GEMCITABINE PRASFARMA 200 MG CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Gemcitabine Prasfarma

Do not use Gemcitabine Prasfarma:

• 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 Prasfarma.

Warnings and precautions

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

Before the first infusion, blood samples will be taken to check if your liver and kidney function is correct. Also, before each infusion, blood samples will be taken to check if you have enough red blood cells to receive Gemcitabine Prasfarma. 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 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 recently been vaccinated, as this could 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 adverse effect of the nervous system called posterior reversible encephalopathy syndrome.
• you have difficulty breathing or feel very weak and very pale (it 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 your 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.
• you have developed a severe skin rash or skin peeling, blisters, and/or sores in the mouth 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 medical attention immediately if you notice any of the 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

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

Pregnancy

If you are pregnant or think you may be pregnant or 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 risk of taking gemcitabine during pregnancy.

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 up to 6 months after treatment. If you wish to father a child during treatment or in the 6 months after treatment, consult your doctor or pharmacist. You may want to ask for information on sperm conservation before starting treatment.

Driving and using machines

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

Gemcitabine Prasfarma 200 mg contains 893 mg of alcohol (ethanol)in each vial, which is equivalent to 44.65% (v/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 in this medicine may affect children. The effects that may appear are changes in behavior and drowsiness. It may also affect their ability to concentrate and perform physical activities. The amount of alcohol in this medicine may affect your ability to drive and use machines because it may alter your judgment and reaction ability. 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 breast-feeding, consult your doctor or pharmacist before taking this medicine.

If you have a history of alcoholism, consult your doctor or pharmacist before taking this medicine.

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

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

If you are pregnant or breast-feeding, do not take this medicine unless your doctor recommends it. Your doctor may perform additional checks while you are taking this medicine.

If you have liver or kidney failure, do not take this medicine unless your doctor recommends it. Your doctor may perform additional checks 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 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 Prasfarma infusion depends on the type of cancer you are being treated for.

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

You will always receive Gemcitabine Prasfarma 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 Prasfarma can cause side effects, although not everybody gets 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 (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 fewer red blood cells 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 (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) (frequency not known).
• Difficulty breathing (it is very common to have mild difficulty breathing immediately after the infusion of Gemcitabine Prasfarma, which passes soon, 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 of the skin, 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 suffer from fluid leakage 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 rash with itching, blisters, or skin peeling (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Extreme tiredness and weakness, purpura, or small bleeding spots on the skin (petechiae), acute kidney injury (low urine output or absence of urine), and signs of infection. These may 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 of Gemcitabine 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: identified through abnormal blood test results
• Blood in the urine
• Abnormal urine tests: protein in the urine
• Pseudo-flu 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
• Stuffy nose
• Constipation
• Diarrhea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Uncommon (may affect up to 1 in 100 people)

• Interstitial pneumonitis (scarring of the lung tissue)
• Spasm of the airways (wheezing)
• Abnormal chest X-ray/scanner (scarring of the lung tissue)
• Heart failure
• Stroke
• 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
• Reactions at the injection site
• Gangrene of the fingers or toes
• Fluid in the lungs
• Adult respiratory distress syndrome (severe lung inflammation that causes respiratory failure).
• Late radiation toxicity associated with radiotherapy - a skin rash similar to severe sunburn that can occur in skin that has been previously exposed to radiotherapy.
• Radiation toxicity - scarring of the lung tissue associated with radiotherapy.
• Inflammation of the blood vessels (peripheral vasculitis).
• Peeling of the skin and 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: blood clots forming in small blood vessels.

Frequency not known

• Sepsis: when bacteria and their toxins circulate in your blood and start to damage your organs.
• Pseudo-cellulitis: redness of the skin with swelling.

Low hemoglobin levels (anemia), low white blood cell count, and low platelet count can be detected through 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 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 Medicines Agency through the website: www.notificaRAM.es. By reporting side 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 before dilution:

Each single-dose vial should be used immediately after opening. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

Diluted solution:

Chemical and physical stability after dilution in sodium chloride 0.9% solution has been demonstrated for 24 hours 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 in-use storage times and conditions are the responsibility of the user and should not exceed 24 hours at 2°C - 8°C, unless the dilution is performed under 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 is the last day of the month stated.

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

6. Container Contents and Additional Information

Composition of Gemcitabine Prasfarma

The active ingredient is gemcitabine. Each milliliter 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) (for pH adjustment), and concentrated hydrochloric acid (E-507) (for pH adjustment).

Appearance of the Product and Container Contents

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

Gemcitabine Prasfarma is packaged in a Type I colorless glass vial sealed with rubber stoppers and capped with an aluminum cap.

Container Sizes

1 vial of 2 ml.

1 vial of 10 ml.

1 vial of 20 ml.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Prasfarma S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

This leaflet was approved in: April 2024

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/The following information is intended only for healthcare professionals:

Instructions for Use, Handling, and Disposal

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

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

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

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

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

The diluted solution is clear, colorless or slightly yellowish.

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

Special Storage Precautions

Opened vials 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.

Diluted solution:

Chemical and physical stability has been demonstrated after dilution in 0.9% sodium chloride solution for 24 hours at 25°C and 2°C – 8°C.

From a microbiological point of view, the solution for infusion 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 Solution for Infusion

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

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

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

• Mix the infusion bag manually with an oscillating movement. Then, it can be further diluted with the same solvent to a final concentration of approximately 0.2 to 9 mg/ml, considering the maximum dose of ~ 2.25g for gemcitabine. To obtain a concentration of 0.2 mg/ml, it must be diluted with 8500 ml of diluent. To obtain a concentration of 4.5 mg/ml, it must be diluted with 500 ml of diluent. To obtain a concentration of 9 mg/ml, it must be diluted with 250 ml of diluent.

• As with all parenteral medications, the gemcitabine infusion solution must 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 must be taken into account when preparing and disposing of the infusion solution. Handling of the solution must be performed in a safety cabinet, and protective suits 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 can cause severe irritation. The eyes must 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 unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.