GEMCITABINE MEDAC 38 MG / ML POWDER FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

Gemcitabine

38 mg/ml powder for solution for infusion Gemcitabine

Read all of this leaflet carefully before you start receiving 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 nurse.
• 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 nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Gemcitabine is and what it is used for

• 2. What you need to know before you are given Gemcitabine

• 3. How Gemcitabine is given

• 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 adults for the treatment of the following types of cancer:

• bladder cancer, together with cisplatin
• pancreatic cancer
• non-small cell lung cancer (NSCLC), alone or together with cisplatin
• ovarian cancer, together with carboplatin
• breast cancer, together with paclitaxel.

2. what you need to know before you are given gemcitabine

You should not be given Gemcitabine:

• if you are allergic to gemcitabine or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding.

Warnings and precautions

Talk to your doctor or nurse before you are given 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.
• have recently had, or are going to have radiotherapy.
• have been vaccinated recently.
• get symptoms during treatment with this medicine, such as headache with confusion, seizures (fits) or changes in vision. This could be a very rare nervous system side effect named posterior reversible encephalopathy syndrome.
• develop breathing difficulties or feel very weak and are very pale. These may be signs of kidney failure or problems with your lungs.
• develop generalised swelling, shortness of breath or weight gain. These may be signs of fluid leaking from your small blood vessels into the tissue.

Children and adolescents

This medicine is not recommended for use in children under 18 years of age due to insufficient data on safety and efficacy.

Other medicines and Gemcitabine

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding and fertility

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

The use of Gemcitabine should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Gemcitabine during pregnancy.

Breast-feeding

If you are breast-feeding, tell your doctor.

You must not breast-feed during treatment with Gemcitabine.

Fertility

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.

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.

Gemcitabine contains sodium

200 mg and 1,000 mg vial

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

1,500 mg vial

This medicine contains 26.3 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.3 % of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Gemcitabine is given

The recommended dose of Gemcitabine is

1,000 – 1,250 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 dose 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 any further questions on the use of this medicine, 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:

• Temperature of 38°C or higher, 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).
• 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, also known as thrombocytopenia) (very common).
• Difficulty breathing (dyspnoea), it is very common to have mild breathing difficulty soon after the Gemcitabine infusion which soon passes, however uncommonly or rarely this may be a sign of more severe lung problems (pulmonary oedema/interstitial pneumonitis/adult respiratory distress syndrome).
• Shortness of breath, excessive tiredness, leg swelling (might be symptoms for heart failure) (uncommon).

The following information is intended for healthcare professionals only:

Special precautions for disposal and other handling

Reconstitution:

For single use only.

This medicinal product has only been shown to be compatible with sodium chloride 9 mg/ml (0.9 %) solution for injection. Accordingly, only this diluent should be used for reconstitution. Compatibility with other active substances has not been studied. Therefore, it is not recommended to mix this medicinal product with other active substances when reconstituted.

Reconstitution at concentrations greater than 38 mg/ ml may result in incomplete dissolution, and should be avoided.

To reconstitute, slowly add the appropriate volume of sodium chloride 9 mg/ml (0.9 %) solution for injection (as stated in the table below) and shake to dissolve.

Presentation	Presentation volume of sodium chloride 9 mg/ml (0.9 %) solution for injection to be added	Reconstituted volume	Final concentration
200 mg	5 ml	5.26 ml	38 mg/ml
1,000 mg	25 ml	26.3 ml	38 mg/ml
1,500 mg	37.5 ml	39.5 ml	38 mg/ml

The appropriate amount of this medicinal product may be further diluted with sodium chloride 9 mg/ml (0.9 %) solution for injection.

Parenteral medicinal products should be inspected visually for particulate matter and discolouration, prior to administration, whenever solution and container permit. Any unused solution should be discarded as described below.

Guidelines for the safe handling of cytotoxic medicinal products:

Local guidelines on safe preparation and handling of cytotoxic medicinal products must be adhered to. Cytotoxic preparations should not be handled by pregnant staff. The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicines used. This should be performed in a designated area. The work surface should be covered with disposable plastic-backed absorbent paper.

Suitable eye protection, disposable gloves, face mask and disposable apron should be worn. Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. If accidental contamination occurs, the eyes should be washed with water thoroughly and immediately.

Syringes and infusion sets should be assembled carefully to avoid leakage (use of Luer lock fittings is recommended). Large bore needles are recommended to minimise pressure and the possible formation of aerosols. The latter may also be reduced by the use of a venting needle.

Actual spillage or leakage should be mopped up wearing protective gloves. Excreta and vomit must be handled with care.

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

। These may be features of thrombotic microangiopathy (clots forming in small blood vessels) and haemolytic uraemic syndrome, which may be fatal (very rare).

• Paralysis of face and extremities (mostly one-sided), visual disturbances, speech disorders, numbness (might be symptoms of stroke) (uncommon).
• Yellowing of skin/whites of eyes, nausea, fatigue, diarrhoea, mental disorientation (might be symptoms for serious liver damage, including liver failure) (uncommon).
• Severe chest pain, heart attack (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 (anaphylactoid 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 (might be symptoms for posterior reversible encephalopathy syndrome) (very rare).

Side effects with Gemcitabine may include:

Very common: may affect more than 1 in 10 people

• Tiredness, feeling faint, becoming easily breathless or if you look pale (may be symptoms for anaemia)
• Low white blood cells (leukopenia)
• V Vomiting
• Nausea
• Allergic skin rash, frequently itchy
• Hair loss (alopecia)
• Liver problems: found through abnormal blood test results
• Blood in urine (haematuria)
• Abnormal urine tests: protein in urine (proteinuria)
• Flu-like symptoms including fever, the most common symptoms are fever, headache, chills, muscle pain, weakness and poor appetite. Cough, runny nose, discomfort, sweating and sleeping difficulties have also been reported.
• Swelling of ankles, fingers, feet, face (oedema)

Common: may affect up to 1 in 10 people

• Poor appetite (anorexia)
• Headache
• Insomnia
• Sleepiness
• Cough
• Runny nose (rhinitis)
• Constipation
• Diarrhoea
• Pain, redness, swelling or sores in the mouth (stomatitis)
• Itching
• Sweating
• Muscle pain (myalgia)
• Back pain
• Fever
• Weakness (asthenia)
• Chills
• Infections

Uncommon: may affect up to 1 in 100 people

• Wheeze (bronchospasm)
• Abnormal chest X ray/scan (scarring of the lungs)
• Irregular heart beat (arrhythmia)
• Weakness, shortness of breath, confusion, lethargy (may be symptoms for kidney failure)

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

• Low blood pressure (hypotension)
• Severe skin reactions, including scaling and blister formation
• Ulceration of the skin
• Vesicle and sore formation on the skin
• Scaling of the skin
• Injection site reactions – mainly mild in nature
• Problems with blood flow to the limbs. If it is severe and lasts a long time, the hands or feet may become dead and black (gangrene)
• Inflammation of blood vessels (peripheral vasculitis)
• Skin rash like severe sunburn which can occur on skin that has previously been exposed to radiotherapy (radiation recall)
• Scarring of the air sacs of the lung associated with radiation therapy (radiation toxicity)

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

• Increased platelet count (thrombocytosis)
• Severe rash with itching, blistering or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Inflammation of the lining of the large bowel, caused by reduced blood supply (ischaemic colitis)
• Clots forming in small blood vessels (thrombotic microangiopathy)

Not known: frequency cannot be estimated from the available data

• When bacteria and their toxins circulate in the blood and start to damage the organs (sepsis)
• Skin redness with swelling (pseudocellulitis)

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 at: or search for MHRA Yellow Card in the Google Play or Apple App Store.

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

5. how to store gemcitabine

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

Do not use this medicine after the expiry date which is stated on the carton after EXP.

This medicinal product does not require any special storage conditions.

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 35 days at 25 °C. Further dilution by a healthcare professional may be done. Solutions of reconstituted gemcitabine should not be refrigerated, as crystallisation may occur.

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

6. contents of the pack and other information

What Gemcitabine contains

• – The active substance is gemcitabine. Each vial contains 200, 1,000 or 1,500 mg of gemcitabine (as gemcitabine hydrochloride).

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