Leaflet: information for the user

Pemetrexed Ebewe 25 mg/ml concentrate for solution for infusion

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

1. What isPemetrexed Ebeweand what is it used for

2. What you need to knowbeforeyou are givenPemetrexed Ebewe

3. How to usePemetrexed Ebewe

4. Possible side effects

5. Storage ofPemetrexed Ebewe

6. Contents of the pack and additional information

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

Pemetrexed can be administered along with cisplatin, another anticancer medication, as treatment for malignant pleural mesothelioma, a type of cancer that affects the lung lining, in patients who have not received prior chemotherapy.

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

Pemetrexed 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 can also be administered for the treatment of patients in advanced stages of lung cancer whose disease has progressed after receiving initial chemotherapy treatment.

This medication is only used in adults.

No usePemetrexed Ebewe:

• 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 with pemetrexed,
• if you have recently received or are to receive the yellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before you are administered Pemetrexed Ebewe.

If you have or have had kidney problems, consult 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 evaluate if your renal and hepatic function is sufficient and to evaluate if you have enough blood cells to receive pemetrexed. Your doctor may decide to change your dose or delay treatment based 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 your doctor, as there may be an early or late reaction between the radiation and pemetrexed.

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

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

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

Children and adolescents

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

Other medications and Pemetrexed Ebewe

Inform your doctor if you are using pain or anti-inflammatory medications (such as nonsteroidal anti-inflammatory drugs or 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 pemetrexed infusion and/or your renal function, your doctor will advise you 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.

Inform your doctor or hospital pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription.

Pregnancy,breastfeedingand fertility

Pregnancy

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

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with pemetrexed, breastfeeding should be interrupted.

Fertility

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

Driving and operating machinery

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

Pemetrexed Ebewe contains sodium and propylene glycol

Pemetrexed Ebewe 100 mg (vial with 4 ml)

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

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

Pemetrexed Ebewe 500 mg (vial with 20 ml)

This medication contains 55.6 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 3% of the maximum daily sodium intake recommended for an adult.

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

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

This medication contains 111.2 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 6% of the maximum daily sodium intake recommended for an adult.

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

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

The dose of pemetrexed is 500 milligrams per square meter of your body surface. 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 delayed depending on your blood cell count and overall condition. The hospital pharmacist, nurse, or doctor will have mixed the pemetrexed solution with a sodium chloride solution 9 mg/ml (0.9%) or glucose solution 50 mg/ml (5%) before administering it to you.

You will always receive pemetrexed through a drip in one of your veins. The drip will last approximately 10 minutes.

When using Pemetrexed Ebewe 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 a drip in one of your veins and is given approximately 30 minutes after the pemetrexed drip has finished. The cisplatin drip will last approximately 2 hours.

You should normally receive your drip once every three 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, on the same day, and the day after treatment with pemetrexed. This medication is given 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 should take once a day while taking pemetrexed. You should take at least five doses during the seven days before the first dose of pemetrexed. You should continue taking folic acid for 21 days after the last dose of pemetrexed. You will also receive an injection of vitamin B12(1,000 micrograms) the week before pemetrexed administration and approximately every 9 weeks (corresponding to 3 treatment cycles with pemetrexed). Vitamin B12and folic acid are given to reduce possible toxic effects of cancer treatment.

If you have any other questions about the use of thismedication, ask your doctororfarmacéutic.

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 or very frequent, respectively): 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 severe and cause death.
• if you start to feelpaininthechest(frequent) or the heart rate is faster (rare),
• if you havepain,redness,swellingorsoresinthemouth(very frequent),
• allergic reaction: if you develophives(very frequent),burning or itching sensationor(frequent), orfever(frequent). In rare cases, skin reactions can be severe and cause death.

Contact your doctor if you experiencesevere rash, itching, or blisters(Stevens-Johnson syndrome or Toxic Epidermal Necrolysis).

• If you feelfatiguedordizzy, if you haveshortness of breathor are pale (since you may have fewer hemoglobin than normal, which is very frequent),
• if you experiencebleedingfromthegums,noseormouthor any bleeding that does not stop, pink or red urine, or unexpected bruises (since you may have fewer platelets than normal, which is very frequent),
• if you experience sudden difficulty breathing,intense chest painor coughing up blood in the sputum (rare) (which may indicate that there is a blood clot in the pulmonary veins).

The side effects of pemetrexed may include:

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

-infection,

-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 test results showing reduced kidney function,

-asthenia (fatigue).

Frequent(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,
• fluid loss,
• alterations in taste,
• damage to motor nerves that can cause muscle weakness and atrophy (emaciation mainly in arms and legs),
• damage to sensory nerves that can cause numbness, burning sensation, and unstable gait,
• dizziness,
• conjunctival inflammation or swelling (membrane covering the eyelids and covering the white part of the eye),
• dry eyes,
• tearful eyes,
• dryness of the conjunctiva (membrane inside 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 (condition affecting the heart's pumping ability),
• irregular heart rhythm,
• indigestion,
• constipation,
• abdominal pain,
• liver: increased substances in the blood produced by the liver,
• skin darkening,
• itching skin,
• skin rash on the body where each lesion resembles a target,
• hair loss,
• urticaria,
• renal failure,
• reduced kidney function,
• fever,
• pain,
• excess fluid in the body tissue causing swelling,
• chest pain,
• inflammation and ulceration of the mucous membranes lining the digestive tract.

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 an area previously irradiated

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 fatal)
• Toxic Epidermal Necrolysis (a type of severe skin reaction that can be fatal)
• autoimmune disorder causing skin eruptions and blisters on the legs, arms, and abdomen
• inflammation of the skin characterized by the presence of blisters filled with fluid
• skin fragility, blisters, and erosions, and skin scars
• redness, pain, and swelling mainly in the lower limbs
• inflammation of the skin and subcutaneous fat (pseudocelulitis)
• inflammation of the skin (dermatitis)
• the skin becomes inflamed, itches, reddens, cracks, and becomes rough
• intensely itchy spots

Not known:the frequency cannot be estimated from available data

• a type of diabetes primarily caused by kidney disease
• renal disorder involving the death of tubular epithelial cells that form the renal tubules.

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 theSistema Español de Farmacovigilancia de medicamentos de Uso Humano: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 usethis medicationafter the expiration date that appears on the packaging andthe labelafter “EXP/USE BY”.The expiration date is the last day of the month indicated.

Unopened vial

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

After the first opening

The product must be used immediately. All 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 point of view, this medication must be used immediately after opening. If not used immediately, the storage times and conditions in use are the responsibility of the user and will not exceed 24 hours at temperatures between 2°C and 8°C, unless the dilution was made in a place with controlled and validated aseptic conditions.

Medications should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Pemetrexed Ebewe

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

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

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

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

One vial containing 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 injection preparations.

Appearance of the product and contents of the package

Pemetrexed Ebewe is aconcentrate for solution for infusion. It is a transparent, colorless or yellowish or yellowish green solution. Practically particle-free solution.

Pemetrexed Ebewe is packaged in type I glass vials with a bromobutyl rubber stopper and an aluminum crimp cap with a blue clear plastic flip-off cap.

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

Each package contains 1 vial (with or without packaging).

Only some package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Responsible for manufacturing

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

Mondseestrasse 11

4866 Unteracham Attersee

Austria

or

Fareva Unterach GmbH

Mondseestrasse 11

4866 Unteracham Attersee

Austria

Last review date of thisleaflet:February 2025.

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

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This information is intended solely for healthcare professionals:

Special precautions for disposal and other manipulations.

Pemetrexed solutions are for single use. The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic agents.

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

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

1. Pemetrexed should be diluted to 100 ml with sodium chloride 9 mg/ml (0.9%) solution (without preservatives) or with 5% glucose solution (without preservatives) and administered as an intravenous infusion over 10 minutes.

1. The pemetrexed solution for infusion prepared according to the indications above is compatible with polyolefin infusion systems and bags.

1. Parenteral medications should be visually inspected prior to administration to discard the appearance of particles or alteration of color. If particles are observed, the medication should not be administered.

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, 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.

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