Gemcitabine 1g Powder For Solution For Infusion

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PREPARATION GUIDE FOR USE WITH GEMCITABINE 200 mg, 1 g AND 2 g POWDER FOR SOLUTION FOR INFUSION

Please note this is a Prescriber Information Leaflet NOT the SPC. For full details regarding this product please refer to the SPC.

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 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 1 g vial or 50 ml sterile sodium chloride solution for injection, without preservative to the 2 g vial. Shake to dissolve. The total volume after reconstitution is 5.26 ml (200 mg vial), 26.3 ml (1 g vial) or 52.6 ml (2 g 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, as crystallisation may occur. Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C for the reconstituted product with a concentration of 38 mg/ml. Chemical and physical in-use stability has been demonstrated for ambient conditions (15-25°C, ambient light) or in a refrigerator (2-8°C) for at most 72 hours (3 days) for the diluted solution at concentrations between

0.1 mg/mL and 30 mg/mL in 0.9% sodium chloride for injection. From a microbiological point of view, the reconstituted and diluted 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 (and further dilution, if applicable) 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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PACKAGE LEAFLET: INFORMATION FOR THE USER

GEMCITABINE 200 mg, 1 g AND 2 g POWDER FOR SOLUTION FOR INFUSION

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

WHAT GEMCITABINE POWDER FOR SOLUTION FOR INFUSION 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.

BEFORE YOU ARE GIVEN ^W GEMCITABINE POWDER FOR SOLUTION FOR INFUSION

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 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.

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 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.

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

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) of sodium in each 200 mg vial, 17.5 mg (< 1 mmol) sodium in each 1 g vial and 35 mg (1.5 mmol) sodium in each 2 g vial. To be taken into consideration by patients on a controlled sodium diet.

©HOW GEMCITABINE POWDER FOR SOLUTION FOR INFUSION IS GIVEN

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 product ask your doctor or hospital pharmacist.

Q 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: 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 not 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

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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 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 neutropenia)

• Anorexia (poor appetite)

• Headache

• Insomnia

• Sleepiness

• Cough

• Runny nose

• Constipation

• Diarrhoea

• Pain, redness, swelling or sores in the mouth

• Itching

• Sweating

• Muscle pain

• Fever

• Weakness

• Chills

• Back pain.

Uncommon side effects:

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

• Spasm of the airways (wheezing)

• 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 the 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.

POWDER FOR SOLUTION FOR INFUSION

Keep out of the reach and sight of children.

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

Unopened vial:

No special storage conditions are required.

Reconstituted solution:

The product should be used immediately. When prepared as directed, chemical and physical in-use stability of gemcitabine has been demonstrated for 24 hours at 25°C for the reconstituted product with a concentration of 38 mg/ml. Further dilution by a healthcare provider may be done. Solutions of reconstituted gemcitabine should not be refrigerated, as crystallisation may occur.

From a microbiological point of view, the reconstituted and diluted 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 (and further dilution, if applicable) has taken place in controlled and validated aseptic conditions.

For single use only. Discard any unused solution.

Do not use Gemcitabine if you notice any particles or visible signs of deterioration.

Medicines should not be disposed of via wastewater or household waste. Your doctor should dispose of medicines that are no longer required. These measures will help to protect the environment

Q FURTHER INFORMATION

What Gemcitabine Powder For Solution For Infusion contains

The active substance is gemcitabine. Each vial contains 200 mg, 1 g or 2 g of gemcitabine (as gemcitabine hydrochloride).

The other ingredients are mannitol (E421), sodium acetate (E262), hydrochloric acid and sodium hydroxide.

What Gemcitabine Powder For Solution For Infusion looks like and contents of the pack

Each vial of Gemcitabine contains a white to off-white powder supplied in a glass vial closed with a rubber stopper and aluminium cap with a plastic cover.

Gemcitabine 200 mg Powder for solution for infusion are available in packs containing 1,5 and 10 vials.

Gemcitabine 1 g Powder for solution for infusion are available in packs containing 1, 5 and 10 vials. Gemcitabine 2 g Powder for solution for infusion are available in packs containing 1, 5 and 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation Holder is TEVA UK Limited, Eastbourne, BN22 9AG.

Manufacturer is: Pharmachemie B.V,

2031 GA Haarlem, The Netherlands.

This leaflet was last revised in January 2010.

PL 00289/1299-1301 01036-A

01036-A

93.130.XXX.X