PEMETREXED EVER PHARMA 25 mg/mL concentrate for infusion solution

Introduction

Package Leaflet:information for theuser

Pemetrexed Ever Pharma 25 mg/ml concentrate for solution for infusion

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

• Keep this leaflet, you may need to read it again.
• 1. 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 Pemetrexed Ever Pharma is and what it is used for
2. What you need to know before you use Pemetrexed Ever Pharma
3. How to use Pemetrexed Ever Pharma
4. Possible side effects

5 Conservation of Pemetrexed Ever Pharma

1. Contents of the pack and further information

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

This medicine is used to treat cancer. It contains the active substance pemetrexed. Pemetrexed belongs to a group of medicines known as folate analogs and disrupts processes that are essential for cell division.

This medicine 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.

This medicine can also be given, along with cisplatin, for the initial treatment of patients with advanced stages of lung cancer.

This medicine 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.

This medicine can also be given for the treatment of patients with 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 Ever Pharma

Do not usethis medicine

• if you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding, you must stop breastfeeding during treatment with this medicine.
• if you have recently been given the yellow fever vaccine or are going to be given it.

Warnings and precautions

Talk to your doctor or hospital pharmacist before you are given this medicine.

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

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 this medicine. 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 there may be an early or late reaction between radiation and this medicine.

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

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 drain the fluid before administering this medicine to you.

Children and adolescents

No relevant data are available on the use of this medicine in the pediatric population.

Other medicines and Pemetrexed Ever Pharma

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including 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 infusion of this medicine 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 unsure, 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.

As with other chemotherapeutic medicines, the use of this medicine with live attenuated vaccines is not recommended. Whenever possible, inactivated vaccines should be used.

Pregnancy

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

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding should be discontinued during treatment with this medicine.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with this medicine and must use effective contraceptive methods during and up to 3 months after treatment with this medicine. 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 using machines

This medicine may make you feel tired. Be careful when driving a vehicle or using machines.

This medicinecontains sodium

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

3. How to use Pemetrexed Ever Pharma

This medicine will always be administered by a healthcare professional. The dose of this medicine 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 pemetrexed with a 9 mg/ml (0.9%) sodium chloride solution or a 5% glucose solution for injection before it is administered to you.

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

When using this medicine in combination with cisplatin:

Your doctor or 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 of pemetrexed has finished. The cisplatin infusion lasts approximately 2 hours.

You should normally receive your infusion once every 3 weeks.

Additional medication:

Corticosteroids: your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you must take the day before, the same day, and the day after treatment with this medicine. 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 must take once a day while taking this medicine. You must take at least 5 doses during the 7 days before the first dose of this medicine. You must continue taking folic acid during 21 days after the last dose of this medicine. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before administration of this medicine and then approximately every 9 weeks (corresponding to 3 cycles of treatment with this medicine). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

During treatment, close monitoring of your disease will be carried out, which involves periodic blood tests to check, among other things, liver and kidney function. Depending on the results of these tests, your dose may be modified or your treatment may be postponed.

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 serious 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 serious 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 in your sputum (uncommon) (may indicate that there is a blood clot in the lungs).

Other side effects with this medicine may include:

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

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

Common (may affect up to 1 in 10 people)

• Blood infection
• Fever with low neutrophil count (a type of white blood cell)
• Low platelet count
• Allergic reaction
• Loss of body fluids
• Abnormal taste
• Nerve damage that can cause muscle weakness and wasting (mainly in arms and legs)
• Nerve damage that can cause loss of sensation, burning (pain), and unsteady gait
• Dizziness
• Inflammation or swelling of the conjunctiva (membrane that covers the eyelids and the white part of the eye)
• Dry eyes
• Tearing
• Dryness of the conjunctiva (membrane inside the eyelids and covering the white part of the eye) and the cornea (transparent layer in front of the iris and pupil)
• Swelling of the eyelids
• Ocular disorder with dryness, tearing, irritation, and/or pain
• Heart failure (condition that affects the heart's pumping ability)
• Irregular heartbeat
• Indigestion
• Constipation
• Abdominal pain
• Liver: increased levels of chemicals in the blood produced by the liver
• Increased skin pigmentation
• Itching of the skin
• Rash on the body where each lesion resembles a target
• Hair loss
• Hives
• Kidney failure
• Reduced kidney function
• Fever
• Pain
• Excess fluid in the body tissue that causes swelling
• Chest pain
• Inflammation and ulceration of the mucous membranes that line the digestive tract

Uncommon (may affect up to 1 in 100 people)

• Decreased number of red blood cells, white blood cells, and platelets
• Ischemia or lack of blood flow
• Ischemia due to blockage of a cerebral artery
• Intracranial bleeding
• Angina (chest pain caused by reduced blood flow to the heart)
• Heart attack
• Narrowing or blockage of the coronary arteries
• Abnormal heartbeat
• Poor distribution of blood to the limbs
• Blockage in one of the pulmonary arteries in the lungs
• Inflammation and scarring of the lung mucosa with respiratory problems
• Bright red blood loss through the anus
• Bleeding in the gastrointestinal tract
• Perforation of the intestine
• Inflammation of the esophagus mucosa
• Inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)
• Inflammation, edema, erythema, and erosion of the mucous membrane surface of the esophagus caused by radiotherapy
• Radiation-induced lung inflammation

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

• Destruction of red blood cells
• Anaphylactic shock (severe allergic reaction)
• Inflammatory liver disease
• Redness of the skin
• Rash on the skin that develops in a previously irradiated area

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

• Skin and soft tissue infections
• Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that can be life-threatening)
• Toxic epidermal necrolysis (a type of severe skin reaction that can be life-threatening)
• Autoimmune disorder that causes skin rashes and blisters on the legs, arms, and abdomen
• Inflammation of the skin characterized by the presence of blisters that are filled with fluid
• Skin fragility, blisters, and erosions and scarring of the skin
• Redness, pain, and swelling mainly of the lower limbs
• Inflammation of the skin and the fat under the skin (pseudocellulitis)
• Inflammation of the skin (dermatitis)
• The skin becomes inflamed, itchy, red, cracked, and rough
• Itchy patches

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

• A type of diabetes derived mainly from kidney disease
• Kidney disorder that involves the death of the epithelial tubular cells that form the renal tubules

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 effects, talk to your doctor or pharmacist, even if they are 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. Conservation of Pemetrexed Ever Pharma

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 label and carton after EXP. The expiry date is the last day of the month stated.

Do not freeze.

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

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

This medicine should not be used if particles are observed.

This medicine is for single use only.

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

6. Container Content and Additional Information

Composition of Pemetrexed Ever Pharma

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 injectable preparations.

Additional dilution by a healthcare professional is required before administration.

Appearance of the Product and Container Content

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

This medicinal product is presented in a colorless glass vial, with a rubber stopper and an aluminum cap with a plastic flip-off. The vials may or may not be covered by a protective sleeve.

Each pack of this medicinal product contains one vial.

Package sizes:

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

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

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

Not all package sizes may be marketed.

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 medicinal product, please contact the local representative of the marketing authorization holder:

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria Pemetrexed EVER Pharma 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

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

Czech Republic Pemetrexed EVER Pharma 25 mg/ml koncentrát pro infuzní roztok

Germany Pemetrexed EVER Pharma 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Denmark Pemetrexed EVER Pharma 25 mg/ml koncentrat til infusionsvæske, opløsning

Spain Pemetrexed EVER Pharma 25 mg/ml concentrado para solución para perfusión

Finland Pemetrexed EVER Pharma 25 mg/ml infuusiokonsentraatti, liuosta varten

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

Croatia Pemetrexed EVER Pharma 25 mg/ml koncentrat za otopinu za infuziju

Hungary Pemetrexed EVER Pharma 25 mg/ml koncentrátum oldatos infúzióhoz

Ireland Pemetrexed EVER Pharma 25 mg/ml concentrate for solution for infusion

Italy Pemetrexed EVER Pharma 25 mg/ml concentrato per soluzione per infusione

Netherlands Pemetrexed EVER Pharma 25 mg/ml concentraat voor oplossing voor infusie

Norway Pemetrexed EVER Pharma 25 mg/ml konsentrat til infusjonsvæske, oppløsning

Poland Pemetrexed EVER Pharma 25 mg/ml koncentrat do sporzadzania roztworu do infuzji

Portugal Pemetrexed EVER Pharma 25 mg/ml Concentrado para solução para perfusão

Romania Pemetrexed EVER Pharma 25 mg/ml concentrat pentru solutie perfuzabila

Sweden Pemetrexed EVER Pharma 25 mg/ml koncentrat till infusionsvätska, lösning

Slovenia Pemetreksed EVER Pharma 25 mg/ml koncentrat za raztopino za infundiranje

Slovakia Pemetrexed EVER Pharma 25 mg/ml infúzny koncentrát

Date of the last revision of this leaflet: January 2025

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es)

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This information is intended only for healthcare professionals:

Please consult the Summary of Product Characteristics for complete information.

Pregnant women should not handle this medicinal product.

Instructions for use and handling and disposal

1. Use aseptic techniques during the dilution of pemetrexed for administration by intravenous infusion.

1. Calculate the dose and the number of vials of this medicinal product needed.

1. The appropriate volume of this medicinal product should 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 should be administered as an intravenous infusion over 10 minutes.

1. The pemetrexed infusion solution prepared according to the instructions 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.

This medicinal product contains trometamol as an excipient. Trometamol is incompatible with cisplatin, as it degrades cisplatin. This medicinal product should not be mixed with other medicinal products, except those mentioned in section 6.6. After administration of this medicinal product, the intravenous lines should be flushed.

1. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is observed, the medicinal product should not be administered.

1. Pemetrexed solutions are for single use. The medicinal product and unused material should be discarded according to 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 infusion solutions. The use of gloves is recommended. 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 for non-vesicant drugs.