Pemetrexed EBEWE 25 mg/ml concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Pemetrexed Ebewe 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, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

Pemetrexed Ebewe is a medicine used for the treatment of cancer.

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

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

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

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

This medicine is only used in adults.

2. What you need to know before you are given Pemetrexed Ebewe

Do not use Pemetrexed Ebewe:

• 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 interrupt breastfeeding during treatment with pemetrexed,
• 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 Pemetrexed Ebewe.

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

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 pemetrexed. 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 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 delayed interaction between radiation and pemetrexed.

If you have recently been vaccinated, please consult your doctor, as this may potentially cause a negative reaction with pemetrexed.

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 pemetrexed.

Children and adolescents

This medicine should not be used in children or adolescents, as there is no experience with this medicine in children and adolescents under 18 years of age.

Other medicines and Pemetrexed Ebewe

Tell your doctor if you are taking medicines for pain or inflammation (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 pemetrexed infusion 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.

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 taking, have recently taken, or might need to take any other medicines, including those obtained 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. Use of pemetrexed during pregnancy should be avoided. Your doctor will inform you of the potential risks of using pemetrexed during pregnancy. Women must use effective contraception during treatment with pemetrexed and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding must be interrupted during treatment with pemetrexed.

Fertility

Male patients are advised not to father a child during and for 3 months after treatment with pemetrexed, and therefore should use effective contraception during and for 3 months after treatment with pemetrexed. If you wish to father a child during treatment or within 3 months after treatment, seek advice from your doctor or pharmacist. Pemetrexed may affect your ability to have children. Consult your doctor for information about sperm preservation before starting treatment.

Driving and use of machines

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

Pemetrexed Ebewe contains sodium and propylene glycol

Pemetrexed Ebewe 100 mg (vial with 4 ml)

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

This medicine contains 200 mg of propylene glycol in each vial.

Pemetrexed Ebewe 500 mg (vial with 20 ml)

This medicine contains 55.6 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 3% of the maximum daily recommended sodium intake for an adult.

This medicine contains 1,000 mg of propylene glycol in each vial.

Pemetrexed Ebewe 1,000 mg (vial with 40 ml)

This medicine contains 111.2 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 6% of the maximum daily recommended sodium intake for an adult.

This medicine contains 2,000 mg of propylene glycol in each vial.

3. How to use Pemetrexed Ebewe

Pemetrexed must be administered only under the supervision of a qualified physician experienced in the use of antineoplastic chemotherapy.

The dose of pemetrexed 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 value to determine the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell counts and your overall condition. The hospital pharmacist, nurse, or doctor will have mixed the pemetrexed solution with an infusion solution of sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) prior to administration.

You will always receive pemetrexed as an intravenous infusion into one of your veins. The infusion will last approximately 10 minutes.

When using Pemetrexed Ebewe in combination with cisplatin

Your doctor or hospital pharmacist will calculate your required dose based on your height and weight. Cisplatin is also administered as an intravenous infusion and is given approximately 30 minutes after the pemetrexed infusion has finished. The cisplatin infusion will last approximately 2 hours.

You will normally receive your infusion once every three 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 pemetrexed treatment. This medication is given to reduce the frequency and severity of skin reactions that may occur during your cancer treatment.

Vitamin supplementation: Your doctor will prescribe oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms), to be taken once daily while you are receiving pemetrexed. You must take at least five doses during the seven days prior to your first pemetrexed dose. You should continue taking folic acid for 21 days after your last dose of pemetrexed. Additionally, you will receive an injection of vitamin B12 (1,000 micrograms) during the week before the first pemetrexed administration and then approximately every 9 weeks (corresponding to 3 treatment cycles of pemetrexed). Vitamin B12 and folic acid are administered to reduce the potential toxic effects of cancer treatment.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

• fever or infection (frequent or very frequent, respectively): if you have a temperature of 38 °C or higher, sweating, or other signs of infection (as you may have lower than normal white blood cells, which is very common). Infections (sepsis) can be severe and may cause death.
• if you begin to feel chest pain (frequent) or your heartbeat 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 or itching sensation (frequent), or fever (frequent). In rare cases, skin reactions may be severe and may cause death.

Contact your doctor if you develop 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 look pale (due to lower than normal hemoglobin levels, which is very common),
• if you experience bleeding from 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 lung veins).

Adverse effects with pemetrexed 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,
• blood test abnormalities 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,
• altered sense of taste,
• 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 pain (burning sensation), 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 membrane lining the inner eyelids and covering the white part of the eye) and cornea (transparent layer in front of the iris and pupil),
• eyelid swelling,
• 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 liver-produced chemicals in the blood,
• increased skin pigmentation,
• skin itching,
• rash in which each lesion resembles a target (target-like lesions),
• 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,
• increased heart rate,
• poor blood distribution to the limbs,
• obstruction in one of the pulmonary arteries in the lungs,
• inflammation and scarring of the lung mucosa with breathing problems,
• bright red blood loss from the anus,
• 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,
• skin redness,
• 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 type of severe skin and mucous membrane reaction that may be fatal),
• toxic epidermal necrolysis (a type of severe skin reaction that may 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, blistering, erosions, and scarring,
• 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.

Not known: frequency cannot be estimated from available data

• A type of diabetes mainly resulting from kidney disease,
• kidney disorder involving death of tubular epithelial cells forming the renal tubules,
• increased urinary excretion,
• thirst and increased water intake,
• hypernatremia: elevated sodium levels in blood.

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 Ebewe

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

Do not use this medicine after the expiry date stated on the container and label, following “CAD/EXP”. The expiry date refers to the last day of the month indicated.

Unopened vial

Do not store above 25°C. Keep in the original packaging to protect from light.

After first opening

The product should be used immediately. Any unused portions must be discarded.

After dilution

Vial with 100 mg

The stability of the infusion solution has been demonstrated for 3 days at temperatures between 2°C and 8°C, protected from light.

Vial with 500 mg and vial with 1,000 mg

The stability of the infusion solution has been demonstrated for 7 days at room temperature, protected from light, and for 14 days in the refrigerator, between 2°C and 8°C, protected from light.

From a microbiological standpoint, this medicine should be used immediately after opening. If not used immediately, the storage times and conditions during use are the responsibility of the user and should not exceed 24 hours at temperatures between 2°C and 8°C, unless the dilution was carried out under controlled and validated aseptic conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Pemetrexed Ebewe

The active substance is pemetrexed (as pemetrexed disodium hemipentahydrate).

One ml of concentrate for solution for infusion contains 25 mg of pemetrexed (as pemetrexed disodium hemipentahydrate).

One vial with 4 ml contains 100 mg of pemetrexed (as pemetrexed disodium hemipentahydrate).

One vial with 20 ml contains 500 mg of pemetrexed (as pemetrexed disodium hemipentahydrate).

One vial with 40 ml contains 1,000 mg of pemetrexed (as pemetrexed disodium hemipentahydrate).

The other components are sodium thiosulfate pentahydrate (E 539), propylene glycol (E 1520), hydrochloric acid (for pH adjustment), sodium hydroxide (E 524) (for pH adjustment), and water for injections.

Appearance of the product and contents of the pack

Pemetrexed Ebewe is a concentrate for solution for infusion. It is a clear, colourless to yellow or yellowish-green solution, practically free from particles.

Pemetrexed Ebewe is supplied in Type I glass vials with a bromobutyl rubber stopper and an aluminium seal with a light blue plastic flip-off cap.

Each vial contains 4 ml, 20 ml or 40 ml of concentrate for solution for infusion.

Each pack contains 1 vial (with or without overwrap).

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Ebewe Pharma Ges.m.b.H. Nfg.KG

Mondseestrasse 11

4866 Unterach am Attersee

Austria

or

Fareva Unterach GmbH

Mondseestrasse 11

4866 Unterach am Attersee

Austria

Date of the most recent revision of this summary: July 2025.

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

This information is intended for healthcare professionals only:

Special precautions for disposal and other handling.

Solutions of pemetrexed are for single use only. Any unused medicine and materials that have come into contact with it must be disposed of in accordance with local regulations for cytotoxic agents.

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

2. Calculate the required dose and number of pemetrexed vials needed. Each vial contains an overage of pemetrexed to facilitate administration of the required nominal amount.

3. The appropriate volume of pemetrexed should be diluted to 100 ml with 9 mg/ml (0.9%) sodium chloride infusion solution (without preservatives) or with 50 mg/ml (5%) glucose infusion solution (without preservatives) and administered as an intravenous infusion over 10 minutes.

4. The pemetrexed infusion solution prepared as described above is compatible with polyolefin infusion systems and bags.

5. Parenteral medicines should be visually inspected before administration to check for the presence of particles or discoloration. If particles are observed, the medicine must not be administered.

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