Leaflet:information for theuser

Pemetrexed Ever Pharma 25 mg/ml concentrate for infusion solution

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.
• 1. If you have any questions, consult yourdoctor,pharmacistor nurse.
• If you experience any side effects,consult your doctor,pharmacistor nurse,even if they are not listed in this leaflet. See section 4.

1.What Pemetrexed Ever Pharma is and what it is used for

2.What you need to knowbeforestarting touse Pemetrexed Ever Pharma

3.How to use Pemetrexed Ever Pharma

4.Possible side effects

5Storage of Pemetrexed Ever Pharma

6. Contents of the pack and additional information

This medication is used for the treatment of cancer. It contains the active ingredient pemetrexed. Pemetrexed belongs to a group of medications known as folic acid analogs and interrupts the processes that are essential for cell division.

This medicationmay be administered in combination with cisplatin, 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.

This medicationmay also be administered, in combination with cisplatin, for the initial treatment of patients with advanced stages of lung cancer.

This medicationmay be prescribed if you have advanced-stage lung cancer, if your disease has responded to treatment or if it remains unchanged after initial chemotherapy.

This medicationmay also be administered for the treatment of patients with advanced stages of lung cancer whose disease has progressed, who have already received initial chemotherapy.

Do not usethis medication

• if you are allergic to pemetrexed or any of the other components of this medication (listed in section 6).
• if you are breastfeeding, you must stop breastfeeding during treatment withthis medication.
• if you have recently received or are to receive the yellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before this medication is administered to you.

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

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 this medication. Your doctor may decide to change your dose or delay treatment depending on your overall 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 the 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 this medication.

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

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

If you have fluid accumulation around your lung, your doctor may decide to drain the fluid before administering this medication to you.

Children and adolescents

No relevant data is available on the use of this medication in the pediatric population.

Other medications and Pemetrexed Ever Pharma

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication, including pain or anti-inflammatory medications (such as non-steroidal anti-inflammatory drugs, or NSAIDs), including those obtained without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your infusion of this medication and/or your renal function, your doctor will advise you on which medications you can use and when. If you are unsure, consult your doctor or pharmacist to see if any medication you are taking is an NSAID.

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

Like other chemotherapy medications, it is not recommended to use this medication with live, attenuated vaccines. Whenever possible, inactivated vaccines should be used.

Pregnancy

If you are pregnant, think you may be pregnant, or intend to become pregnant, inform your doctor. During pregnancy, the use of this medication should be avoided. Your doctor will inform you of the possible risks of taking this medication during pregnancy. Women should use effective contraceptive methods during treatment with this medication and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with this medication, breastfeeding should be stopped.

Fertility

Men are advised not to father a child during and for 3 months after treatment with this medication, and therefore should use effective contraceptive methods during and for 3 months after treatment with this medication. If you wish to have a child during treatment or in the 3 months following treatment, consult your doctor or pharmacist. Pemetrexed Ever Pharma may affect your ability to have children. Talk to your doctor about sperm conservation before starting your treatment.

Driving and operating machines

This medication may make you feel tired. Be careful when driving a vehicle or operating machines.

This medicationcontains sodium

This medication contains 96.6 mg of sodium (main component of table salt/for cooking) in each dose (500 mg of pemetrexed per square meter of body surface area). This is equivalent to 4.8% of the maximum daily sodium intake recommended for an adult.

This medication will be administered by a healthcare professional. The dose of this medication is 500 milligrams per square meter of the surface area of your body. 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 overall condition. The hospital pharmacist, nurse, or doctor will have mixedpemetrexedwith a solution of 9 mg/ml (0.9%) sodium chloride or a 5% glucose solution for injection before it is administered to you.

You will always receive this medication through an infusion (IV line) in one of your veins. The infusion will last at least 10 minutes.

When using this medication 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 the infusion ofpemetrexedhas finished. The cisplatin infusion lasts approximately two hours.

You should normally receive your infusion once every 3 weeks.

Additional medication:

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

Vitamin supplement: Your doctor will prescribe you 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 this medication. You must take at least 5 doses during the 7 days before the first dose of this medication. You must continue taking folic acid for 21 days after the last dose of this medication. You will also receive an injection of vitamin B12 (1,000 micrograms) the week before administration of this medication and approximately every 9 weeks (corresponding to 3 treatment cycles with this medication). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

During treatment, a close follow-up of your disease will be performed, which involves periodic blood tests to check, among other things, liver and kidney function. Depending on the results obtained in these tests, it may be possible to modify your dose or postpone your 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 should 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 common). Infections (sepsis) can be serious and cause death.
• If you start to feel chest pain (frequent) or your heart rate is faster (rare).
• If you have pain, redness, swelling, or sores in your mouth (very common).
• Allergic reaction: if you develop hives (very common), burning sensation, or itching (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 common).
• 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 common).
• 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 pulmonary veins).

Other side effects with this medicinemay include:

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

• Infection
• Pharyngitis (sore throat)
• Low count of neutrophil granulocytes (a type of white blood cell)
• Low white blood cell count
• Low hemoglobin levels
• Pain, redness, swelling, or sores in the mouth
• Loss of appetite
• Vomiting
• Diarrhea
• Nausea
• Skin rash
• Scaly skin
• Abnormal blood test results showing reduced kidney function
• Asthenia (fatigue)

Frequent (may affect up to 1 in 10 people)

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

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

Frequency unknown: the frequency cannot be estimated from available data

You may experience some of these symptoms 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 type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the 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.

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the box after CAD. The expiration date is the last day of the month indicated.

Do not freeze.

Infusion solution: chemical and physical stability has been demonstrated during the use of the pemetrexed infusion solution for 28 days in refrigeration (2 °C to 8 °C) and for 7 days between 20°C and 30 °C.

From a microbiological point of view, the product must be used immediately. If not used immediately, the time and conservation conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2 °C-8 °C, unless the dilution has been performed under controlled and validated sterile conditions.

This medicationshould not be used if particles are observed.

This medication is for single use only.

Any unused medication or material derived from its use should be disposed of in accordance with local regulations.

Pemetrexed Ever Pharma Composition

The active ingredient is pemetrexed.

Each milliliter of concentrate contains 25 mg of pemetrexed (as pemetrexed disodium).

Each 4 ml vial of concentrate contains 100 mg of pemetrexed (as pemetrexed disodium).

Each 20 ml vial of concentrate contains 500 mg of pemetrexed (as pemetrexed disodium).

Each 40 ml vial of concentrate contains 1000 mg of pemetrexed (as pemetrexed disodium).

The other components are trometamol, monothioglycerol, citric acid, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injection preparations.

A further dilution by a healthcare professional is required before administration.

Product Appearance and Packaging Content

Pemetrexed Ever Pharma concentrate for solution for infusion is a clear, transparent, slightly yellow or yellow-green solution.

This medicine is presented in a colourless glass vial with a rubber stopper and an aluminium cap with a plastic flip-off. The vials may be covered or not with a protective sleeve.

Each package of this medicine contains one vial.

Packaging sizes:

Package with 1 vial of 4 ml vial (100 mg/4 ml)

Package with 1 vial of 20 ml vial (500 mg/20 ml)

Package with 1 vial of 40 ml vial (1000 mg/40 ml)

Only some packaging sizes may be commercially available.

Marketing Authorization Holder

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Manufacturer

EVER Pharma Jena GmbH

Otto Schott Str. 15

07747 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

For further information about this medicine, please contact the local representative of the marketing authorization holder:

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area with the following names:

AustriaPemetrexed EVER Pharma 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

BelgiumPemetrexed EVER Pharma 25 mg/ml concentraat voor oplossing voor infusie /solution à diluer pour perfusion /Konzentrat zur Herstellung einer Infusionslösung

Czech RepublicPemetrexed EVER Pharma 25 mg/ml koncentrát pro infuzní roztok

GermanyPemetrexed EVER Pharma 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

DenmarkPemetrexed EVER Pharma 25 mg/ml koncentrat til infusionsvæske, opløsning

SpainPemetrexed EVER Pharma 25 mg/ml concentrado para solución para perfusión

FinlandPemetrexed EVER Pharma 25 mg/ml infuusiokonsentraatti, liuosta varten

FrancePemetrexed EVER Pharma 25 mg/ml, solution à diluer pour perfusion

CroatiaPemetrexed EVER Pharma 25 mg/ml koncentrat za otopinu za infuziju

HungaryPemetrexed EVER Pharma 25 mg/ml koncentrátum oldatos infúzióhoz

IrelandPemetrexed EVER Pharma 25 mg/ml concentrate for solution for infusion

ItalyPemetrexed EVER Pharma 25 mg/ml concentrato per soluzione per infusione

NetherlandsPemetrexedEVER Pharma 25 mg/ml concentraat voor oplossing voor infusie

NorwayPemetrexed EVER Pharma 25 mg/ml konsentrat til infusjonsvæske, oppløsning

PolandPemetrexed EVER Pharma 25 mg/ml koncentrat do sporzadzania roztworu do infuzji

PortugalPemetrexed EVERPharma 25 mg/ml Concentrado para solução para perfusão

RomaniaPemetrexed EVER Pharma 25 mg/ml concentrat pentrusolutie perfuzabila

SwedenPemetrexed EVER Pharma 25 mg/mlkoncentrat till infusionsvätska, lösning

SloveniaPemetreksed EVER Pharma 25 mg/mlkoncentrat za raztopino za infundiranje

SlovakiaPemetrexed EVER Pharma 25 mg/ml infúzny koncentrát

Last review date of thisleaflet: January 2025

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

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This information is intended solely for healthcare professionals:

Please consult the Technical Dossier for complete information.

Pregnant women should not handle this medicine.

Instructions for use and handling and disposal

1. Use aseptic techniques when diluting pemetrexed for intravenous infusion administration.

2. Calculate the dose and number ofthis medicinenecessary.

3. The appropriate volume ofthis medicinePharma must be diluted to 100 ml with a 9 mg/ml (0.9%) sodium chloride solution or a 5% glucose solution for injection, without preservatives, and must be administered as an intravenous infusion over 10 minutes.

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

This medicine contains trometamol as an excipient. Trometamol is incompatible with cisplatin, which degrades it. This medicine should not be mixed with others, except as mentioned in section 6.6. After administration of this medicine, the intravenous routes must be purged.

5. Parenteral medicines must be visually inspected before administration to discard the appearance of particles or alteration of color. If particles are observed, the medicine should not be administered.

6. Pemetrexed solutions are for single use. The medicine and unused material must be disposed of in accordance with local regulations.

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 solutions for infusion. The use of gloves is recommended for handling. 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, they should be washed with abundant water. Pemetrexed is not a vesicant. 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 non-vesicant drugs.