Leaflet: information for the user

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

1. What isPemetrexedTillomedand what it is used for

2. What you need to know before starting to usePemetrexedTillomed

3. How to usePemetrexedTillomed

4. Possible side effects

5. Storage ofPemetrexedTillomed

6. Contents of the pack and additional information

PemetrexedTillomedis a medication used for the treatment of cancer.

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

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

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

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

Do not usePemetrexedTillomed:

-if you areallergic to pemetrexed or any of the other componentsof this medication (listed in section 6).

-if you arebreastfeeding, you must stop breastfeeding during treatment with Pemetrexed Tillomed.

-if you have recently received theyellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before starting to usePemetrexedTillomed.

• if you have had or have kidney problems, as you may not be able to receivePemetrexedTillomed.

Before each infusion, you will need to give blood samples to evaluate if your kidney and liver function is sufficient and to evaluate if you have enough blood cells to receivePemetrexedTillomed. 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, as it may cause an early or late reaction between the radiation andPemetrexedTillomed.

• if you have recently been vaccinated, as it may cause a negative effect withPemetrexedTillomed.

• if you have a heart condition or a history of heart disease.

• if you have fluid accumulation around the lung, your doctor may decide to drain the fluid before administeringPemetrexedTillomed.

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 andPemetrexedTillomed

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

Inform your doctor or pharmacist if you are taking anymedication for pain or inflammation(swelling), such as 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 yourPemetrexedTillomedinfusion and/or your kidney 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, and rabeprazole) used to treat stomach acid and acid reflux.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, inform your doctor. During pregnancy, the use ofPemetrexedTillomedshould be avoided. Your doctor will inform you of the possible risks of takingPemetrexedTillomedduring pregnancy. Women should use effective contraceptive methods during treatment withPemetrexedTillomedand for 6 months after completing treatment.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment withPemetrexedTillomedbreastfeeding should be interrupted.

Fertility

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

Driving and operating machinery

PemetrexedTillomedmay cause fatigue. Be careful if you drive a car or use machines.

Pemetrexed Synthon contains propylene glycol

This medication contains 140 mg of propylene glycol in each 4 ml vial, equivalent to 35 mg/ml

This medication contains 700 mg of propylene glycol in each 20 ml vial, equivalent to 35 mg/ml

This medication contains 1400 mg of propylene glycol in each 40 ml vial, equivalent to 35 mg/ml

The dose ofPemetrexedTillomedis 500 milligrams per square meter of the surface area of your body. 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 the treatment may be delayed depending on your blood cell count and overall condition.The hospital pharmacist, nurse, or doctor will have dilutedPemetrexedTillomedwith a 5% glucose solution for injection before it is administered to you.

You will always receivePemetrexedTillomedthrough a perfusion (infusion) in one of your veins. The perfusion will last at least 10 minutes.

When usingPemetrexedTillomed 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 a perfusion in one of your veins and is given approximately 30 minutes after the perfusion ofPemetrexedTillomedhas finished. The cisplatin perfusion lasts approximately two hours.

You should normally receive your perfusion 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 withPemetrexedTillomed. 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 that contains folic acid (350 to 1,000 micrograms) and you should take it once a day while takingPemetrexedTillomed. You should take at least five doses during the seven days before the first dose ofPemetrexedTillomed. You should continue taking folic acid for 21 days after the last dose ofPemetrexedTillomed. You will also receive an injection of vitamin B12(1,000 micrograms) the week before administration ofPemetrexedTillomedand approximately every 9 weeks (corresponding to 3 cycles of treatment withPemetrexedTillomed). Vitamin B12and folic acid are given to reduce the possible toxic effects of cancer 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 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 serious and cause death.
• if you start to feelchest pain(frequent) or theheart rate is faster(rare).
• if you havemouth pain, redness, swelling, or sores(very frequent).
• allergic reaction: if you develophives(very frequent),burning or itching sensation(frequent), orfever(frequent). In rare cases, skin reactions can be serious and may cause death. Contact your doctor if you experiencesevere rash,itching, orappearance of blisters(Stevens-Johnson syndrome or toxic epidermal necrolysis).
• if you feelfatiguedordizzy, if you lackbreathingorare pale(because you have fewer hemoglobin than normal, which is very frequent).
• if you experiencebleeding gums, nose, or mouthor anyuncontrolled bleeding, pink or red urine, or unexpected bruises(because you have fewer platelets than normal, which is very frequent).
• if you experience suddendifficulty breathing,intense chest painor coughing up blood in sputum(rare) (may indicate that there is a blood clot in the pulmonary veins).

The side effects ofPemetrexedTillomedmay include:

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

infection• sore throat • low count of neutrophil granulocytes (a type of white blood cell) •low white blood cell count•low hemoglobin levels•mouth pain, redness, swelling, or sores•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 leukocyte)•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• watery eyes• dry conjunctiva (membrane inside the 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 (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• skin itching • skin rash on the body where each lesion resembles a target• hair loss• urticaria• kidney 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)

red blood cell destruction•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 can be fatal)•toxic epidermal necrolysis (a type of severe skin reaction that can be fatal)•autoimmune disorder causing skin rashes 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 scars on the skin•lower limb redness, pain, and swelling•inflammation of the skin and subcutaneous fat (pseudocelulitis)•skin inflammation (dermatitis)•the skin becomes inflamed, itches, reddens, cracks, and becomes rough•intensely itching spots.

Frequency unknown:the frequency cannot be estimated from the available data

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

You may experience some of these side effects 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:www.notificaRAM.es.Medicating the reporting of side effects you can contribute to providing more information on the safety of this medicine.

Keep this medication out 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.

This medication does not require any special storage conditions.

Do not freeze.

Diluted solution for infusion: The medication must be used immediately. When prepared as indicated, the chemical and physical stability of pemetrexed during use was demonstrated for 24 hours at refrigeration temperature. Store protected from light.

This medication is for single use; unused solution must be disposed of according to local regulations.

The active ingredient is pemetrexed.

A vial of 4 ml of concentrate contains 100 mg of pemetrexed (as pemetrexed diarginina)

A vial of 20 ml of concentrate contains 500 mg of pemetrexed (as pemetrexed diarginina)

A vial of 40 ml of concentrate contains 1000 mg of pemetrexed (as pemetrexed diarginina)

The solution contains 25 mg/ml of pemetrexed. Before administration, the healthcare professional must perform another dilution.

The other components areL-Arginina, L-Cisteina, propilenglicol, ácido cítrico and water for injectable preparations.

Appearance of the product and size of the packaging

PemetrexedTillomedis a clear, colorless to slightly yellowish, brown, yellowish-brown or greenish-yellow solution.PemetrexedTillomedis presented in a glass vial.

Each package contains:

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

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

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

The vials are closed with a rubber stopper (bromobutilo), a closure capsule and a flip-top cap.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Laboratorios Tillomed Spain S.L.U.

C/ Cardenal Marcelo Spínola 8, 1st floor, door F

28016 Madrid

Spain

Manufacturer responsible:

Synthon Hispania, S.L.

C/ Castelló 1, Pol. Las Salinas

08830 Sant Boi de Llobregat (Barcelona)

Spain

or

Synthon BV

Microweg 22,

6545 CM Nijmegen

Netherlands

or

Synthon s.r.o.

Brnenská 32/cp. 597,

678 01 Blansko

Republic of Czech

or

STADA Arzneimittel AG,

Stadastraße 2-18,

61118 Bad Vilbel,

Germany

This medicine is authorized in the member states of the European Economic Area with the following names:

Austria:Pemetrexed BioOrganics 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Germany:Pemetrexed BioOrganics 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Spain:Pemetrexed Tillomed 25 mg/ml concentrate for solution for infusion

France:Pemetrexed BioOrganics 25 mg/ml, solution à diluer pour perfusion

Italy:Pemetrexed Synthon

Netherlands:Pemetrexed BioOrganics 25 mg/ml, concentraat voor oplossing voor infusie

Ireland:Pemetrexed 25 mg/ml concentrate for solucion for infusion

United Kingdom:Pemetrexed 25 mg/ml concentrate for solution for infusion

Last review date of this leaflet: December 2024

The detailed and updated information on 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:

Instructions for use, handling and disposal

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

1. Calculate the dose and volume of Pemetrexed Tillomed required. Each vial contains an excess of pemetrexed to facilitate the administration of the nominal required amount. Each vial contains a solution that contains 25 mg/ml of pemetrexed.

1. The appropriate volume of pemetrexed concentrate must be diluted to 100 ml with a 5% glucose solution, without preservatives, and must be administered as an intravenous infusion over 10 minutes.

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

PemetrexedTillomedcontains L-Arginina as an excipient. L-Arginina is incompatible with cisplatin, as it degrades cisplatin. This medicine should not be mixed with other medications. After administration of PemetrexedTillomedthe intravenous lines must be flushed.

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

1. The pemetrexed solutions are for single use. The medication and unused material must be disposed of according to local regulations for cytotoxic agents.

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.The extravasation should be treated according to standard clinical practice with other non-vesicant medications.