GEMCITABINE SUN 1000 mg POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Gemcitabine SUN 1000 mg powder for solution for infusion EFG

Gemcitabine

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

Contents of the pack

1. What Gemcitabine SUN is and what it is used for
2. What you need to know before you use Gemcitabine SUN
3. How to use Gemcitabine SUN
4. Possible side effects
5. Storage of Gemcitabine SUN
6. Contents of the pack and other information

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

Gemcitabine SUN is a medicine used to treat cancer. It belongs to a group of medicines called "cytotoxics". These medicines destroy cells that are dividing, including cancer cells.

Gemcitabine SUN can be given alone or in combination with other anti-cancer medicines, depending on the type of cancer.

Gemcitabine SUN is used to treat the following types of cancer:

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

2. What you need to know before you use Gemcitabine SUN

Do not use Gemcitabine SUN:

• if you are allergic to gemcitabine or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding, you must stop breast-feeding before starting treatment with Gemcitabine SUN.

Warnings and precautions

Consult your doctor before starting treatment with Gemcitabine SUN.

Before the first infusion, blood samples will be taken to check if your liver and kidney function are normal. Also, before each infusion, blood samples will be taken to check if you have enough red blood cells to receive Gemcitabine SUN. Your doctor may decide to change the dose or delay treatment depending on your general condition and if your blood cell counts are too low. Periodically, blood samples will be taken to check the function of your kidneys and liver.

Tell your doctor if:

• you have or have had liver, heart, blood vessel, or kidney disease, as you may not be able to receive Gemcitabine SUN.
• you have recently received or are going to receive radiotherapy, as Gemcitabine SUN may cause an early or late reaction to radiation.
• you have been vaccinated recently.
• you experience symptoms such as headache with confusion, seizures (epileptic fits), or changes in vision, consult your doctor immediately. This could be a very rare side effect of the nervous system called posterior reversible encephalopathy syndrome.
• you have difficulty breathing or feel very weak and are very pale, as this may be a sign of kidney failure or lung problems.
• you have swelling, shortness of breath, or weight gain, as this may be a sign of fluid leaking from your small blood vessels into your tissues.
• you have developed a severe skin rash or skin peeling, blisters, and/or sores in the mouth after using gemcitabine.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP), have been reported in association with gemcitabine treatment. Seek immediate medical attention if you observe any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents

The use of this medicine is not recommended in children under 18 years due to lack of safety and efficacy data in this population.

Using Gemcitabine SUN with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. The use of Gemcitabine SUN should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Gemcitabine SUN during pregnancy.

You must stop breast-feeding during treatment with Gemcitabine SUN.

Men are advised not to father a child during treatment with Gemcitabine SUN and for 6 months after treatment. If you wish to father a child during treatment or in the 6 months after treatment, consult your doctor or pharmacist. You may want to seek advice on sperm conservation before starting treatment.

Driving and using machines

Gemcitabine SUN may cause drowsiness, especially if you have consumed alcohol. Avoid driving or using machines until you are sure that treatment with Gemcitabine SUN does not make you drowsy.

Gemcitabine SUN contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, which is essentially "sodium-free".

3. How to use Gemcitabine SUN

The recommended dose of Gemcitabine SUN is 1,000-1,250 mg per square meter of your body surface area. Your height and weight will be measured to calculate the area of your body. Your doctor will use this body surface area to calculate the correct dose for you. This dose may be adjusted or treatment delayed depending on your general health and your blood cell counts.

The frequency at which you receive your Gemcitabine SUN infusion depends on the type of cancer being treated.

A hospital pharmacist or doctor will have dissolved the Gemcitabine SUN powder before it is given to you.

You will always receive Gemcitabine SUN by infusion into one of your veins. The infusion will take about 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.

Contact your doctor immediately if you notice any of the following:

Extreme tiredness and weakness, bruising, or small bleeding spots under the skin (petechiae), acute kidney injury (low urine output or no urine output), and signs of infection. These may be signs of thrombotic microangiopathy (blood clots forming in small blood vessels) and hemolytic uremic syndrome, which can be fatal.

A red, scaly, and widespread rash with bumps under the inflamed skin (including skin folds, trunk, and upper limbs) and blisters accompanied by fever (acute generalized exanthematous pustulosis (AGEP)) (frequency not known).

You must contact your doctor immediately if you observe any of the following serious side effects:

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

• allergic reactions: if you experience a mild to moderate skin rash or fever
• fatigue, feeling faint, getting breathless easily, or if you are pale (as you may have lower than normal hemoglobin levels, which is very common)
• bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, unexpected bruising (as you may have lower than normal platelet levels, which is very common).

Common (may affect up to 1 in 10 people)

• temperature of 38°C or higher, sweating, or other signs of infection (as you may have lower than normal white blood cell counts accompanied by fever, also known as febrile neutropenia).
• pain, redness, swelling, or ulcers in the mouth (stomatitis).
• allergic reactions: if you experience itching, difficulty breathing (it is common to have mild difficulty breathing immediately after Gemcitabine SUN infusion, which passes soon).

Uncommon:may affect up to 1 in 100 people

• difficulty breathing (more serious lung problems)
• irregular heartbeat (arrhythmia)

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

• difficulty breathing (more serious lung problems)
• severe chest pain (myocardial infarction)

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

• severe allergic reaction with severe skin rash, including red, swollen, blistered, or peeling skin, and blisters accompanied by fever (anaphylactic reaction)
• widespread swelling, shortness of breath, or weight gain, as you may have fluid leaking from your small blood vessels into your tissues (capillary leak syndrome)
• headache with changes in vision, confusion, seizures, or fits (posterior reversible encephalopathy syndrome)
• severe skin rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

Frequency not known (cannot be estimated from the available data)

• generalized red and scaly rash with bumps under the inflamed skin (including skin folds, trunk, and upper limbs) and blisters accompanied by fever (acute generalized exanthematous pustulosis (AGEP)) (frequency not known).

Tell your doctor if you notice any of the following side effects:

Very common:may affect more than 1 in 10 people

• low white blood cell count in the blood, difficulty breathing
• vomiting
• nausea
• hair loss
• liver problems: identified through abnormal blood test results
• blood in the urine
• abnormal urine tests: protein in the urine
• pseudo-flu syndrome, including fever
• swelling of the ankles, fingers, feet, face (edema)

Common:may affect up to 1 in 10 people

• loss of appetite (anorexia)
• headache
• insomnia
• drowsiness
• cough
• runny nose
• constipation
• diarrhea
• itching
• sweating
• muscle pain
• back pain
• fever
• weakness
• chills
• infections

Uncommon:may affect up to 1 in 100 people

• scarring of the lungs (interstitial pneumonitis)
• wheezing (bronchospasm)
• scarring of the lung tissue (abnormal chest X-ray/scan)
• heart failure
• kidney failure
• severe liver damage, including liver failure
• stroke (cerebral infarction)

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

• low blood pressure
• skin peeling, ulceration, or blistering
• severe skin peeling and blistering
• reactions at the injection site
• severe lung inflammation causing respiratory failure (adult respiratory distress syndrome)
• severe sunburn-like skin rash that can occur in skin previously exposed to radiotherapy (radiation-induced dermatitis)
• fluid in the lungs
• scarring of the lung tissue associated with radiotherapy (radiation-induced toxicity)
• gangrene of the toes or fingers
• inflammation of the blood vessels (peripheral vasculitis)

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

• increased platelet count
• inflammation of the lining of the large intestine, caused by reduced blood supply (ischemic colitis)

• through a blood test, it will be detected if there are low levels of hemoglobin (anemia), low white blood cell count, and low platelet count.
• blood clots forming in small blood vessels (thrombotic microangiopathy).

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

• sepsis: when bacteria and their toxins circulate in your blood and start damaging your organs

• redness of the skin with swelling (pseudocellulitis).
• A condition in which eosinophils, a type of cell that is normally found in the blood, accumulate in the lungs (pulmonary eosinophilia).

Reporting of side effects

If you experience 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 Spanish Medicines Agency's website: www.notificaRAM.es.

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

5. Storage of Gemcitabine SUN

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 vial and carton. The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

After reconstitution:

Chemical and physical stability in use has been demonstrated for 24 hours at 30°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and normally should not be longer than 24 hours at 30°C.

The reconstituted solution should not be refrigerated.

Do not use this medicine if you notice that the solution is cloudy or if you notice any precipitate.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Contents and Additional Information

Composition of Gemcitabine SUN 1,000 mg powder for solution for infusion EFG

• The active ingredient is: gemcitabine (as hydrochloride)
• The other components are: mannitol, sodium acetate trihydrate, sodium hydroxide, hydrochloric acid.

A vial contains 1g of gemcitabine (as hydrochloride).

1 ml of the reconstituted solution for infusion contains 38 mg of gemcitabine (as hydrochloride).

Product Appearance and Container Contents

Powder for solution for infusion

White or off-white lyophilized cake powder.

1 vial of 50 ml.

Marketing Authorization Holder and Manufacturer

SUN Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

Local Representative

Sun Pharma Laboratories, S.L.

Rambla de Catalunya, 53-55

08007-Barcelona

Spain

Tel: +34 93 342 78 90

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Germany: Gemcitabine SUN 1,000 mg Powder for solution for infusion

Spain: Gemcitabina SUN 1,000 mg powder for solution for infusion EFG

Italy: Gemcitabina SUN 1,000 mg powder for solution for infusion

Netherlands: Gemcitabine SUN 1,000 mg powder for solution for infusion

Romania: Gemcitabina SUN 1,000 mg powder for solution for infusion

United Kingdom (Northern Ireland): Gemcitabine 1,000 mg Powder for Solution for Infusion

Date of the last revision of this leaflet:February 2024.

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

This information is intended only for healthcare professionals:

Instructions for use, handling, and disposal

• Use aseptic techniques during the reconstitution and any subsequent dilution of gemcitabine for administration by intravenous infusion.
• Calculate the dose and the number of vials of Gemcitabine SUN needed.
• Reconstitute each 1,000 mg vial with 25 ml of sterile sodium chloride injection solution, 9 mg/ml (0.9%), without preservatives. Shake to dissolve. The total volume after reconstitution is 26.3 ml. The resulting concentration of gemcitabine from this dilution is 38 mg/ml, considering the displacement volume of the lyophilized powder. It can be further diluted with a sodium chloride injection solution, 9 mg/ml (0.9%), without preservatives. The reconstituted solution is a clear, colorless or pale yellow solution.
• Before administration, the medicinal products must be visually inspected for potential particles in suspension and/or discoloration. If particles are observed, the product should not be administered.
• The reconstituted gemcitabine solutions should not be refrigerated as crystallization may occur. Chemical and physical stability has been demonstrated for 24 hours at 30°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage conditions and periods before use will be the responsibility of the user and should not exceed 24 hours at a temperature below 30°C, unless the reconstitution/dilution is carried out under controlled and validated aseptic conditions.
• Gemcitabine solutions should be used once only. Any unused or waste product should be disposed of in accordance with local regulations.

Precautions for preparation and administration

Normal safety precautions for cytostatic agents should be taken into account when preparing and disposing of the infusion solution. Handling of the solution should be carried out in a safety cabinet, and protective clothing and gloves should be worn. If a safety cabinet is not available, the equipment should be supplemented with masks and eye protection.

If the preparation comes into contact with the eyes, it may cause severe irritation. The eyes should be rinsed immediately and thoroughly with plenty of water. If irritation persists, a doctor should be consulted. If the solution spills on the skin, it should be rinsed thoroughly with plenty of water.

Disposal

Any unused product should be disposed of in accordance with local regulations.