Gemcitabine 100 mg/ml Concentrate for Solution for – patient leaflet, side effects, dosage

1. What Gemcitabine Concentrate for solution for infusion is and what it is used for

The name of your medicine is ‘Gemcitabine 100 mg/ml Concentrate for Solution for Infusion’ but in the rest of the leaflet it will be called ‘Gemcitabine concentrate for solution for infusion’.

Gemcitabine Concentrate for solution for infusion belongs to a group of medicines called “cytotoxics”. These medicines kill dividing cells, including cancer cells.

Gemcitabine Concentrate for solution for infusion may be given alone or in combination with other anti-cancer medicines, depending on the type of cancer.

Gemcitabine Concentrate for solution for infusion 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 Concentrate for solution for infusion

You should not be given Gemcitabine Concentrate for solution for infusion

• if you are allergic (hypersensitive) to Gemcitabine or any of the other ingredients of Gemcitabine Concentrate for solution for infusion.
• if you are breast-feeding.

Take Special care with Gemcitabine Concentrate for solution for infusion

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 Concentrate for solution for infusion. 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 ever developed a severe skin rash or skin peeling, blistering and/or mouth sores after using gemcitabine.
• you have, or have previously had liver disease, heart disease, vascular disease or problems with your kidneys.
• 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 or a problem with your lungs).
• you are suffering from alcoholism, as this medicinal product contains ethanol (alcohol)
• you are suffering from epilepsy, as this medicinal product contains ethanol (alcohol).
• you develop symptoms such as headaches with confusion, convulsions (epileptic seizures) or visual disturbances (may be sign of very rare neurological side effect called posterior reversible encephalopathy syndrome).
• you develop generalised oedema, shortness of breath or weight gain (may be sign of fluid leaking from your small blood vessels into the tissues).

Serious skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis (AGEP) have been reported in association with gemcitabine treatment. Seek medical attention immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.

Men are advised not to father a child during and up to 6 months following treatment with Gemcitabine Concentrate for solution for infusion. 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 Concentrate for solution for infusion should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Gemcitabine Concentrate for solution for infusion during pregnancy. Women of childbearing potential must use effective contraception during treatment with Gemcitabine Concentrate for solution for infusion and for 6 months after the last administration.

If you are breast-feeding, tell your doctor.

You must discontinue breast-feeding during Gemcitabine Concentrate for solution for infusion treatment.

Fertility

Men are advised not to father a child during their treatment with Gemcitabine concentrate for solution for infusion and for3 months after its discontinuation, and consequently to use effective contraception during their treatment with Gemcitabine concentrate for solution for infusion and for 3 months after its discontinuation. If you would like to father a child during the

treatment or with in 3 months following treatment, seek advice from your doctor or pharmacist. You can seek advice on sperm storage before starting your therapy.

Driving and using machines

Gemcitabine Concentrate for solution for infusion may make you feel sleepy, particularly if you have consumed any alcohol. The amount of alcohol in this medicinal product may impair your ability to drive or use machines. Do not drive a car or use machinery until you are sure that treatment with Gemcitabine has not made you feel sleepy.

Important information about some of the ingredients of Gemcitabine

This medicine contains ethanol anhydrous 44 % w/v, i.e. up to 9.9 g per maximum daily dose (2250 mg), equivalent to 250 ml beer or 100 ml wine per dose.

• Harmful for those suffering from alcoholism.
• To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.
• The amount of alcohol in this medicinal product may alter the effects of other medicines.
• The amount of alcohol in this medicinal product may impair your ability to drive or use machines.

This medicine contains 199.6 mg (8.68 mmol) of sodium per maximum daily dose (2250 mg). To be taken into consideration by patients on a controlled sodium diet.

3. How Gemcitabine Concentrate for solution for infusion is given

The usual dose of Gemcitabine Concentrate for solution for infusion 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 Concentrate for solution for 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, Gemcitabine Concentrate for solution for infusion can cause side effects, although not everybody gets them.

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

• If you have a temperature of 38⁰C 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, which is common).

The following information is intended for medical or healthcare professionals only

Instructions for use, handling and disposal.

1. 1) Use aseptic techniques during preparation of gemcitabine for intravenous infusion administration.
2. 2)

   Calculate the dose and the number of Gemcitabine vials needed.

   Gemcitabine concentrate for solution for infusion is a clear colourless to slightly yellow solution with a concentration of 100 mg/ml gemcitabine. The concentrate should be diluted with sterile sodium chloride 9 mg/ml (0.9%) solution for injection, without preservative to a final concentration of 0.1 to 10 mg/ml.

   The total quantity of the Gemcitabine concentrate for solution for infusion required for an individual patient should be diluted into at least 250 ml of diluent. Further dilution with the same diluent can be done. Diluted solution is a clear colourless to slightly yellow solution.

   1. 3) After opening before dilution:

Each vial is for single use and should be used immediately after opening. If not used immediately, in-use storage times and conditions are the responsibility of the user.

After dilution:

Chemical and physical in-use stability after dilution in 0.9 % sodium chloride solution has been demonstrated for 3 days at 25°C and 2 °C to 8 °C.

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 condition.

Preparation of the infusion solution

Gemcitabine concentrate for solution for infusion should be diluted prior to administration.

If the vials are stored under refrigeration, allow the required number of boxes of Gemcitabine concentrate for solution for infusion to stand below 25°C for 5 minutes before use. More

INP161 10 3584 2 6028880

• Irregular heart rate (arrhythmia) (uncommon).
• Pain, redness, swelling or sores in your mouth (stomatitis) (common).
• Mild to moderately severe skin rash (very common) / itching (common), or fever (very common) (allergic reactions).
• 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).
• 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. These may be features of thrombotic microangiopathy (clots forming in small blood vessels) and haemolytic uraemic syndrome, which may be fatal.
• Severe chest pain (myocardial infarction) (rare).
• A severe hypersensitivity/allergic reaction with severe skin rash, including reddening of the skin and itching, swelling of the hands, feet, ankles, face, lips, mouth or throat (which can cause swallowing or breathing difficulties), wheezing, rapid heartbeat and feeling faint (anaphylactic reaction) (very rare).
• Generalised oedema, shortness of breath or weight gain, as fluid could leak from your small blood vessels into tissues (capillary leak syndrome) (very rare).
• Headaches with visual disturbances, confusion, convulsions or epileptic seizures (posterior reversible encephalopathy syndrome) (very rare).
• A severe skin rash with itching, bullous lesions or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• A red, scaly widespread rash with bumps under the swollen skin (including your skin folds, trunk, and upper extremities) and blisters accompanied by fever (Acute Generalized Exanthematous Pustulosis (AGEP)) (frequency not known).

Other side effects

Very common (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). Common (may affect up to 1 in 10 people)
• Poor appetite (anorexia)
• Headache
• Insomnia
• Sleepiness
• Cough
• Runny nose
• Constipation
• Diarrhoea
• Itching
• Excessive sweating
• Muscle pain
• Back pain
• Fever
• Feeling weak
• Chills

• Infections.

  Uncommon (may affect up to 1 in 100 people)

  • Alveolar lung lesions (interstitial lung disease).Noisy breathing (spasm of the airways)
  • Abnormal chest X ray/scan (lung lesions)
  • Heart failure
  • Serious liver damage, including liver failure
  • Kidney failure
  • Cerebrovascular accident

Rare (may affect up to 1 in 1000 people)

• Low blood pressure
• Skin scaling, ulceration or blister formation
• Injection site reactions
• Alveolar lung damage associated with radiotherapy (toxicity associated with radiation).
• Gangrene of fingers or toes
• Fluid in the lungs
• Severe lung inflammation resulting in respiratory failure (adult respiratory distress syndrome).
• Radiation recall (a skin rash like severe sunburn) which can occur on skin that has previously been exposed to radiotherapy (recall reactions).
• Radiation toxicity: scarring of the air sacs of the lung associated with radiation therapy
• Inflammation of the blood vessels (peripheral vasculitis).

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

• Increased platelet count
• Ischaemic colitis (inflammation of the lining of the large bowel, caused by reduced blood supply)
• A low haemoglobin level (anaemia) and low white blood cell and platelet counts will be detected by blood sampling
• Thrombotic microangiopathy: clots forming in small blood vessels

Not known (frequency cannot be estimated from the available data)

• Sepsis: when bacteria and their toxins circulate in the blood and starts to damage the organs
• Pseudo cellulitis: Skin redness with swelling

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.

Reporting of side effects

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

This medicinal product does not require any special storage conditions.

After opening before dilution:

Each vial is for single use and should be used immediately after opening. If not used immediately, in-use storage times and conditions are the responsibility of the user.

After dilution:

Chemical and physical in-use stability after dilution in 0.9 % sodium chloride solution has been demonstrated for 3 days at 25°C and 2 °C to 8 °C.

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 condition.

This medicine will be prepared and administered to you by healthcare staff. Any unused medicine must be disposed of by the healthcare staff.

6. Further information

What Gemcitabine Concentrate for solution for infusion contains:

Gemcitabine concentrate for solution for infusion contains the active ingredient Gemcitabine.

Each ml of the concentrate for solution for infusion contains 100 mg gemcitabine (as gemcitabine hydrochloride).

Each vial contains either 200 mg, 1000 mg, 1500 mg or 2000 mg gemcitabine (as gemcitabine hydrochloride).

The other ingredients are Macrogol 300, Propylene Glycol, Sodium Hydroxide and Ethanol anhydrous.

What Gemcitabine Concentrate for solution for infusion looks like and contents of the pack

This medicine is a concentrate for solution for infusion. The concentrate is a clear, colourless to slightly yellow solution. It is filled in clear glass vials sealed with rubber stoppers and aluminium flip-off seals.

Pack sizes:

Each vial of 2 ml contains 200 mg gemcitabine.

Each vial of 10 ml contains 1000 mg gemcitabine. Each vial of 15 ml contains 1500 mg gemcitabine. Each vial of 20 ml contains 2000 mg gemcitabine

Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Accord Healthcare Limited

Sage House, 319 Pinner Road, North Harrow,

Middlesex, HA1 4HF

United Kingdom

Manufacturer:

Accord Healthcare Limited

Sage House, 319 Pinner Road, North Harrow,

Middlesex, HA1 4HF

United Kingdom

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice, Poland

This leaflet was last approved in 02/2024.

than one vial of Gemcitabine concentrate for solution for infusion may be necessary to obtain the required dose for the patient.

Aseptically withdraw the required amount of Gemcitabine concentrate for solution for infusion using a calibrated syringe. The required volume of Gemcitabine concentrate for solution for infusion must be injected into at least 250 ml infusion bag containing sodium chloride 9 mg/ml (0.9%) solution for infusion.

Mix the infusion bag manually using a rocking motion. Further dilution with the same diluent can be done.

The infusion bag solution should be used within 24 hours when stored at 2°-8° C. As with all parenteral medicinal products,

Gemcitabine infusion solution should be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, do not administer.

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