GEMCITABINE AUROVITAS SPAIN 2000 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Gemcitabina Aurovitas Spain 2,000 mg concentrate for solution for infusion

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, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Gemcitabina Aurovitas Spain is and what it is used for

Gemcitabina Aurovitas Spain belongs to a group of medicines called “cytotoxics”. These medicines destroy cells that are dividing, including cancer cells.

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

Gemcitabine 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 Gemcitabina Aurovitas Spain

Do not useGemcitabina Aurovitas Spain

• 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

Before the first infusion, blood samples will be taken to check if your liver and kidneys are working well enough to receive this medicine. Also, before each infusion, blood samples will be taken to check if you have enough red blood cells to receive gemcitabine. Your doctor may decide to change the dose or delay treatment depending on your general health and if your blood cell counts are too low. Periodically, blood samples will be taken to check how your kidneys and liver are working.

Talk to your doctor, nurse, or hospital pharmacist before you start using this medicine.

If you have ever developed a severe skin rash or skin peeling, blisters, and/or sores in the mouth after using gemcitabine.

If you have or have had liver, heart, blood vessel, or kidney disease, talk to your doctor or hospital pharmacist, as you may not be able to receive gemcitabine.

Tell your doctor if you have recently received or are going to receive radiotherapy, as gemcitabine can cause an early or late reaction to radiation.

Tell your doctor if you have been vaccinated recently, as this can cause negative effects with gemcitabine.

If during treatment with this medicine you have symptoms such as headache with confusion, seizures, 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.

Tell your doctor if you have difficulty breathing or feel very weak and are very pale, as this may be a sign of kidney failure or problems with your lungs.

Tell your doctor if you have swelling, shortness of breath, or weight gain, as these may be signs of fluid leakage from your small blood vessels to your tissues.

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 medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents

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

Other medicines and Gemcitabina Aurovitas Spain

Tell your doctor or hospital pharmacist if you are taking, have recently taken, or might take any other medicines, including vaccines and medicines obtained without a prescription, or if you have received or are going to receive radiotherapy.

Pregnancy, breast-feeding, and fertility

Pregnancy

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. The use of gemcitabine should be avoided during pregnancy. Your doctor will discuss with you the potential risk of using gemcitabine during pregnancy. Women of childbearing age must use an effective method of contraception during treatment with gemcitabine and for 6 months after the last administration.

Breast-feeding

Tell your doctor if you are breast-feeding.

You must stop breast-feeding during treatment with gemcitabine.

Fertility

Men are advised not to father a child during treatment with gemcitabine and for 3 months after treatment. If you wish to father a child during treatment and 3 months after treatment, ask your doctor or pharmacist for advice. You may request information on sperm preservation before starting your treatment.

Driving and using machines

Gemcitabine may cause drowsiness.

Do not drive or use machines until you are sure that treatment with gemcitabine does not make you drowsy.

3. How to use Gemcitabina Aurovitas Spain

The recommended dose of gemcitabine is 1,000-1,250 mg per square meter of your body surface area. Your height and weight are 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 blood cell counts.

The frequency at which you receive your gemcitabine infusion depends on the type of cancer you are being treated for.

A hospital pharmacist or doctor will have diluted the Gemcitabina Aurovitas Spain concentrate before it is given to you.

You will always receive this medicine by infusion into one of your veins. The infusion will take approximately 30 minutes.

This medicine is not recommended for use in children under 18 years.

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:

• Bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, unexpected bruising (as you may have fewer platelets than normal, which is very common).
• Tiredness, feeling faint, getting breathless easily, or if you are pale (as you may have less hemoglobin than normal, which is very common).
• Allergic reactions: mild or moderate skin rash (very common), itching (common), or fever (very common).
• Temperature of 38°C or higher, sweating, or other signs of infection (as you may have fewer white blood cells than normal, accompanied by fever, also known as febrile neutropenia) (common).
• Pain, redness, swelling, or sores in the mouth (stomatitis) (common).
• Irregular heartbeat (arrhythmia) (uncommon).
• Extreme weakness and tiredness, purpura, or small areas of bleeding in the skin (hematomas), acute kidney failure (low urine production or absence of urine production), and signs of infection (hemolytic uremic syndrome). This can be fatal (uncommon).
• Difficulty breathing (it is common to have mild difficulty breathing immediately after gemcitabine infusion, which passes soon; however, uncommonly or rarely, there can be more serious lung problems).
• Severe chest pain (myocardial infarction) (rare).
• Severe allergic reaction/hypersensitivity reaction, with severe skin rash, including redness and itching of the skin, swelling of hands, feet, ankles, face, lips, mouth, or throat (which can cause difficulty swallowing or breathing), wheezing, rapid heartbeat (tachycardia), and you may feel like you are going to faint (anaphylactic reaction) (very rare).
• Generalized swelling, shortness of breath, or weight gain, as you may have fluid leakage from your small blood vessels to your tissues (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures, or convulsions (posterior reversible encephalopathy syndrome) (very rare).
• Severe rash with itching, blisters, or skin peeling, often accompanied by symptoms similar to those of the flu (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Extreme tiredness and weakness, purpura, or small areas of bleeding in the skin (hematomas), acute kidney injury (low urine production or absence of urine production), and signs of infection. These can be signs of thrombotic microangiopathy (blood clots forming in small blood vessels) and hemolytic uremic syndrome, which can be fatal.
• 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).

Other side effects with gemcitabine may include:

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

Low white blood cell count

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)

Low hemoglobin level (anemia)

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

Poor appetite (anorexia)

Headache

Insomnia

Drowsiness

Cough

Stuffy nose

Constipation

Diarrhea

Itching

Sweating

Muscle pain

Back pain

Fever

Weakness

Chills

Infections

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

Hardening of the walls of the lung air sacs (interstitial pneumonitis)

Wheezing (bronchospasm)

Hardening of the walls of the lungs (abnormal chest X-ray/scan)

Heart failure

Kidney failure

Severe liver damage, including liver failure, which can be potentially fatal

Stroke (cerebral infarction)

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

Low blood pressure

Peeling of the skin, ulcers, or blisters

Severe peeling of the skin and blisters on the skin

Reactions at the injection site

Severe lung inflammation causing respiratory failure (adult respiratory distress syndrome)

Severe skin rash similar to sunburn, which can occur in skin previously exposed to radiotherapy (late radiation toxicity)

Fluid in the lungs

Hardening of the walls of the lung air sacs associated with radiotherapy (radiation-associated toxicity)

Gangrene of the toes or fingers

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 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.

Thrombotic microangiopathy: blood clots forming in small blood vessels.

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

Sepsis: when bacteria and their toxins circulate in your blood and start damaging your organs.

Pseudo-cellulitis: Redness of the skin with swelling.

You may have any of these symptoms and/or conditions. You should tell your doctor as soon as possible if you start experiencing any of these side effects.

Reporting of side effects

If you experience 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 to the Spanish Medicines Surveillance System for Human Use: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Gemcitabina Aurovitas Spain

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

Unopened vial

Store in a refrigerator (between 2°C and 8°C).

After first opening:

Physical and chemical stability has been demonstrated for 28 days at 25°C.

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

Infusion solution:

Chemical and physical stability has been demonstrated for 28 days at 2-8°C and approximately 25°C after dilution in a 0.9% sodium chloride solution to a final concentration in the range of 2 to 25 mg/ml (2.0 mg/ml, 12 mg/ml, and 25 mg/ml). The diluted solutions are stable when stored in PVC or PE infusion bags.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

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

Do not use this medicine if you notice particles.

6. Container contents and additional information

Composition ofGemcitabina Aurovitas Spain

• The active ingredient is gemcitabine (as gemcitabine hydrochloride). Each ml of concentrate for solution for infusion contains 40 mg of gemcitabine (as gemcitabine hydrochloride).

Each 50 ml vial contains 2,000 mg of gemcitabine (as gemcitabine hydrochloride).

• The other components are hydrochloric acid (E-507) for pH adjustment and water for injectable preparations.

Appearance of the product and container contents

Gemcitabina Aurovitas Spain concentrate for solution for infusion is a clear, colorless or pale yellow solution.

Gemcitabina Aurovitas Spain is presented in a colorless type I glass vial with a rubber stopper and closed with an aluminum cap with a polypropylene disc. The vial may be packaged with or without a protective plastic wrapper.

Container size

1 vial of 50 ml

Only some container sizes may be marketed.

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Date of last revision of this leaflet: December 2023

Other sources of information

Detailed 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

Gemcitabina Aurovitas Spain 2,000 mg concentrate for solution for infusion

Cytotoxic

Handling

To prepare or dispose of the infusion solution, standard safety precautions for cytostatic agents should be followed. Pregnant women should not handle the product. Handling of the solution should be performed in a safety cabinet and protective gowns and gloves should be used. If a safety cabinet is not available, the equipment should be supplemented with a mask and protective glasses.

If the product comes into contact with the eyes, it may cause severe irritation. The eyes should be rinsed immediately with a large amount of water. Consult a doctor if irritation persists. If the solution comes into contact with the skin, wash the affected area thoroughly with plenty of water.

Dilution instructions

The only approved solvent for dilution of Gemcitabina Aurovitas Spain concentrate for solution for infusion is a 9 mg/ml (0.9%) sodium chloride injection solution (without preservatives).

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

• The diluted solution is a clear, colorless or pale yellow solution.

• Parenteral drugs should be inspected visually for particles or discoloration before administration. If particles are observed, the solution should not be administered.

• Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Storage conditions

After first opening:

Physical and chemical stability has been demonstrated for 28 days at 25°C.

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

Infusion solution:

Chemical and physical stability has been demonstrated for 28 days at 2-8°C and approximately 25°C after dilution in a 0.9% sodium chloride solution up to a final concentration in the range of 2 to 25 mg/ml (2.0 mg/ml, 12 mg/ml, and 25 mg/ml). The pH of the diluted solution is in the range of 2-3 and the osmolarity is approximately 285 mOsm/kg. The diluted solutions are stable when packaged in PVC or PE infusion bags.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has taken place in controlled and validated aseptic conditions.