Package Leaflet: Information for the User

Gemcitabina Accord 1.000 mg concentrate for solution for infusion

Read this 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 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.

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

2. What you need to know before you start using Gemcitabina Accord

3. How to use Gemcitabina Accord

4. Possible side effects

5. Storage of Gemcitabina Accord

6. Contents of the pack and additional information

Gemcitabina Accord is a medication used to treat cancer that belongs to the group of medications called “cytotoxics”. These medications destroy cells that are dividing, including cancerous cells.

Gemcitabina Accord may be administered alone or in combination with other anticancer medications, depending on the type of cancer.

Gemcitabina Accord is used in the treatment of 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

No use Gemcitabina Accord:

- If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).

- If you are breastfeeding, you must interrupt breastfeeding during treatment with Gemcitabina Accord.

Warnings and precautions

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

Before the first infusion, blood samples will be taken to evaluate if your liver and kidney function is correct. Similarly, before each infusion, blood samples will be taken to evaluate if you have enough red blood cells to receive Gemcitabina 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 evaluate the function of your kidneys and liver.

Inform your doctor if:

• You have ever developed a severe skin rash or skin peeling, blisters, and/or mouth sores after using gemcitabine.
• You have or have had liver, heart, vascular disease, or kidney problems.
• You have recently had, or are about to receive radiation therapy, as there may be an early or late radiation reaction with gemcitabine.
• You have recently been vaccinated, as this could cause adverse effects with gemcitabine.
• During treatment with this medication, you experience symptoms such as headache with confusion, seizures, or changes in vision, call your doctor immediately. This could be a rare and serious side effect of the nervous system called 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 have alcoholism, as this medication contains ethanol (alcohol).
• You have epilepsy, as this medication contains ethanol (alcohol).
• You experience capillary filtration syndrome (CFS), when fluids from your small blood vessels filter into your tissues. Symptoms may include swelling of your legs, face, and arms, weight gain, hypoalbuminemia (low levels of protein in the blood), severe hypotension (low blood pressure), acute kidney failure, and pulmonary edema (fluid-filled lungs).
• You experience reversible posterior encephalopathy syndrome (RPES). Symptoms include decreased level of consciousness, seizures, headache, visual abnormalities, focal neurological signs, and acute elevation of blood pressure.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized pustular psoriasis (AGPP), have been reported in association with gemcitabine treatment. Seek medical attention immediately if you observe any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents

This medication is not recommended for children under 18 years of age due to the lack of safety and efficacy data.

Interaction of Gemcitabina Accord with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including vaccines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy should be avoided. Your doctor will discuss the potential risk of taking Gemcitabina Accord during pregnancy. Women of childbearing potential should use an effective contraceptive method during treatment with Gemcitabina Accord and for 6 months after the last administration.

You must interrupt breastfeeding during treatment with Gemcitabina Accord.

Fertility

Men are advised not to father a child during treatment with Gemcitabina Accord or within 3 months after treatment. Consequently, they should use an effective contraceptive method during treatment with Gemcitabina Accord and for 3 months after treatment. If you wish to father a child during treatment or within 3 months after treatment, consult your doctor or pharmacist. You may wish to request information on sperm preservation before starting your treatment.

Driving and operating machinery

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

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

This medication is harmful to people with alcoholism.

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

The amount of alcohol in this medication may alter the effects of other medications.

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

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

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

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

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

You will always receive Gemcitabina Accord through an infusion into one of your veins. The infusion will last approximately 30 minutes.

This medication is not recommended for children under 18 years old.

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

Like all medicines, Gemcitabina Accord can cause side effects, although not everyone will experience them.

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

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

??Fatigue, feeling faint, easily getting short of breath, or if you are pale (since you may have lower than normal hemoglobin levels, which is very common).

??Mild or 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 (since you may have a lower than normal white blood cell count, accompanied by fever, also known as neutropenia febrile, which is common).

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

??Irregular heart rate (arrhythmia) (rare).

??Extreme fatigue and weakness, purple spots or small areas of bleeding on the skin (bruises), acute kidney failure (little or no urination), and signs of infection. (urémic syndrome). This can be fatal (rare).

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

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

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

??Generalized edema, difficulty breathing, or weight gain, as you may suffer from fluid extravasation from small blood vessels to tissues (capillary leak syndrome) (very rare).

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

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

• Extreme fatigue and weakness, purple spots or small areas of bleeding on the skin (bruises), acute kidney failure (little or no urination), and signs of infection. May be features of microangiopathic hemolytic anemia and urémic syndrome, which can be fatal.

??Generalized red and scaly skin rash, with inflamed skin lumps under the skin (including skin folds, trunk, and upper limbs) and blisters, accompanied by fever (Acute Generalized Pustular Psoriasis [AGPP]) (frequency not known).

Other side effects of Gemcitabina 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: identified through abnormal blood test results

??Blood in the urine

??Abnormal urine test results: protein in the urine

??Flu-like syndrome including fever

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

Common (may affect up to 1 in 10 people)

??Poor appetite (anorexia)

??Headache

??Insomnia

??Drowsiness

??Cough

??Stuffy nose

??Constipation

??Diarrhea

??Itching

??Excessive sweating

??Muscle pain

??Back pain

??Fever

??Feeling weak

??Chills

??Infections

Rare (may affect up to 1 in 100 people)

??Pulmonary alveolar damage(Interstitial lung disease)

??Respiratory wheezing (spasm in the respiratory tract)

??Lung damage (abnormal chest X-ray/CT scan)

??Heart failure

??Liver damage, including liver failure

??Kidney failure

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

??Increased platelet count

??Intestinal membrane inflammation, caused by a reduced blood supply (ischemic colitis).

??Microangiopathic hemolytic anemia: formation of clots in small blood vessels. Low hemoglobin levels (anemia) and low white blood cell and platelet counts will be detected through blood tests.

Frequency not known(cannot be estimated from available data)

??Sepsis: when a bacterium and its toxins circulate in the blood and start to damage organs

??Pseudocellulitis: skin redness with swelling.

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

Reporting side effects

If you experience side effects, consult your doctor, hospital pharmacist, or nurse, even if they do not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

This medication does not require special conditions for conservation.

After opening and before dilution:

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

After dilution:

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

From a microbiological point of view, the infusion solution must be used immediately. If not used immediately, storage time and conditions in use will be the responsibility of the user and are normally not longer than 24 hours at 2°C – 8°C unless the dilution took place in controlled and validated aseptic conditions.

Do not use this medication after the expiration date appearing on the packaging after CAD. The expiration date is the last day of the month indicated.

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

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

Content of Gemcitabine Accord

The active substance is gemcitabine. Each milliliter 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).

Appearance of the product and contents of the pack

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

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

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 responsible

Marketing authorization holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Manufacturer responsible

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 with the following names

Last review date of this leaflet: November 2024

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

The following information is only for healthcare professionals:

Instructions for use, handling and disposal

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

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

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

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

- Gemcitabine Accord is a transparent, 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%). After that, it can be diluted with the same solvent to a final concentration of approximately 0.1 to 9 mg/ml. The diluted solution is transparent, colorless or slightly yellowish.

- The storage of the diluted gemcitabine solution in PVC containers may produce leaching of DEHP (di-(2-ethylhexyl)phthalate), consequently, the 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 and must be used immediately after opening. If not used immediately, the storage conditions and periods before use will be the responsibility of the user.

After dilution:

Chemical and physical stability has been demonstrated for use 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 must be used immediately. If not used immediately, the storage conditions and periods before use will be the responsibility of the user and must not exceed 24 hours at 2°C - 8°C, unless the dilution is carried out in 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 be below 25°C for 5 minutes before use. It may be necessary to use more than one vial of Gemcitabine Accord to obtain the required dose for the patient.

- With a calibrated syringe, remove the required amount of Gemcitabine Accord aseptically.

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

- Mix the infusion bag manually with an oscillating movement. After that, it can be diluted with the same solvent 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 solvent) to 9 mg/ml (achieved with 250 ml of solvent) corresponds to an osmolarity of approximately 1000 mOsmol/Kg to 1700 mOsmol/Kg.

- As with all parenteral medications, the gemcitabine infusion solution must be visually inspected before administration to avoid problems with particles or discoloration. If particles are observed, do not administer.

Precautions for preparation and administration

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

If the preparation comes into contact with the eyes, it may cause severe irritation. The eyes must be flushed immediately with plenty of water. If the irritation persists, a doctor must be consulted. If the solution is spilled on the skin, it must be flushed thoroughly with plenty of water.

Disposal

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