Package leaflet: Information for the user

)6 mn

14 mm <-

20 mm

^ -1 mm

ITF 6 mm

+1 mm

14 mm

20 mm

6 mm

if you are breast-feeding.

Warnings and precautions

Before the first infusion you will have samples of your blood taken to check if your liver and kidneys are working well enough for you to receive this medicine. Before each infusion you will have samples of your blood taken to check 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 check how well your kidneys and liver are working.

Talk to your doctor, nurse or hospital pharmacist before using Gemcitabine.

If you have, or have previously had liver disease, heart disease, vascular disease or problems with your kidneys talk to your doctor or hospital pharmacist as you may not be able to receive Gemcitabine.

If you have recently had or are going to have radiotherapy, please tell your doctor as there may be an early or late radiation reaction with Gemcitabine.

If you have been vaccinated recently, please tell your doctor as this can possibly cause bad effects with Gemcitabine.

If during treatment with this medicine you get symptoms such as headache with confusion, seizures (fits) or changes in vision, call your doctor right away. This could be a very rare nervous system side effect named posterior reversible encephalopathy syndrome.

If you develop breathing difficulties or feel very weak and are very pale, please tell your doctor as this may be a sign of kidney failure or problems with your lungs.

Continued on top of next column AAAI6631

Sfc____________________________________________________

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 diluted the Gemcitabine concentrate 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.

This medicinal product is not recommended for use in children under 18 years of age.

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

4| Possible side effects

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

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

•    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).

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

Continued over page

The following information is intended for healthcare professionals only: Instruction for use

Gemcitabine 40mg/ml Concentrate for Solution for Infusion

Cytotoxic

Handling

The normal safety precautions for cytostatic agents must be observed when preparing and disposing of the infusion solution. Pregnant personnel should not handle the product. 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 mmediately 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.

Continued on top of next column_

^ 5 mm

Instructions for dilution

The only approved diluent for dilution of Gemcitabine Concentrate for Solution for Infusion is sodium chloride 9mg/ml (0.9%) solution for injection (without preservative).

•    Use aseptic technique during dilution of gemcitabine for intravenous infusion administration.

•    Diluted solution is a clear colourless or light straw-coloured solution.

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

Continued over page

__N. 000000000.0

1

2

3

4

5

6

7

8    9    10    11

10 mm

I I I I I I I I I I I

10 mm

Allergic reactions: Mild to moderate skin rash (very common); itching (common); or fever (very common). Temperature of 38°C or greater, sweating or other signs of infection (since you might have less white blood cells than normal accompanied by fever also known as febrile neutropenia) (common).

Pain, redness, swelling or sores in your mouth (stomatitis) (common). Irregular heart rate (arrhythmia) (uncommon).

Extreme tiredness and weakness, purpura or small areas of bleeding in the skin (bruises), acute renal failure (low urine output /or no urine output), and signs of infection (haemolytic uraemic syndrome).

It may be fatal (uncommon).

Difficulty breathing (it is 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).

Severe chest pain (myocardial infarction) (rare).

Severe hypersensitivity/allergic reaction with severe skin rash including red itchy skin, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), wheezing, fast beating heart and you may feel you are going to faint (anaphylactic reaction) (very rare).

Generalised swelling, shortness of breath or weight gain, as you might have fluid leakage from small blood vessels into the tissues (capillary leak syndrome) (very rare).

Headache with changes in vision, confusion, seizures or fits (posterior reversible encephalopathy syndrome) (very rare).

Severe rash with itching, blistering or peeling of the skin, often accompanied by flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).

Other side effects with Gemcitabine may include:

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

Low white blood cells

Difficulty breathing

Vomiting

Nausea

Hair loss

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

Abnormal urine tests: protein in urine Flu like symptoms including fever Swelling of ankles, fingers, feet, face (oedema)

Low Haemoglobin level (anaemia).

Common side effects (may affect up to 1 in 10 people)

Poor appetite (anorexia)

Headache

Insomnia

Sleepiness

Cough

Runny nose

Constipation

Diarrhoea

Itching

Sweating

Muscle pain

Back pain

Fever

Weakness

Chills.

Uncommon side effects (may affect up to 1 in 100 people)

Scarring of the air sacs of the lung (interstitial pneumonitis)

Wheeze (spasm of the airways)

Scarring of the lungs (abnormal chest X ray/scan)

Heart failure Kidney failure

Serious liver damage, including liver failure which could be life- threatening Stroke.

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

Low blood pressure

Skin scaling, ulceration or blister

formation

Sloughing of the skin and severe skin blistering

Injection site reactions Severe lung inflammation causing respiratory failure (adult respiratory distress syndrome)

A skin rash like severe sunburn which can occur on skin that has previously been exposed to radiotherapy (radiation recall)

Fluid in the lungs Scarring of the air sacs of the lung associated with radiation therapy (radiation toxicity)

Gangrene of fingers or toes Inflammation of the blood vessels (peripheral vasculitis).

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

Increased platelet count Inflammation of the lining of the large bowel, caused by reduced blood supply (ischemic colitis).

Low haemoglobin level (anaemia), low white blood cells and low platelet count will be detected by a blood test.

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.

Continued on top of next column AAAI6631

•rfr.____________________________________________________

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse.

This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard

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

How to store Gemcitabine

Keep this medicine out of the sight and reach of children.

Unopened container

Store in a refrigerator (2°C - 8°C).

After first opening

Chemical and physical in use stability has been demonstrated for 28 days at 25°C.

From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Solution for infusion

Chemical and physical in-use stability has been demonstrated for 28 days at 2°C to 8°C and about 25°C upon dilution in 0.9% sodium chloride solution to a final concentration in the range between 2 - 25mg/ml (2.0mg/ml, 12mg/ml and 25mg/ml). Diluted solutions are stable when packaged into either PVC or PE infusion bags.

From a microbiological point of view, the solution for infusion 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 2°C to 8°C unless dilution has taken place in controlled and validated aseptic conditions.

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

Do not use this medicine if you notice any signs of particles.

6| Contents of the pack and other information

What Gemcitabine contains

•    The active substance is gemcitabine (as gemcitabine hydrochloride).

Each ml of concentrate for solution for infusion contains 40mg gemcitabine (as gemcitabine hydrochloride). Each 5ml vial contains 200mg gemcitabine (as gemcitabine hydrochloride). Each 25ml vial contains 1g gemcitabine (as gemcitabine hydrochloride).

Each 50ml vial contains 2g gemcitabine (as gemcitabine hydrochloride).

•    The other ingredients are hydrochloric acid (E-507) for pH adjustment, water for injections.

What Gemcitabine looks like and contents of the pack

Gemcitabine Concentrate for Solution for Infusion is a clear, colourless or pale yellow solution.

Gemcitabine is contained in type I colourless glass vials with bromobutyl rubber stoppers and sealed with aluminium caps with polypropylene disc. Each vial will be packed with or without a protective plastic overwrap.

Pack sizes

1 x 5ml vial 1 x 25ml vial 1 x 50ml vial

Marketing Authorisation Holder

Actavis Group PTC ehf. Reykjavikurvegi 76-78 220 HafnarfjorSur Iceland

Manufacturer

Actavis Italy S.p.A.

Nerviano Plant Viale Pasteur 10 20014 Nerviano (MI)

Italy

This leaflet was last revised in January 2016

If you would like a leaflet with larger text, please contact 01271 385257.

Actavis

Actavis, Barnstaple, EX32 8NS, UK

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

Storage conditions After first opening

Chemical and physical in use stability has been demonstrated for 28 days at 25°C.

From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately. If not used mmediately, in-use storage times and conditions are the responsibility of the user.

Solution for infusion

Chemical and physical in-use stability has been demonstrated for 28 days at 2°C to 8°C and about 25°C upon dilution in 0.9% sodium chloride solution to a final concentration in the range between 2 - 25mg/ml (2.0mg/ml, 12mg/ml and 25mg/ml).

Continued on top of next column AAAI6631

The pH of the diluted solution is in the range of 2-3 and the osmolality is approximately 285 mOsm/kg. Diluted solutions are stable when packaged into either PVC or PE infusion bags. From a microbiological point of view, the solution for infusion 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 2°C to 8°C unless dilution has taken place in controlled and validated aseptic conditions.

Actavis

Actavis, Barnstaple, EX32 8NS, UK