reconstituted solution is clear colorless or pale yellow.

4. Before the administration should be inspected visually to detect the drug particles in suspension and / or discolor-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 Ge-mcitabine 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 any further questions on the use of this product, ask y our doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Gemcitabine can cause side effects,

although not everybody gets them.

Frequencies of the observed side effects are defined as:

•    very common: These may affect more than 1 in 10 people

•    common: These may affect up to 1in 10 people

•    uncommon: These may affect up to 1 in 100 people

•    rare: These may affect up to 1 in 1,000 people

•    very rare: These may affect up to 1 in 10,000 people

•    not known: frequency cannot 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 may include:

Very common side effects

-    Low hemoglobin level (anemia)

-    Low white blood cells

-    Low platelet count

-    Difficulty breathing

-    Vomiting

-    Nausea

-    Skin rash - allergic skin rash, frequently itchy

-    Hair Loss ation. If we observe the presence of particles, should not be given.

5.Solutions of reconstituted gemcitabine should not be refrigerated because crystallization can occur. It has been shown chemical and physical stability in use for 24 hours at 25 ° C. Visa from a microbiological point of the product should be used immediately. If not used immediately, conditions and storage periods before use, shall be the responsibility of the user and must not exceed 24 hours at room temperature, unless reconsti-

-    Liver problems: found through abnormal blood tests results

-    Blood in urine

-    Abnormal urine tests: proteins 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 neutropenia)

-    Anorexia (poor appetite)

-    Headache

-    Insomnia

-    Sleepiness

-    Cough

-    Runny nose

-    Constipation

-    Diarrhea

-    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)

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 been previously 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.

-    Cerebral infarction (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 or pharmacist.

5. HOW TO STORE GEMCITABINE

Keep out of the reach and sight of children.

Do not use Gemcitabine after the expiry date (EXP) which is stated on the package.

Unopened vial: store below 30 ° C. Do not refrigerate.

Do not use Gemcitabine after the expiry date which is stated on the vial or outer packaging after “EXP”.

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.You can perform a subsequent dilution by a health professional. Solutions of reconstituted gemcitabine should not be refrigerated because crystallization can occur.

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

6. ADDITIONAL INFORMATION What Gemcitabine contains

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

The other ingredients are mannitol (E421), sodium acetate trihydrate, hydrochloric acid and sodium hydroxide (as pH regulator).

What Gemcitabine looks like and contents of the pack

Gemcitabine is a white or off white powder, for solution for infusion in a vial packaging. Each vial contains 200 mg of gemcitabine. Each pack of Gemcitabine contains 1 vial.

Marketing authorization holder and Manufacturer

GP-Pharm, S.A.

Poligono Industrial Els Vinyets-Els Fogars, sector 2 Carretera Comarcal C-244, km. 22 08777 Sant Quinti de Mediona (Barcelona)

SPAIN

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

Spain: Gemcitabina GP-Pharm 200 mg polvo para solucion para perfusion EFG

Italy: Gemcitabina GP-Pharm 200 mg polvere per soluzione per infusione

Portugal: Gemcitabina GP-Pharm 200 mg po para solugao para perfusao

Greece: Gemcitabine Thama 200 mg Kovig yia SiaAupa npog

EYXuon

United Kingdom: Gemcitabine GP-Pharm 200 mg powder for solution for infusion

Germany: Gemcitabine GP-Pharm 200 mg Pulver zur Herste-llung einer Infusionslosung

Bulgaria: Gemcitabine CSC 200 mg npax 3a HH$y3HOHeH pa3TBop

Poland: Gemcitabine CSC 200 mg proszek do sporz^dzania roztworu do infuzji

Lithuania: Gemcitabine CSC 200 mg milteliai infuziniam tirpalui Latvia: Gemcitabine CSC 200 mg pulveris infuziju sklduma pagatavosanai

Estonia: Gemcitabine CSC 200 mg pulber infusioonilahuse val-mistamiseks

Czeck Republic: Gemcitabine CSC Pharmaceuticals 200 mg prasek pro pripravuinfuzniho roztoku Romania: Gemcitabina CSC 200 mg pulbere pentru soluje perfuzabila

Slovakia: Gemcitabine CSC 200 mg prasok na infuzny roztok This leaflet was last approved In October 2011.

PR-GEMCI601-GB-01

tution / dilution is carried out under aseptic conditions controlled and validated.

6.Solutions of Gemcitabine should be used only once. You must remove any unused product or waste in accordance with local rules.

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.