Gemcitabine Prasfarma 200 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Gemcitabina Prasfarma 200 mg concentrate for solution for infusion

Gemcitabine

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• 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 adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

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

Gemcitabina Prasfarma is a medicine used to treat cancer and belongs to a group of medicines called "cytotoxic agents". These medicines destroy cells that are dividing, including cancer cells.

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

Gemcitabina Prasfarma 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

2. What you need to know before using Gemcitabine Prasfarma

Do not use Gemcitabine Prasfarma:

• If you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
• If you are breastfeeding, you must interrupt breastfeeding during treatment with Gemcitabine Prasfarma.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Gemcitabine Prasfarma.

Before the first infusion, blood samples will be taken to assess whether your liver and kidney function are normal. Likewise, prior to each infusion, blood samples will be taken to evaluate whether you have enough red blood cells to receive Gemcitabine Prasfarma. 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 or have previously had liver, heart, blood vessel, or kidney disease.
• You have recently undergone or are about to receive radiotherapy, 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 medicine you experience symptoms such as headache with confusion, seizures (attacks), or changes in vision, contact your doctor immediately. This could be a very rare adverse effect affecting the nervous system called reversible posterior encephalopathy syndrome.
• You experience difficulty breathing or feel very weak and pale (this may be a sign of lung problems or kidney failure).
• You suffer from alcoholism, as this medicine contains ethanol (alcohol).
• You have epilepsy, as this medicine contains ethanol (alcohol).
• You experience capillary leak syndrome (CLS), in which fluids from your 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 of blood pressure.
• You have ever developed a severe skin rash, skin peeling, blisters, and/or mouth sores 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 notice any symptoms related to these severe skin reactions described in section 4.

Children and adolescents

The safety and efficacy of gemcitabine in the pediatric population have not been established. No data are available.

Interaction of Gemcitabine Prasfarma with other medicines

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

Pregnancy, breastfeeding, and fertility

Pregnancy

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

Gemcitabine should be avoided during pregnancy. Your doctor will discuss with you the potential risks of taking gemcitabine during pregnancy.

Breastfeeding

Inform your doctor if you are breastfeeding.

You must interrupt breastfeeding during treatment with gemcitabine.

Fertility

Men are advised not to father a child during treatment with gemcitabine and for 6 months after treatment ends. If you wish to father a child during treatment or within 6 months after treatment, consult your doctor or pharmacist. You may wish to seek information about sperm preservation before starting treatment.

Driving and using machines

Gemcitabine Prasfarma may cause drowsiness, especially if you have consumed alcohol. Avoid driving or operating machinery until you are certain that treatment with Gemcitabine Prasfarma does not make you drowsy.

Gemcitabine Prasfarma 200 mg contains 893 mg of alcohol (ethanol) per vial, equivalent to 44.65% (w/v). The amount in the maximum dose of 2,250 mg of this medicine is equivalent to 252 ml of beer or 101 ml of wine.

The alcohol contained in this medicine may affect children. Effects may include behavioral changes and drowsiness. It may also affect your ability to concentrate and perform physical activities. The amount of alcohol in this medicine may affect your ability to drive and operate machinery, as it may impair your judgment and reaction time. If you have epilepsy or liver problems, consult your doctor or pharmacist before taking this medicine.

The amount of alcohol in this medicine may alter the effect of other medicines. Consult your doctor or pharmacist if you are taking other medicines.

If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medicine.

If you are alcohol-dependent, consult your doctor or pharmacist before taking this medicine.

Gemcitabine Prasfarma contains 190.98 mg of sodium (main component of table/cooking salt) in the maximum dose of 2,250 mg. This corresponds to 9.55% of the maximum daily recommended sodium intake for an adult.

Gemcitabine Prasfarma 200 mg contains 300 mg of propylene glycol per vial, equivalent to 150 mg/ml.

If you are pregnant or breastfeeding, do not take this medicine unless recommended by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

If you have hepatic or renal impairment, do not take this medicine unless recommended by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

3. How to use Gemcitabine Prasfarma

The recommended dose is 1,000–1,250 mg per square meter 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 determine the correct dose for you. This dose may be adjusted or the treatment may be delayed depending on your overall health and blood cell counts.

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

A hospital pharmacist or physician will have diluted the Gemcitabine Prasfarma concentrate before administration.

Gemcitabine Prasfarma will always be administered 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, Gemcitabina Prasfarma may cause adverse effects, although not everyone will experience them.

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 (because you may have fewer platelets than normal, which is very common).
• Tiredness, feeling faint, becoming easily short of breath, or looking pale (because you may have less hemoglobin than normal, 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 (because 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) (frequency not known).
• Difficulty breathing (it is very common to experience mild difficulty breathing immediately after infusion of Gemcitabina Prasfarma, which passes quickly; however, more serious lung problems may occur infrequently or rarely).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity / allergic 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 like you might faint (anaphylactic reaction) (very rare).
• Generalized swelling, difficulty breathing, or weight gain, as you may experience fluid leakage from small blood vessels into tissues (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures or 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 tiredness and weakness, purpura or small bleeding areas on the skin (bruises), acute kidney injury (low urine output or absence of urine), and signs of infection. These may be signs of thrombotic microangiopathy (clots forming in small blood vessels) and hemolytic uremic syndrome, which can be fatal.
• Generalized 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 Gemcitabina Prasfarma may include:

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

• Low white blood cell count
• Low platelet count
• Difficulty breathing
• Vomiting
• Nausea
• Hair loss
• Liver problems: detected through abnormal blood test results
• Blood in urine
• Abnormal urine tests: protein in urine
• Pseudoflu-like syndrome including fever
• Edema (swelling of ankles, fingers, feet, face)

Common (may affect up to 1 in 10 people)

• Anorexia (loss of appetite)
• Headache
• Insomnia
• Drowsiness
• Cough
• Nasal congestion
• Constipation
• Diarrhea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Uncommon (may affect up to 1 in 100 people)

• Interstitial pneumonitis (hardening of the walls of the lung alveoli)
• Airway spasm (wheezing)
• Abnormal chest X-ray/scan (hardening of the lung walls)
• Heart failure
• Cerebral infarction (stroke)
• Severe liver damage, including liver failure
• Kidney failure

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

• Low blood pressure
• Skin peeling, ulceration, or blister formation
• Reactions at the injection site
• Gangrene of fingers or toes
• Fluid in the lungs
• Adult respiratory distress syndrome (severe lung inflammation causing respiratory failure)
• Late radiation-induced skin toxicity (a sunburn-like skin rash) that may occur in skin previously exposed to radiotherapy
• Radiation-associated toxicity – hardening of the walls of the lung alveoli associated with radiotherapy
• Inflammation of blood vessels (peripheral vasculitis)
• Skin peeling and development of severe blisters on the skin

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

• Increased platelet count
• Ischemic colitis (inflammation of the lining of the large intestine caused by reduced blood supply)
• Thrombotic microangiopathy: clots forming in small blood vessels

Frequency not known

• Sepsis: when bacteria and their toxins circulate in your blood and begin to damage organs
• Pseudocellulitis: redness of the skin with swelling

Low hemoglobin levels (anemia), low white blood cells, and low platelet count may be detected by blood tests.

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

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

This medicine does not require any special storage conditions.

Vials opened prior to dilution:

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

Diluted solution:

Chemical and physical stability has been demonstrated after dilution in 0.9% sodium chloride solution for 24 hours 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 conditions and duration of storage prior to use shall be the responsibility of the user and must not exceed 24 hours at 2°C – 8°C, unless the dilution is carried out under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date which is 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 personnel.

6. Contents of the pack and other information

Composition of Gemcitabine Prasfarma

The active substance is gemcitabine. Each millilitre contains gemcitabine hydrochloride equivalent to 100 mg of gemcitabine.

Each 2 ml vial contains gemcitabine hydrochloride equivalent to 200 mg of gemcitabine.

The other components (excipients) are macrogol 300, propylene glycol (E-1520), anhydrous ethanol, sodium hydroxide (E-524) (to adjust pH), and concentrated hydrochloric acid (E-507) (to adjust pH).

Appearance of the product and contents of the pack

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

Gemcitabine Prasfarma is packaged in a colourless Type I glass vial sealed with rubber stoppers and secured with an aluminium cap.

Pack sizes

1 vial of 2 ml.

1 vial of 10 ml.

1 vial of 20 ml.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Prasfarma S.L.U.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

This leaflet was approved in: April 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.es/**

The following information is intended exclusively for healthcare professionals:

Instructions for use, handling, and disposal

Gemcitabine Prasfarma requires appropriate dilution before use. The concentration of gemcitabine in Gemcitabine Prasfarma differs from other gemcitabine products.

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

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

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

• Gemcitabine Prasfarma is a clear, colourless to slightly yellow solution with a concentration of 100 mg/ml of gemcitabine. The total amount of Gemcitabine Prasfarma required for a patient must be diluted with sterile sodium chloride 9 mg/ml (0.9%) solution. The final diluted solution concentration prepared using the maximum dose of gemcitabine (~2.25 g) should be approximately 0.2 to 9 mg/ml. To achieve a concentration of 0.2 mg/ml, dilute with 8500 ml of diluent. To achieve a concentration of 4.5 mg/ml, dilute with 500 ml of diluent. To achieve a concentration of 9 mg/ml, dilute with 250 ml of diluent.

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

Vials opened prior to dilution:

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

Diluted solution:

Chemical and physical stability after dilution in 0.9% sodium chloride solution has been demonstrated for 24 hours 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 storage conditions and periods prior to use shall be the responsibility of the user and must not exceed 24 hours at 2°C–8°C, unless dilution is performed under controlled and validated aseptic conditions.

Preparation of the infusion solution

Gemcitabine Prasfarma 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 the Gemcitabine Prasfarma containers to reach below 25°C for 5 minutes before use. More than one vial of Gemcitabine Prasfarma may be required to obtain the dose required for the patient.

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

• The required volume of Gemcitabine Prasfarma must be injected into an infusion bag containing 0.9% sodium chloride 9 mg/ml solution.

• Mix the infusion bag manually with an oscillating motion. The solution may then be further diluted with the same solvent to a final concentration of approximately 0.2 to 9 mg/ml, considering the maximum dose of ~2.25 g for gemcitabine. To achieve a concentration of 0.2 mg/ml, dilute with 8500 ml of diluent. To achieve a concentration of 4.5 mg/ml, dilute with 500 ml of diluent. To achieve a concentration of 9 mg/ml, dilute with 250 ml of diluent.

• As with all parenteral medicines, the gemcitabine infusion solution must be visually inspected prior to administration to detect particulate matter or discoloration. If particles 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 must be handled in a safety cabinet, and protective clothing and gloves must be worn. If a safety cabinet is not available, additional protective equipment including masks and eye protection should be used.

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

Disposal

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