GEMCITABINE ACCORD 1000 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Gemcitabine Accord 1,000 mg concentrate for solution for infusion

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack:

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

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

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

Gemcitabine Accord 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 Accord

Do not use Gemcitabine Accord:

• If you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• If you are breast-feeding, you must stop breast-feeding during treatment with Gemcitabine Accord.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Gemcitabine Accord.

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 Accord. 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 ever developed a severe skin rash or peeling of the skin, blisters, and/or sores in the mouth after using gemcitabine.
• you have or have had liver, heart, blood vessel disease, or kidney problems.
• you have recently received or are going to receive radiotherapy, as there may be an early or late radiation reaction with gemcitabine.
• you have been vaccinated recently, as this may cause negative effects with gemcitabine.
• during treatment with this medicine, you experience symptoms such as headache with confusion, seizures, or changes in vision, call 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 very pale (may be a sign of lung or kidney failure).
• you have a history of alcoholism, as this medicine contains ethanol (alcohol).
• you have epilepsy, as this medicine contains ethanol (alcohol).
• you experience capillary leak syndrome (CLS), when fluids from small blood vessels leak into tissues. Symptoms may include swelling of the legs, face, and arms, weight gain, low protein levels in the blood, severe low blood pressure, acute kidney failure, and pulmonary edema.
• you experience posterior reversible encephalopathy syndrome (PRES). Symptoms include decreased level of consciousness, seizures, headache, visual disturbances, focal neurological signs, and acute elevation of blood pressure.

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 of age due to lack of data on safety and efficacy.

Interaction of Gemcitabine Accord with other medicines

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

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 or pharmacist for advice before using this medicine.

The use of Gemcitabine Accord should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Gemcitabine Accord during pregnancy. Women of childbearing potential must use an effective method of contraception during treatment with Gemcitabine Accord and for 6 months after the last administration.

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

Fertility

Men are advised not to father a child during treatment with Gemcitabine Accord and for 3 months after treatment. Consequently, men should use a effective method of contraception during treatment with Gemcitabine Accord and for 3 months after treatment. If you wish to father a child during treatment or in the 3 months after treatment, seek advice from your doctor or pharmacist. You may want to ask for information on sperm conservation before starting treatment.

Driving and using machines

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

Gemcitabine Accord contains 44% ethanol (alcohol), which corresponds to a maximum amount of 9.9 g per dose, equivalent to 250 ml of beer or 100 ml of wine.

This medicine is harmful to individuals with alcoholism.

The alcohol content should be taken into account in the case of pregnant or breast-feeding women, children, and high-risk groups, such as patients with liver disease or epilepsy.

The amount of alcohol in this medicine may alter the effects of other medicines.

The amount of alcohol in this medicine may impair your ability to drive or operate machinery.

Gemcitabine Accord contains sodium.Patients on low-sodium diets should be aware that this medicine contains 206 mg (9.0 mmol) of sodium per maximum daily dose (2,250 mg).

3. How to use Gemcitabine Accord

The recommended dose is 1,000 - 1,250 mg per square meter of 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 blood cell counts.

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

A hospital pharmacist or doctor will have diluted the Gemcitabine Accord concentrate before it is administered to you.

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

This medicine is not recommended for children under 18 years of age.

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

4. Possible side effects

Like all medicines, Gemcitabine Accord can cause side effects, although not everybody gets them.

You should contact your doctor immediately if you develop any of the following:

Bleeding from the gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, unexpected bruising (as you may have a lower than normal platelet count, which is very common).

Feeling tired, faint, or short of breath, or if you are pale (as you may have lower than normal hemoglobin levels, which is very common).

Mild or moderate skin rash (very common) / itching (common), or fever (very common); allergic reactions.

Temperature of 38°C or higher, sweating, or other signs of infection (as you may have a lower than normal white blood cell count, accompanied by fever, also known as febrile neutropenia, which is common).

Pain, redness, swelling, or sores in the mouth (stomatitis) (common).

Irregular heartbeat (arrhythmia) (uncommon).

Extreme fatigue and weakness, purple spots, and small areas of bleeding under the skin (petechiae), acute kidney failure (little or no urine production), and signs of infection. These may be signs of hemolytic uremic syndrome, which can be fatal (uncommon).

Difficulty breathing (it is very common to have mild difficulty breathing immediately after Gemcitabine Accord infusion, which passes quickly; however, uncommonly or rarely, there may be more serious lung problems).

Severe chest pain (myocardial infarction) (rare).

Severe allergic reaction with severe skin rash, including itching and redness, swelling of hands, feet, ankles, face, lips, mouth, and throat (which can cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and you may feel like you are going to faint (anaphylactic reaction) (very rare).

Generalized swelling, difficulty breathing, or weight gain, as you may have fluid leaking from small blood vessels into tissues (capillary leak syndrome) (very rare).

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

Severe skin rash with itching, blistering, or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).

• Extreme fatigue and weakness, purple spots, and small areas of bleeding under the skin (petechiae), acute kidney failure (little or no urine production), and signs of infection. These may be signs of thrombotic microangiopathy (formation of blood clots in small blood vessels) and hemolytic uremic syndrome, which can be fatal.

Generalized skin rash, red and scaly, 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 of Gemcitabine Accord may include:

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

• Low white blood cell count

Breathing difficulties

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 ankles, fingers, feet, face (edema)

Common (may affect up to 1 in 10 people)

Lack of appetite (anorexia)

Headache

Insomnia

Drowsiness

Cough

Stuffy nose

Constipation

Diarrhea

Itching

Excessive sweating

Muscle pain

Back pain

Fever

Feeling weak

Chills

Infections

Uncommon (may affect up to 1 in 100 people)

Lung tissue damage (interstitial lung disease)

Noisy breathing (bronchospasm)

Lung damage (abnormal chest X-ray or scan)

Heart failure

Severe liver damage, including liver failure

Kidney failure

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

Low blood pressure

Peeling of the skin, ulcers, or blisters on the skin

Reactions at the injection site

• Formation of large blisters on the skin or exudation of the skin

Gangrene of the fingers or toes

Fluid in the lungs

Severe lung inflammation leading to respiratory failure (adult respiratory distress syndrome).

Severe skin burn-like reaction that can occur in skin previously exposed to radiotherapy (radiation-induced skin toxicity).

Lung tissue damage associated with radiotherapy (radiation-induced lung injury).

Inflammation of blood vessels (peripheral vasculitis).

Elevated liver enzymes (GGT)

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

Increased platelet count

Inflammation of the large intestine, caused by reduced blood supply (ischemic colitis).

Thrombotic microangiopathy: formation of blood clots in small blood vessels. Low hemoglobin, low white blood cell count, and low platelet count will be detected through blood tests.

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

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

Pseudo-cellulitis: redness of the skin with swelling.

You may experience any of these symptoms and/or conditions. You should inform your doctor as soon as possible if you experience any of these side effects.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly to the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Gemcitabine Accord

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

This medicine does not require any special storage conditions.

After opening and before dilution:

Each vial is for single use and must be used immediately after opening. If not used immediately, the storage time and conditions will be the responsibility of the user.

After dilution:

After dilution in sodium chloride 0.9%, physical and chemical stability has been demonstrated for up to 60 days at 25°C and 2°C - 8°C.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the storage time and conditions will be the responsibility of the user and normally will not exceed 24 hours at 2°C - 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 carton after EXP. The expiry date refers to the last day of the month shown.

This medicine will be prepared and administered to you by healthcare personnel. Any unused medicine should be disposed of by healthcare personnel.

6. Container Contents and Additional Information

Gemcitabine Accord Contents

The active ingredient is gemcitabine. Each ml of concentrate for solution for infusion contains 100 mg of gemcitabine (as gemcitabine hydrochloride). Each vial contains 1000 mg of gemcitabine (as gemcitabine hydrochloride).

The other components (excipients) are macrogol 300, propylene glycol, anhydrous ethanol, sodium hydroxide (for pH adjustment), and concentrated hydrochloric acid (for pH adjustment).

Product Appearance and Container Contents

Gemcitabine Accord is a clear, colorless or slightly yellowish solution.

Gemcitabine Accord is packaged in a sealed glass vial with rubber stoppers and an aluminum flip-off seal.

Container Sizes

1 vial of 2 ml.

1 vial of 10 ml.

1 vial of 15 ml.

1 vial of 20 ml.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200

Pabianice,

Poland

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

Accord Healthcare Single Member S.A.

64th Km National Road Athens, Lamia, 32009, Greece

This medicinal product is authorized in the Member States of the European Economic Area under the following names

Date of Last Revision of this Leaflet: November 2024

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/

The following information is intended for healthcare professionals only:

Instructions for Use, Handling, and Disposal

Gemcitabine Accord requires proper dilution before use. The concentration of gemcitabine in Gemcitabine Accord differs from other gemcitabine products.

The concentration must be taken into account, or a life-threatening overdose may occur.

Gemcitabine Accord contains a higher concentration (100 mg/ml) than other gemcitabine products for intravenous infusion.

• Use aseptic techniques during the preparation of gemcitabine for intravenous infusion.

• Gemcitabine Accord is a clear, colorless or slightly yellowish solution with a concentration of 100 mg/ml of gemcitabine. The total amount of Gemcitabine Accord required for a patient must be diluted with sterile sodium chloride solution 9 mg/ml (0.9%). It can then be further diluted with the same diluent to a final concentration of approximately 0.1 to 9 mg/ml. Considering the maximum dose of ~2.25g for gemcitabine, the concentration of 4.5 mg/ml (achieved with 500 ml of diluent) to 9 mg/ml (achieved with 250 ml of diluent) corresponds to an osmolarity of approximately 1000 mOsmol/Kg to 1700 mOsmol/Kg.

• The storage of the diluted gemcitabine solution in plasticized polyvinyl chloride (PVC) containers may result in the leaching of DEHP (di-(2-ethylhexyl)phthalate); therefore, the preparation, storage, and administration of the diluted solution should be carried out using equipment that does not contain PVC.

Special Precautions for Storage

After opening and before dilution:

Each vial is for single use and must be used immediately after opening. If not used immediately, the conditions and periods of storage before use will be the responsibility of the user.

After dilution:

Chemical and physical stability has been demonstrated for 60 days at 25°C and 2°C - 8°C after dilution in 0.9% sodium chloride solution.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the conditions and periods of storage before use will be the responsibility of the user and should not exceed 24 hours at 2°C – 8°C, unless the dilution is carried out under controlled and validated aseptic conditions.

Preparation of the Infusion Solution

Gemcitabine Accord contains 100 mg of gemcitabine per ml of concentrated solution. The concentrated solution must be diluted before administration.

• If the vials are stored in the refrigerator, let the Gemcitabine Accord containers stand at below 25°C for 5 minutes before use. More than one vial of Gemcitabine Accord may be necessary to obtain the required dose for the patient.

• Using a calibrated syringe, aseptically withdraw the required amount of Gemcitabine Accord.

• The required volume of Gemcitabine Accord must be injected into an infusion bag with a sodium chloride solution for infusion 9 mg/ml (0.9%).

• Manually mix the infusion bag with an oscillating motion. It can then be further diluted with the same diluent to a final concentration of approximately 0.1 to 9 mg/ml. Considering the maximum dose of ~2.25g for gemcitabine, the concentration of 4.5 mg/ml (achieved with 500 ml of diluent) to 9 mg/ml (achieved with 250 ml of diluent) corresponds to an osmolarity of approximately 1000 mOsmol/Kg to 1700 mOsmol/Kg.

• As with all parenteral medicinal products, the gemcitabine infusion solution should be visually inspected before administration to avoid particle or discoloration problems. If particles are observed, do not administer.

Precautions for Preparation and Administration

Normal safety measures 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, consult a doctor. If the solution spills on the skin, rinse thoroughly with plenty of water.

Disposal

Disposal of the unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations.