PEMETREXED PRASFARMA 100 mg POWDER FOR CONCENTRATE FOR PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Pemetrexed Prasfarma 100 mg powder for concentrate for solution for infusion EFG

for infusion

pemetrexed

Read all of this leaflet carefully before you start receiving this medicine because it contains important information for you.

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

Contents of the pack

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

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

Pemetrexed Prasfarma is a medicine used to treat cancer.

Pemetrexed Prasfarma can be given with cisplatin, another anticancer medicine, as a treatment for malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received chemotherapy before.

Pemetrexed Prasfarma can also be given, along with cisplatin, as an initial treatment for patients with advanced stages of lung cancer.

Pemetrexed Prasfarma may be prescribed for you if you have advanced lung cancer, if your disease has responded to treatment or if it remains unchanged after initial chemotherapy.

Pemetrexed Prasfarma can also be given for the treatment of those patients in advanced stages of lung cancer whose disease has progressed, who have already received other initial chemotherapy treatment.

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

Do not use Pemetrexed Prasfarma:

• if you are allergic (hypersensitive) to pemetrexed or any of the other ingredients of Pemetrexed Prasfarma (listed in section 6).
• if you are breastfeeding, you must stop breastfeeding during treatment with Pemetrexed Prasfarma.
• if you have recently received or are going to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or pharmacist before you are given Pemetrexed Prasfarma.

If you have had or have kidney problems, tell your doctor or hospital pharmacist, as you may not be able to receive Pemetrexed Prasfarma.

Before each infusion, you will need to give blood samples to check if your kidney and liver function is sufficient and to check if you have enough blood cells to receive Pemetrexed Prasfarma. Your doctor may decide to change your dose or delay treatment depending on your general condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will make sure you are properly hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are going to receive radiotherapy, please consult your doctor, as an early or late reaction may occur between radiation and Pemetrexed Prasfarma.

If you have been vaccinated recently, please consult your doctor, as this may cause some negative effect with Pemetrexed Prasfarma.

If you have a heart condition or a history of heart disease, please consult your doctor.

If you have fluid accumulated around the lung, your doctor may decide to remove the fluid before administering Pemetrexed Prasfarma.

Children and adolescents

No relevant data are available on the use of Pemetrexed Prasfarma in the pediatric population.

Use of Pemetrexed Prasfarma with other medicines

Tell your doctor if you are taking medicines for pain or inflammation (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (NSAIDs), including those purchased without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your Pemetrexed Prasfarma infusion and/or the status of your kidney function, your doctor will advise you which medicines you can use and when you can take them. If you are not sure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

Tell your doctor if you are taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) used to treat stomach acid and acid reflux.

Tell your doctor or hospital pharmacist if you are using or have recently used other medicines, including those purchased without a prescription.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, inform your doctor.

Pemetrexed Prasfarma should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking Pemetrexed Prasfarma during pregnancy. Women must use effective contraceptive methods during treatment with Pemetrexed Prasfarma.

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding should be stopped during treatment with Pemetrexed Prasfarma.

Fertility

Male patients are advised not to father a child during and up to 6 months after treatment with Pemetrexed Prasfarma and must use effective contraceptive methods during and up to 6 months after treatment with Pemetrexed Prasfarma. If you wish to have a child during treatment or in the 6 months following treatment, ask your doctor or pharmacist for advice. You may want to ask for information about sperm preservation before starting your treatment.

Driving and using machines

Pemetrexed Prasfarma may make you feel tired. Be careful when driving a vehicle or using machines.

Pemetrexed Prasfarma contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per vial; it is essentially "sodium-free".

3. How to use Pemetrexed Prasfarma

The dose of Pemetrexed Prasfarma is 500 milligrams 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 surface area to calculate the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell count and your general condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Prasfarma powder with a sodium chloride solution for injection of 9 mg/ml (0.9%) before it is administered to you.

You will always receive Pemetrexed Prasfarma through an infusion (drip) in one of your veins. The infusion will last at least 10 minutes.

When using Pemetrexed Prasfarma in combination with cisplatin:

Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also given through an infusion in one of your veins and is given approximately 30 minutes after the Pemetrexed Prasfarma infusion has finished. The cisplatin infusion lasts approximately two hours.

Normally, you should receive your infusion once every three weeks.

Additional medication:

Corticosteroids: your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will need to take the day before, the day of, and the day after treatment with Pemetrexed Prasfarma. Your doctor gives you this medicine to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.

Vitamin supplement: your doctor will prescribe oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms) that you should take once a day while taking Pemetrexed Prasfarma. You should take at least five doses during the seven days before the first dose of Pemetrexed Prasfarma. You should continue taking folic acid for 21 days after the last dose of Pemetrexed Prasfarma. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before Pemetrexed Prasfarma administration and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Prasfarma). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

You must inform your doctor immediately if you notice any of the following symptoms:

• Fever or infection (frequent): if you have a temperature of 38°C or higher, sweating, or other signs of infection (as you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be severe and life-threatening.
• If you start to feel chest pain (frequent) or your heart rate is faster (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very frequent).
• Allergic reaction: if you develop a rash (very frequent), burning sensation, or itching (frequent), or fever (frequent). In rare cases, skin reactions can be severe and life-threatening. Contact your doctor if you experience severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you are short of breath or pale (due to having fewer red blood cells than normal, which is very frequent).
• If you experience bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (due to having fewer platelets than normal, which is very frequent).
• If you experience sudden difficulty breathing, severe chest pain, or coughing up blood (uncommon) (may indicate a blood clot in the lungs).

Side effects with Pemetrexed Prasfarma can include:

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

• Low white blood cell count
• Low hemoglobin levels (anemia)
• Low platelet count
• Diarrhea
• Vomiting
• Pain, redness, swelling, or sores in the mouth
• Nausea
• Loss of appetite
• Asthenia (fatigue)
• Rash
• Hair loss
• Constipation
• Numbness
• Kidney: changes in blood tests

Common (may affect up to 1 in 10 people)

• Allergic reaction: rash / burning sensation or itching
• Infection, including sepsis
• Fever
• Dehydration
• Kidney failure
• Skin irritation and itching
• Chest pain
• Muscle weakness
• Conjunctivitis (eye inflammation)
• Upset stomach
• Abdominal pain
• Changes in taste
• Liver: changes in blood tests
• Tearing
• Increased skin pigmentation

Uncommon (may affect up to 1 in 100 people)

• Acute kidney failure
• Increased heart rate
• Esophageal mucositis (inflammation of the esophagus) after combination of Pemetrexed Prasfarma and radiotherapy.
• Colitis (inflammation of the colon, which may be accompanied by intestinal or rectal bleeding).
• Interstitial pneumonitis (scarring of the lung tissue).
• Edema (excess fluid in the body tissues that causes swelling).
• Some patients have experienced a heart attack, embolism, or "mini-stroke" while receiving Pemetrexed Prasfarma, usually in combination with other anticancer treatment.
• Pancytopenia: combination of low white blood cell count, low red blood cell count, and low platelet count.
• Radiation pneumonitis (scarring of the lung air sacs associated with radiotherapy) may occur in patients being treated with radiation before, during, or after treatment with Pemetrexed Prasfarma.
• Arm or leg pain, low temperature, and changes in skin color have been reported.
• Blood clots in the lungs (pulmonary embolism).

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

• Delayed skin toxicity (skin rash similar to severe sunburn) that can appear on skin that has been previously exposed to radiation, from days to years after radiation.
• Bullous disorders (diseases with blistering of the skin) including Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Immune-mediated hemolytic anemia (destruction of red blood cells by antibodies).
• Hepatitis (inflammation of the liver).
• Anaphylactic shock (severe allergic reaction).

Frequency not known: frequency cannot be estimated from the available data

Swelling of the lower limbs with pain and redness.

Increased urine output.

Thirst and increased water intake.

Hypernatremia: high sodium levels in the blood.

Skin inflammation, mainly of the lower limbs with swelling, pain, and redness.

You may experience some of these symptoms and/or situations. You should inform your doctor as soon as you start experiencing any of these side effects.

If you are concerned about any side effect, talk to your doctor.

Reporting of side effects

If you experience any side effect, talk to your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pemetrexed Prasfarma

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

Do not use this medicine after the expiry date which is stated on the carton and on the vial label after EXP.

This medicine does not require any special storage conditions.

Reconstituted and infusion solution: the medicine should be used immediately. When prepared as indicated, the chemical and physical stability of the reconstituted and infusion solution is 24 hours in refrigeration.

This medicine is for single use only. The unused solution should be discarded in accordance with local requirements for cytotoxic agents.

This medicine should not be used if the solution contains particles.

This medicine is for single use only.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Pemetrexed Prasfarma

The active ingredient is pemetrexed.

Pemetrexed Prasfarma 100 mg: Each vial contains 100 mg of pemetrexed (as pemetrexed disodium hemipentahydrate).

After reconstitution, the solution contains 25 mg/ml of pemetrexed. Prior to administration, it is required that the healthcare professional perform further dilution.

The other components are mannitol (E-421).

Appearance of the Product and Container Contents

Pemetrexed Prasfarma is a powder for concentrate for solution for infusion in a glass vial. It is a lyophilized powder of white to pale yellow or yellowish-green color.

Each package of Pemetrexed Prasfarma contains one vial.

Only certain package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

PRASFARMA S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

Manufacturer

PRASFARMA S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

Date of Last Revision of this Prospectus: January 2025

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.gob.es/)

This information is intended only for healthcare professionals:

Instructions for Use, Handling, and Disposal

1. Use aseptic techniques during the reconstitution and subsequent dilution of pemetrexed for administration via intravenous infusion.

1. Calculate the dose and the number of Pemetrexed Prasfarma vials needed. Each vial contains an excess of pemetrexed to facilitate the administration of the required nominal amount.

1. Reconstitute each 100 mg vial with 4.2 ml of a 0.9% sodium chloride injection solution (9 mg/ml) without preservatives to obtain a solution containing 25 mg/ml of pemetrexed.

Shake the vial carefully until the powder is completely dissolved. The resulting solution is transparent with a color range that may vary from colorless to yellow or yellowish-green without negatively affecting the product quality. The pH of the reconstituted solution is between 6.7 and 7.8. Further dilution is required.

1. The appropriate volume of the reconstituted pemetrexed solution should be diluted to 100 ml with a 0.9% sodium chloride injection solution (9 mg/ml) without preservatives and administered as an intravenous infusion over 10 minutes.

1. The prepared pemetrexed infusion solution, as described above, is compatible with polyvinyl chloride and polyolefin infusion systems and bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer's injection and Ringer's injection.

1. Parenteral medications should be visually inspected prior to administration to rule out the presence of particles or color alteration. If particles are observed, the medication should not be administered.

1. Pemetrexed solutions are for single use. The medication and unused material should be discarded according to local requirements for cytotoxic agents.

Precautions in Preparation and Administration:As with any other potentially toxic antineoplastic agent, special care should be taken in the handling and preparation of pemetrexed infusion solutions. The use of gloves is recommended for handling. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be rinsed with plenty of water.

Pemetrexed is not a vesicant drug. There is no specific antidote for pemetrexed extravasation. Some cases of pemetrexed extravasation have been reported, which were not considered serious by the investigator. Extravasation should be treated according to standard clinical practice with other non-vesicant drugs.