Label: information for the user

Pemetrexed Prasfarma 100 mg powder for concentrate for solution

for EFG perfusion

pemetrexed

Read this label carefully before starting to receive this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

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

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

3. How to use Pemetrexed Prasfarma

4. Possible adverse effects

5. Storage of Pemetrexed Prasfarma

6. Contents of the package and additional information

Pemetrexed Prasfarma is a medication used for the treatment of cancer.

Pemetrexed Prasfarma can be administered with cisplatino, another anticancer medication, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lung mucosa, in patients who have not received prior chemotherapy.

Pemetrexed Prasfarma can also be administered, along with cisplatino, for the initial treatment of patients in advanced stages of lung cancer.

Pemetrexed Prasfarma may be prescribed 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 administered for the treatment of patients in advanced stages of lung cancer whose disease has progressed, who have already received initial chemotherapy treatment.

No use Pemetrexed Prasfarma:

• if you are allergic (hypersensitive) to pemetrexed or to any of the other components of Pemetrexed Prasfarma (listed in section 6).
• if you are breastfeeding, you should stop breastfeeding during treatment with Pemetrexed Prasfarma.
• if you have recently been given or are to be given the yellow fever vaccine.

Warnings and precautions

Consult your doctor or pharmacist before Pemetrexed Prasfarma is administered.

If you have or have had kidney problems, tell your doctor or hospital pharmacist as it may be possible that you cannot receive Pemetrexed Prasfarma.

Before each infusion, you will need to give blood samples to evaluate if your renal and hepatic function is sufficient and to evaluate 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 ensure that you are properly hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are to receive radiation therapy, please consult with your doctor, as there may be an early or late reaction between the radiation and Pemetrexed Prasfarma.

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

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

If you have fluid accumulated around the lung, your doctor may decide to drain 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

Inform your doctor if you are using pain or anti-inflammatory medicines (such as non-steroidal anti-inflammatory drugs, or NSAIDs), including those purchased over the counter (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 your renal function, your doctor will advise you which medicines you can use and when. If you are unsure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

Inform 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.

Inform your doctor or hospital pharmacist if you are using or have recently used other medicines, including those purchased over the counter.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant or could be 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 should use effective contraceptive methods during treatment with Pemetrexed Prasfarma.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with Pemetrexed Prasfarma, breastfeeding should be interrupted.

Fertility

Men are advised not to father a child during and up to 6 months after treatment with Pemetrexed Prasfarma, and therefore should 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, please consult your doctor or pharmacist. You may wish to request information on sperm preservation before starting your treatment.

Driving and operating machinery

Pemetrexed Prasfarma may make you feel tired. Be careful when driving a vehicle or operating machinery.

Pemetrexed Prasfarma contains sodium

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

The dose of Pemetrexed Prasfarma is 500 milligrams per square meter of the surface area of your body. They will measure your height and weight 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 overall 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 the hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also administered through an infusion in one of your veins and is given approximately 30 minutes after you have finished the Pemetrexed Prasfarma infusion. The cisplatin infusion lasts approximately two hours.

You should normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe some tablets of steroids (equivalent to 4 milligrams of dexamethasone twice a day) that you will have to take the day before, on the same day, and the day after treatment with Pemetrexed Prasfarma. Your doctor gives you this medication to reduce the frequency and severity of skin reactions that 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 must take once a day while taking Pemetrexed Prasfarma. You must take at least five doses during the seven days before the first dose of Pemetrexed Prasfarma. You must continue taking folic acid for 21 days after the last dose of Pemetrexed Prasfarma. You will also receive an injection of vitamin B12 (1,000 micrograms) the week before administration of Pemetrexed Prasfarma and approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Prasfarma). Vitamin B12 and folic acid are given to reduce possible toxic effects of cancer treatment.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience 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 (since you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and cause death.
• If you start to feel chest pain (frequent) or the heart rate is faster (rare).
• If you have mouth pain, redness, swelling, or sores (very frequent).
• Allergic reaction: if you develop hives (very frequent), burning or itching sensation (frequent), or fever (frequent). In rare cases, skin reactions can be severe and may cause death. Contact your doctor if you present severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you lack breath or are pale (because you have fewer hemoglobin than normal, which is very frequent).
• If you experience bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruises (because you have fewer platelets than normal, which is very frequent).
• If you experience sudden difficulty breathing, intense chest pain, or coughing up blood in sputum (rare) (may indicate that there is a blood clot in the veins of the lungs).

The side effects of Pemetrexed Prasfarma may include:

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

• Low white blood cell count
• Low hemoglobin levels (anemia)
• Low platelet count
• Diarrhea
• Vomiting
• Mouth pain, redness, swelling, or sores
• Nausea
• Loss of appetite
• Weakness (asthenia)
• Skin rash
• Hair loss
• Constipation
• Loss of sensation
• Kidney: alterations in blood tests

Frequent (may affect up to 1 in 10 people)

• Allergic reaction: hives / burning or itching sensation
• Infection including sepsis
• Fever
• Dehydration
• Renal failure
• Skin irritation and itching
• Chest pain
• Muscle weakness
• Conjunctivitis (eye inflammation)
• Upset stomach
• Abdominal pain
• Changes in taste
• Liver: alterations in blood tests
• Runny eyes
• Skin darkening

Rare (may affect up to 1 in 100 people)

• Acute renal failure
• Aceeleration of heart rate
• Inflammation of the esophageal mucosa (throat) after combination of Pemetrexed Prasfarma and radiation therapy.
• Colitis (inflammation of the intestinal mucosa, which may be accompanied by intestinal or rectal bleeding).
• Interstitial pneumonitis (hardening of the lung alveoli walls).
• Edema (excess fluid in the body tissues causing swelling).
• Some patients have experienced a heart attack, embolism, or "small embolism" while receiving Pemetrexed Prasfarma, usually in combination with another anticancer treatment.
• Pancitopenia: combination of low white blood cell, red blood cell, and platelet counts
• Radiotherapy-induced pneumonitis (scar formation in the lung air sacs associated with radiation therapy) may occur in patients being treated with radiation either before, during, or after their treatment with Pemetrexed Prasfarma
• Patients have reported pain in the extremities, low temperature, and changes in skin color.
• Blood clots in the lungs (pulmonary embolism).

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

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

Unknown frequency: the frequency cannot be estimated from available data

Swelling of the lower extremities with pain and redness.

Increased urine excretion.

Thirst and increased water consumption.

Hypernatremia: elevated sodium levels in the blood.

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

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

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

Reporting of side effects

If you experience any side effect, consult your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://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.

Do not use this medication after the expiration date that appears on the box and on the vial label after CAD.

This medication does not require special conservation conditions.

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

This medication is for single use. The unused solution must be disposed of in accordance with local requirements for cytotoxic agents.

This medication should not be used if the solution shows any type of particles.

This medication is for single use.

Unused medications should not be thrown into the drains or trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Pemetrexed Composition by 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. Before administration, the healthcare professional must perform another dilution.

The other components are mannitol (E-421).

Appearance of the product and contents of the package

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

Each package of Pemetrexed Prasfarma contains a vial.

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

PRASFARMA S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

Responsible manufacturer

PRASFARMA S.L.

C/ Sant Joan 11-15

08560 Manlleu (Barcelona)

Spain

Last review date of this leaflet: January 2025

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

This information is intended solely 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 number of vials of Pemetrexed Prasfarma required. Each vial contains an excess of pemetrexed to facilitate the administration of the nominal required amount.

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

Shake the vial thoroughly until the powder is completely dissolved. The resulting solution is transparent with a color range that may vary from colorless to yellow or yellow-green without affecting the quality of the product. 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 must be diluted to 100 ml with a sodium chloride 0.9% injection solution (9 mg/ml) without preservatives and must be administered as an intravenous infusion over 10 minutes.

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

1. Parenteral medications must be visually inspected before administration to discard the appearance 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 must be disposed of according to local requirements for cytotoxic agents.

Precautions in preparation and administration:As with any other potentially toxic antineoplastic agent, special care must be taken in the handling and preparation of pemetrexed infusion solutions. The use of gloves for handling is recommended. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and abundantly with water and soap. If pemetrexed solutions come into contact with mucous membranes, wash with abundant water.

Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. 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 non-vesicant drugs.