PATIENT INFORMATION LEAFLET

Gemcitabina Prasfarma 1000 mg concentrate for infusion solution

Gemcitabina

Read this 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, consult your doctor, pharmacist or nurse.

- If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before using Gemcitabina Prasfarma

3. How to use Gemcitabina Prasfarma

4. Possible side effects

5. Storage of Gemcitabina Prasfarma

6. Contents of the pack and additional information

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

Gemcitabina Prasfarma is used in the treatment of the following types of cancer:

• lung cancer, of the type “non-small cell” (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 Prasfarma:

- 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 should interrupt breastfeeding during treatment with Gemcitabina Prasfarma.

Warnings and Precautions

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

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 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 evaluate the function of your kidney and liver.

Inform your doctor if:

• You have or have had liver, heart, blood vessel, 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 gemcitabina.
• You have recently been vaccinated, as this could cause negative effects with gemcitabina.
• 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.
• You have ever developed severe skin rash or skin peeling, blisters, and/or mouth sores after using gemcitabina.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized pustular psoriasis (AGPP), have been reported in association with gemcitabina 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

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

Interaction of Gemcitabina Prasfarma 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

Pregnancy

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

The use of gemcitabina should be avoided during pregnancy. Your doctor will discuss the potential risk of taking gemcitabina during pregnancy with you.

Breastfeeding

Inform your doctor if you are breastfeeding.

You should interrupt breastfeeding during treatment with gemcitabina.

Fertility

Men are advised not to decide to have a child during treatment with gemcitabina or within 6 months after treatment. If you wish to have a child during treatment or within 6 months after treatment, consult your doctor or pharmacist. You may wish to request information on sperm conservation before starting your treatment.

Driving and Operating Machines

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

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

The alcohol contained in this medication may affect children. The effects that may appear are changes in behavior and drowsiness. It may also affect your ability to concentrate and perform physical activities. The amount of alcohol contained in this medication may affect your ability to drive and operate machines due to the fact that it may alter your judgment and reaction time. If you suffer from epilepsy or liver problems, consult your doctor or pharmacist before taking this medication.

The amount of alcohol contained in this medication may alter the effect of other medications. Consult with your doctor or pharmacist if you are taking other medications.

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

If you have a history of alcohol addiction, consult with your doctor or pharmacist before taking this medication.

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

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

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

If you have liver or kidney insufficiency, do not take this medication unless recommended by your doctor. Your doctor may perform additional checks while you are taking this medication.

The recommended dose is 1,000-1,250 mg per square meter of your body surface area. Your height and weight are measured to calculate your body area. 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 overall health status and blood cell counts.

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

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

You will always receive Gemcitabina Prasfarma 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 medications, Gemcitabina Prasfarma may cause side effects, although not everyone will experience them.

Contact your doctor immediately if you notice any of the following:

• Bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, unexpected bruises (since you may have fewer platelets than normal, which is very common).
• Fatigue, feeling of dizziness, easily getting winded, or if you are pale (since you may have lower than normal hemoglobin, 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 (since 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 heart rate (arrhythmia) (frequency unknown).
• Difficulty breathing (it is very common to have mild difficulty breathing immediately after the infusion of Gemcitabina Prasfarma, which passes soon, however, infrequently 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 swelling, difficulty breathing, or weight gain, as you may suffer from fluid extravasation from small blood vessels to tissues (capillary extravasation syndrome) (very rare).
• Headache with changes in vision, confusion, seizures, or attacks (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 (petechiae), acute kidney injury (low urine output or absence of urine), and signs of infection. These may be signs of microangiopathic thrombosis (clots that form in small blood vessels) and hemolytic uremic syndrome, which can be fatal.
• Generalized red and scaly rash with inflamed skin lumps under the skin (including skin folds, trunk, and upper limbs) and blisters accompanied by fever (Acute Generalized Pustular Exanthema (PEG)) (frequency unknown).

Other side 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: identified through abnormal blood test results
• Blood in the urine
• Abnormal urine test results: protein in the urine
• Symptoms of a flu-like illness, 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

Rare (may affect up to 1 in 100 people)

• Interstitial pneumonitis (hardening of the walls of the lung alveoli)
• Respiratory tract spasm (wheezing)
• Abnormal chest X-ray / CT 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 blistering
• Reactions at the injection site
• Gangrene of the fingers or toes
• Liquid in the lungs
• Adult respiratory distress syndrome (severe lung inflammation that causes respiratory failure).
• Delayed cutaneous toxicity associated with radiation therapy - (severe sunburn-like rash) that may occur in skin previously exposed to radiation therapy.
• Radiation therapy-associated toxicity - hardening of the lung alveoli walls associated with radiation therapy.
• Peripheral vasculitis (inflammation of blood vessels).
• Severe skin peeling and blistering.

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

• Increased platelet count
• Ischemic colitis (inflammation of the intestinal membrane, caused by reduced blood supply)
• Microangiopathic thrombosis: clots that form in small blood vessels.

Frequency unknown

• Sepsis: when bacteria and their toxins circulate in your blood and start damaging organs.
• Pseudocellulitis: skin redness with swelling.

These may be detected through blood tests, low hemoglobin levels (anemia), low white blood cell count, and platelet count.

You may have any of these symptoms and/or conditions. 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 are not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

This medication does not require special storage conditions.

Pre-dilution vials:

Each single-use vial must be used immediately after opening. If not used immediately, storage conditions and periods prior to 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 at 2°C – 8°C.

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

Composition of Gemcitabina Prasfarma

The active ingredient is gemcitabina.Each milliliter contains hydrochloride equivalent to 100 mg of gemcitabina.

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

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

Aspect of the product and packaging content

Gemcitabina Prasfarma is a transparent, colorless or slightly yellowish solution.

Gemcitabina Prasfarma is packaged in a colorless Type I glass vial sealed with rubber stoppers and sealed with an aluminum capsule.

Packaging sizes

1 vial of 2 ml.

1 vial of 10 ml.

1 vial of 20 ml.

Only some packaging sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Prasfarma S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

This leaflet has been approved in: April 2024

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.es/
The following information is only directed to healthcare professionals:

Instructions for use, handling and disposal

Gemcitabina Prasfarma requires an appropriate dilution before use. The concentration of gemcitabina in Gemcitabina Prasfarma differs from other products with gemcitabina.

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

Gemcitabina Prasfarma contains a higher concentration (100 mg/ml) than other gemcitabina-containing medications for intravenous infusion.

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

• Gemcitabina Prasfarma is a transparent, colorless to slightly yellowish solution with a concentration of 100 mg/ml of gemcitabina. The total amount of Gemcitabina 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 gemcitabina dose (~ 2.25g) should 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 transparent, colorless or slightly yellowish.

• Storage of the diluted gemcitabine solution in PVC containers may produce DEHP (di-(2-ethylhexyl)phthalate) leaching, consequently, the preparation, storage and administration of the diluted solution should be carried out 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 storage conditions and periods 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 storage conditions and periods 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 in controlled and validated aseptic conditions.

Preparation of the infusion solution

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

• If the vials are stored in the refrigerator, let the Gemcitabina Prasfarma containers be below 25°C for 5 minutes before use. It may be necessary to use more than one vial of Gemcitabina Prasfarma to obtain the required dose for the patient.

• Using a calibrated syringe, remove the required amount of Gemcitabina Prasfarma aseptically.

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

• Mix the infusion bag manually with an oscillating motion. It can then be 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 gemcitabina. 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 should be taken into account when preparing and disposing of the infusion solution. The manipulation of the solution should be carried out in a safety cabinet and protective clothing and gloves should be used. 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 thoroughly rinsed with plenty of water immediately. If the irritation persists, a doctor should be consulted. If the solution is spilled on the skin, it should be thoroughly rinsed with plenty of water.

Disposal

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