Gemcitabine Accord 1500 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Gemcitabine Accord 1,500 mg concentrate for solution for infusion

Read the entire leaflet carefully before you start using this medicine.

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

Leaflet contents:

1. What Gemcitabine Accord is and what it is used for
2. What you need to know before using Gemcitabine Accord
3. How to use Gemcitabine Accord
4. Possible side effects
5. How to store 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 and belongs to a group of medicines called "cytotoxic agents". These medicines destroy dividing cells, including cancer cells.

Gemcitabine Accord may 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), either 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 using Gemcitabina Accord

Do not use Gemcitabina 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 breastfeeding, you must stop breastfeeding during treatment with Gemcitabina Accord.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Gemcitabina Accord.

Before the first infusion, blood samples will be taken to assess whether your liver and kidney function are normal. Similarly, blood samples will be taken before each infusion to evaluate whether you have enough red blood cells to receive Gemcitabina Accord. Your doctor may decide to adjust the dose or delay treatment depending on your general condition and whether your blood cell counts are too low. Blood samples will be taken periodically to monitor your kidney and liver function.

Inform your doctor if:

• You have ever developed a severe skin rash, skin peeling, blisters, and/or mouth sores after using gemcitabine.
• You currently have or have previously had liver, heart, blood vessel, or kidney problems.
• You have recently undergone or are scheduled to receive radiotherapy, as there may be an early or late radiation reaction when using gemcitabine.
• You have recently been vaccinated, as this could cause adverse effects with gemcitabine.
• During treatment with this medicine, you experience symptoms such as headache with confusion, seizures (fits), or changes in vision—contact your doctor immediately. This could be a very rare nervous system adverse effect known as reversible posterior encephalopathy syndrome.
• You experience difficulty breathing or feel very weak and pale (this could be a sign of lung problems or kidney failure).
• You suffer from alcoholism, as this medicine contains ethanol (alcohol).
• You suffer from epilepsy, as this medicine contains ethanol (alcohol).
• You experience capillary leak syndrome (CLS), in which fluids from small blood vessels leak into surrounding tissues. Symptoms may include swelling of the legs, face, and arms, weight gain, hypoalbuminemia (abnormally low levels of protein in the blood), severe hypotension (low blood pressure), acute kidney failure, and pulmonary edema (fluid in the lungs).
• You experience reversible posterior encephalopathy syndrome (RPES). Symptoms include decreased level of consciousness, seizures, headache, visual abnormalities, focal neurological signs, and acute elevation in 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 immediate medical attention if you notice any symptoms related to these severe skin reactions described in section 4.

Children and adolescents

Use of this medicine is not recommended in children under 18 years of age due to lack of data on safety and efficacy.

Interaction of Gemcitabina Accord with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including vaccines.

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

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

You must stop breastfeeding during treatment with Gemcitabina Accord.

Fertility

Men are advised not to father a child during treatment with Gemcitabina Accord and for 3 months after treatment ends. Therefore, an effective method of contraception should be used during treatment with Gemcitabina Accord and for 3 months after stopping treatment. If you wish to father a child during treatment or within 3 months after treatment ends, consult your doctor or pharmacist. You may wish to seek information about sperm preservation before starting treatment.

Driving and use of machines

Gemcitabina Accord may cause drowsiness, especially if alcohol has been consumed. Avoid driving or operating machinery until you are certain that treatment with Gemcitabina Accord does not cause drowsiness.

Gemcitabina Accord contains 44% ethanol (alcohol), corresponding to up to 9.9 g per dose, equivalent to 250 ml of beer or 100 ml of wine.

This medicine is harmful for individuals suffering from alcoholism.

The alcohol content should be considered in pregnant or breastfeeding 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 alcohol content in this medicine may impair your ability to drive or operate machinery.

Gemcitabina Accord contains sodium. Patients on a low-sodium diet 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 metre of your body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this body surface area to calculate the correct dose for you. This dose may be adjusted or the treatment may be delayed depending on your overall health and your blood cell counts.

The frequency with which you receive Gemcitabine Accord infusion depends on the type of cancer for which you are being treated.

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

Gemcitabine Accord will always be given to you as an intravenous infusion into one of your veins. The infusion will last approximately 30 minutes.

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

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

4. Possible adverse effects

Like all medicines, Gemcitabine Accord can cause adverse effects, although not everyone experiences them.

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

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

??Tiredness, feeling faint, becoming easily breathless, or if you are pale (as you may have lower than normal haemoglobin levels, which is very common).

??Mild to moderately severe 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, purpura and small areas of bleeding under the skin (bruising), acute kidney failure (little or no urination), and signs of infection (haemolytic uraemic syndrome). This may be fatal (uncommon).

??Difficulty breathing (it is very common to experience mild difficulty breathing immediately after Gemcitabine Accord infusion, which soon passes; however, more serious lung problems may occur uncommonly or rarely).

??Severe chest pain (myocardial infarction) (rare).

??Severe allergic/hypersensitivity reaction with severe skin rash including itching and redness of the skin, swelling of hands, feet, ankles, face, lips, mouth and throat (which may cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and feeling faint (anaphylactic reaction) (very rare).

??Generalised swelling, difficulty breathing or weight gain, as you may experience leakage of fluid from small blood vessels into tissues (capillary leak syndrome) (very rare).

??Headache with visual disturbances, confusion, seizures or epileptic fits (reversible posterior encephalopathy syndrome) (very rare).

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

• Extreme fatigue and weakness, purpura or small areas of bleeding under the skin (bruising), acute kidney failure (low or no urine output), and signs of infection. These may be features of thrombotic microangiopathy (clot formation in small blood vessels) and haemolytic uraemic syndrome, which may be fatal.

??Generalised red, scaly rash, with inflamed bumps under the skin (including skin folds, trunk and upper limbs), and blisters, accompanied by fever (Acute Generalized Exanthematous Pustulosis [AGEP]) (frequency not known).

Other adverse effects of Gemcitabine Accord may include:

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

• Low white blood cell count

??Difficulty breathing

??Vomiting

??Nausea

??Hair loss

??Liver problems: detected via abnormal blood test results

??Blood in urine

??Abnormal urine tests: protein in urine

??Flu-like syndrome including fever

??Swelling of ankles, fingers, feet, face (oedema)

Common (may affect up to 1 in 10 people)

??Loss of appetite (anorexia)

??Headache

??Insomnia

??Drowsiness

??Cough

??Stuffy nose

??Constipation

??Diarrhoea

??Itching

??Excessive sweating

??Muscle pain

??Back pain

??Fever

??Feeling weak

??Chills

??Infections

Uncommon (may affect up to 1 in 100 people)

??Damage to lung alveoli (Interstitial lung disease)

??Noisy breathing (spasm in the airway)

??Lung damage (abnormal chest X-ray/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, ulceration or blistering of the skin

??Reactions at the injection site

• Formation of large blisters on the skin or skin exudation

??Gangrene of fingers or toes

??Fluid in the lungs

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

??Sunburn-like skin rash, which may occur in skin previously exposed to radiotherapy (radiation-induced skin toxicity)

??Damage to lung alveoli associated with radiotherapy (radiation-associated toxicity)

??Inflammation of blood vessels (peripheral vasculitis)

??Elevated liver values (GGT)

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

??Increased platelet count

??Inflammation of the large intestine membrane due to reduced blood supply (ischaemic colitis)

??Thrombotic microangiopathy: formation of clots in small blood capillaries. Low haemoglobin (anaemia) and low white blood cell and platelet counts will be detected by blood testing.

Frequency not known (cannot be estimated from available data)

??Sepsis: when bacteria and their toxins circulate in the blood and begin to damage organs

??Pseudocellulitis: skin redness with swelling

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

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, hospital pharmacist or nurse, even if they are not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse 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 prior to dilution:

Each vial is for single use only 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 with 0.9% sodium chloride, physicochemical stability has been demonstrated for up to 60 days at 25°C and at 2°C – 8°C.

From a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the in-use storage time and conditions will be the responsibility of the user and normally should not exceed 24 hours at 2°C – 8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

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

6. Contents of the pack and other information

Contents of Gemcitabine Accord

The active substance is gemcitabine. Each ml of concentrate for solution for infusion contains 100 mg of gemcitabine (as gemcitabine hydrochloride). Each vial contains 1500 mg of gemcitabine (as gemcitabine hydrochloride).

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

Nature and contents of the container

Gemcitabine Accord is a clear, colourless or slightly yellow solution.

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

Pack sizes

1 vial of 2 ml.

1 vial of 10 ml.

1 vial of 15 ml.

1 vial of 20 ml.

Only some pack 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, 6th floor

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

Member State	Medicinal Product Name
Netherlands	Gemcitabine Accord 100 mg/ml Concentrate for Solution for Infusion
Austria	Gemcitabin Accord 100 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Belgium	Gemcitabine Accord Healthcare 100 mg/ml Solution à Diluer pour Perfusion / Concentrate for Solution for Infusion / Konzentrat zur Herstellung einer Infusionslösung
Bulgaria	Gemcitabine Accord 100 mg/ml Concentrate for Solution for Infusion
Cyprus	Gemcitabine Accord 100 mg Concentrate for Solution for Infusion
Czech Republic	Gemcitabine Accord 100 mg/ml Koncentrát pro Přípravu Infuzního Roztoku
Germany	Gemcitabine Accord 100 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Denmark	Gemcitabin Accord
Estonia	Gemcitabine Accord 100 mg/ml
Greece	GEMCITABINE / ACCORD
Spain	Gemcitabina Accord 200 mg, 1,000 mg, 1,500 mg and 2,000 mg concentrate for solution for perfusion
Finland	Gemcitabine Accord 100 mg/ml Infuusiokonsentraatti, Liuosta Varten
Hungary	Gemcitabine Accord 100 mg/ml Concentrate for Solution for Infusion
Ireland	Gemcitabine 100 mg/ml Concentrate for Solution for Infusion
Italy	GEMCITABINA ACCORD
Latvia	Gemcitabine Accord 100 mg/ml koncentrats infūzijas šķīduma pagatavošanai
Lithuania	Gemcitabine Accord 100 mg/ml koncentratas infuziniam tirpalui
Malta	Gemcitabine 100 mg/ml Concentrate for Solution for Infusion
Norway	Gemcitabine Accord
Poland	Gemcitabinum Accord
Portugal	Gemcitabine Accord
Slovakia	Gemcitabine 100 mg/ml concentrate for solution for infusion
Romania	Gemcitabina 100 mg/ml concentrate for solution for infusion
Sweden	Gemcitabine Accord

Date of the most recent review of this leaflet: November 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency of 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

Gemcitabina Accord requires appropriate dilution before use. The concentration of gemcitabine in Gemcitabina Accord differs from that in other gemcitabine-containing products.

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

Gemcitabina Accord has a higher concentration (100 mg/ml) than other medicinal products containing gemcitabine for intravenous infusion.

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

• Gemcitabina Accord is a clear, colourless or slightly yellow solution with a concentration of 100 mg/ml of gemcitabine. The total amount of Gemcitabina Accord required for a patient must be diluted with sterile sodium chloride solution 9 mg/ml (0.9%). The solution may then be further diluted with the same diluent to a final concentration of 0.1 to 9 mg/ml. The diluted solution is clear, colourless or slightly yellow.

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

Special storage precautions

After opening and before dilution:

Each vial is for single use only and should be used immediately after opening. If not used immediately, the storage conditions and periods prior to use shall be the responsibility of the user.

After dilution:

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

From a microbiological standpoint, the infusion solution should be used immediately. If not used immediately, the conditions and periods of storage prior to use shall 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

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

• If vials have been stored in the refrigerator, allow Gemcitabina Accord containers to reach below 25°C for 5 minutes before use. More than one vial of Gemcitabina Accord may be required to obtain the patient's required dose.

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

• The required volume of Gemcitabina Accord should be injected into an infusion bag containing 9 mg/ml (0.9%) sodium chloride solution for infusion.

• Mix the infusion bag manually with a rocking motion. The solution may 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 ~2.25 g for gemcitabine, concentrations of 4.5 mg/ml (achieved with 500 ml of diluent) to 9 mg/ml (achieved with 250 ml of diluent) correspond to an osmolarity of approximately 1000 mOsmol/kg to 1700 mOsmol/kg.

• As with all parenteral medicinal products, the gemcitabine infusion solution should be inspected visually prior to administration to detect any particulate matter or discoloration. If particulates are observed, do not administer.

Preparation and administration precautions

Standard safety measures for cytotoxic agents must be observed when preparing and disposing of the infusion solution. The solution should be handled in a safety cabinet and protective clothing and gloves should be worn. If a safety cabinet is not available, protective masks and eye protection should be used in addition.

If the preparation comes into contact with the eyes, it may cause severe irritation. Immediately rinse the eyes thoroughly and continuously with abundant water. If irritation persists, consult a physician. If the solution is spilled onto the skin, wash thoroughly with abundant water.

Disposal

The disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.