Pemetrexed Ever Pharma 25 mg/ml concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

Read the entire 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, ask your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

2. What you need to know before using Pemetrexed Ever Pharma

3. How to use Pemetrexed Ever Pharma

4. Possible side effects

5. Storage of Pemetrexed Ever Pharma

6. Contents of the pack and other information

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

This medicine is used for the treatment of cancer. It contains the active substance pemetrexed. Pemetrexed belongs to a group of medicines known as folic acid analogues and interferes with processes essential for cell division.

This medicine may be given together with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a form of cancer affecting the lining of the lung, in patients who have not previously received chemotherapy.

This medicine may also be given, together with cisplatin, as initial treatment for patients with advanced-stage lung cancer.

This medicine may be prescribed to you if you have advanced-stage lung cancer and your disease has responded to treatment or remained stable after initial chemotherapy.

This medicine may also be given for the treatment of patients with advanced-stage lung cancer whose disease has progressed after prior initial chemotherapy treatment.

2. What you need to know before using Pemetrexed Ever Pharma

Do not use this medicine

• if you are allergic to pemetrexed or to 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 received or are about to receive the yellow fever vaccine.

Warnings and precautions

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

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

Before each infusion, you will need to provide blood samples to assess whether your kidney and liver function are adequate and to evaluate whether you have sufficient blood cells to receive this medicine. Your doctor may decide to adjust 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 will administer appropriate treatment before and after cisplatin to prevent vomiting.

If you have received or are about to receive radiotherapy, please consult your doctor, as there may be an early or delayed interaction between radiation and this medicine.

If you have recently been vaccinated, please consult your doctor, as vaccination may cause adverse effects when combined with this medicine.

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

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

Children and adolescents

There is no relevant data available on the use of this medicine in the pediatric population.

Other medicines and Pemetrexed Ever Pharma

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including pain or anti-inflammatory medicines (swelling), such as medicines known as “non-steroidal anti-inflammatory drugs” (NSAIDs), including those obtained without a prescription (such as ibuprofen). There are many types of NSAIDs with different durations of action. Based on the date of your scheduled infusion of this medicine and/or your kidney function status, your doctor will advise you which medicines you can take and when. If you are unsure, consult your doctor or pharmacist to determine whether 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.

As with other chemotherapeutic agents, the use of this medicine together with live attenuated vaccines is not recommended. Inactivated vaccines should be used whenever possible.

Pregnancy

If you are pregnant, think you might 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.

Lactation

If you are breastfeeding, inform your doctor.

Breastfeeding must be discontinued during treatment with this medicine.

Fertility

Male patients are advised not to father a child during treatment and for 3 months after treatment with this medicine, and therefore must use effective contraception during and for 3 months after treatment. If you wish to father a child during treatment or within 3 months after treatment, seek advice from your doctor or pharmacist. Pemetrexed Ever Pharma may affect your ability to have children. Speak with your doctor for advice on sperm preservation before starting treatment.

Driving and use of machines

This medicine may make you feel tired. Be cautious when driving or operating machinery.

This medicine contains sodium

This medicine contains 96.6 mg of sodium (the main component of table/cooking salt) per dose (500 mg of pemetrexed per square meter of body surface area). This corresponds to 4.8% of the maximum daily sodium intake recommended 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 determine the correct dose for you. This dose may be adjusted or the treatment may be delayed depending on your blood cell counts 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 administration.

You will always receive this medicine as an intravenous infusion (drip) into 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 by intravenous infusion and is given approximately 30 minutes after the pemetrexed infusion is completed. The cisplatin infusion lasts approximately two 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 daily) that you must take the day before, the day of, and the day after treatment with this medicine. Your doctor prescribes 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 containing folic acid (350 to 1,000 micrograms) to be taken once daily while you are receiving this medicine. You must take at least 5 doses during the 7 days prior to your first dose of this medicine. You should continue taking folic acid for 21 days after your last dose of this medicine. Additionally, you will receive an injection of vitamin B12 (1,000 micrograms) during the week before administration of this medicine, and then approximately every 9 weeks (corresponding to 3 treatment cycles with this medicine). Vitamin B12 and folic acid are given to reduce potential toxic effects of cancer treatment.

During treatment, your disease will be closely monitored, including periodic blood tests to check, among other things, liver and kidney function. Based on the results of these tests, your dose may be modified or your treatment postponed.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse 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 (as you may have fewer white blood cells than normal, which is very common). Infections (sepsis) can be severe and may lead to death.
• If you begin to feel chest pain (frequent) or your heart rate becomes faster (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), burning sensation or itching (common), or fever (common). Skin reactions may rarely be severe and may be life-threatening. Contact your doctor if you develop a severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, are short of breath, or look pale (due to lower than normal hemoglobin levels, which is very common).
• 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 lower than normal platelet count, which is very common).
• If you suddenly experience difficulty breathing, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the veins of the lungs).

Other adverse effects with this medicine may include:

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

• Infection
• Pharyngitis (sore throat)
• Low neutrophil granulocyte count (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 tests showing reduced kidney function
• Asthenia (tiredness)

Common (may affect up to 1 in 10 people)

• Blood infection
• Fever with low neutrophil granulocyte count (a type of white blood cell)
• Low platelet count
• Allergic reaction
• Loss of body fluids
• Changes in taste sensation
• Motor nerve damage that may cause muscle weakness and atrophy (wasting, mainly in arms and legs)
• Sensory nerve damage that may cause loss of sensation, burning (burning pain), and unsteady gait
• Dizziness
• Inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye)
• Dry eyes
• Watery eyes
• Dryness of the conjunctiva (the inner membrane of the eyelids and covering the white part of the eye) and cornea (transparent layer in front of the iris and pupil)
• Swelling of the eyelids
• Eye disorder with dryness, tearing, irritation, and/or pain
• Heart failure (a condition affecting the heart muscle'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 where each lesion resembles a target
• Hair loss
• Hives
• Kidney failure
• Reduced kidney function
• Fever
• Pain
• Excess fluid in body tissues causing swelling
• Chest pain
• Inflammation and ulceration of the mucous membranes lining the digestive tract internally

Uncommon (may affect up to 1 in 100 people)

• Reduction in red blood cells, white blood cells, and platelets
• Ischemia or lack of blood supply
• Ischemia due to blockage of a cerebral artery
• Intracranial bleeding
• Angina (chest pain caused by reduced blood flow to the heart)
• Infarction
• Narrowing or blockage of the coronary arteries
• Abnormal heart rhythm
• Poor blood distribution to the extremities
• Blockage in one of the pulmonary arteries in the lungs
• Inflammation and scarring of the lung mucosa with breathing problems
• Bright red rectal bleeding
• Bleeding in the gastrointestinal tract
• Intestinal perforation
• Inflammation of the esophageal mucosa
• Inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only in combination with cisplatin)
• Inflammation, edema, erythema, and erosion of the esophageal mucosal surface caused by radiotherapy
• Lung inflammation caused by radiotherapy

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
• Skin rash developing 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 severe type of skin and mucous membrane reaction that can be fatal)
• Toxic epidermal necrolysis (a severe type of skin reaction that can be fatal)
• Autoimmune disorder causing skin rashes and blisters on the legs, arms, and abdomen
• Skin inflammation characterized by the presence of fluid-filled blisters
• Skin fragility, blisters, erosions, and scarring of the skin
• Redness, pain, and swelling mainly in the lower limbs
• Inflammation of the skin and underlying fat (pseudocellulitis)
• Skin inflammation (dermatitis)
• Skin becomes inflamed, itchy, red, cracked, and rough
• Intensely itchy spots

Frequency not known: frequency cannot be estimated from available data

• A type of diabetes primarily resulting from kidney disease
• Kidney disorder involving death of tubular epithelial cells that form the renal tubules

You may experience one or more of these symptoms and/or conditions. You should inform your doctor as soon as you begin to experience any of these adverse effects.

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

Reporting of adverse effects

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

5. Storage of Pemetrexed Ever Pharma

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

Do not use this medicine after the expiry date stated on the label and the carton after EXP. The expiry date refers to the last day of the month indicated.

Do not freeze.

Infusion solution: Chemical and physical in-use stability has been demonstrated for the pemetrexed infusion solution for 28 days when refrigerated (between 2 °C and 8 °C) and for 7 days between 20 °C and 30 °C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and should not exceed 24 hours at 2 °C–8 °C, unless the dilution was carried out under controlled and validated aseptic conditions.

Do not use this medicine if particles are observed.

This medicine is for single use only.

Any unused medicine or waste materials resulting from its use should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

Composition of Pemetrexed Ever Pharma

The active substance is pemetrexed.

Each millilitre 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 tromethamine, monothioglycerol, citric acid, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) and water for injections.

Further dilution by a healthcare professional is required before administration.

Appearance of the product and contents of the pack

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

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

Each pack contains one vial.

Pack sizes:

Pack containing 1 vial of 4 ml (100 mg/4 ml)

Pack containing 1 vial of 20 ml (500 mg/20 ml)

Pack containing 1 vial of 40 ml (1000 mg/40 ml)

Only certain pack sizes may be marketed.

Marketing Authorisation 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 Authorisation Holder:

EVER Pharma Therapeutics Spain, S.L.
C/Toledo 170
28005 Madrid
Spain

This medicine is authorised 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 latest review of this summary: January 2025

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

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This information is intended for healthcare professionals only:

Please refer to the Summary of Product Characteristics for complete information.

Pregnant women must not handle this medicine.

Instructions for use, handling and disposal

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

2. Calculate the required dose and number of vials of this medicine needed.

3. The appropriate volume of this medicine should be diluted to 100 ml with either 9 mg/ml (0.9%) sodium chloride solution or 5% glucose solution for injection, both without preservatives, and administered as an intravenous infusion over 10 minutes.

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

This medicine contains tromethamine as excipient. Tromethamine is incompatible with cisplatin, as it degrades cisplatin. This medicine must not be mixed with other medicinal products except those mentioned in section 6.6. Intravenous lines must be flushed after administration of this medicine.

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

2. Pemetrexed solutions are for single use only. Unused medicine and waste 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 handling and preparing pemetrexed solutions for infusion. Use of gloves is recommended. If pemetrexed solutions come into contact with the skin, wash immediately and thoroughly with soap and water. If pemetrexed solutions come into contact with mucous membranes, flush thoroughly with 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 managed according to standard clinical practice for non-vesicant drugs.