Label:information for the user

Pemetrexed STADAGEN 25 mg/ml concentrate for solution for infusion

Read this label carefully before starting to use this medicine,because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects,consult your doctor, pharmacist, or nurse, eveniftheyare not listed in this label. See section 4.

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

2.What you need to knowbeforestarting touse Pemetrexed Stadagen

3.How to use Pemetrexed Stadagen

4.Possible adverse effects

5Storage of Pemetrexed Stadagen

6.Contents of the package and additional information

Pemetrexed is a medication used for the treatment of cancer.

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

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

Pemetrexed may be prescribed if you have advanced-stage 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, who have already received initial chemotherapy treatment.

No use pemetrexed:

• if you are allergic to pemetrexed or any of the other components of this medication (listed in section 6).
• if you are breastfeeding, you should 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, hospital pharmacist, or nurse before starting to use pemetrexed.

If you have or have had kidney problems, tell your doctor or hospital pharmacist as it may be possible that you cannot receive pemetrexed.

Before each infusion, you will need to give 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 depending 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 will receive the appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are to receive radiation therapy, please consult with your doctor, as there may be an early or late reaction between the radiation and pemetrexed.

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

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

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

Children and adolescents

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

Other medications and Pemetrexed Stadagen

Inform your doctor if you are taking any other medication for pain or inflammation (swelling), such as nonsteroidal anti-inflammatory drugs (NSAIDs), including those obtained 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 taking, have recently taken, or may need to take any other medication.

Pregnancy,breastfeedingand fertility

Pregnancy

If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.During pregnancy, the use of pemetrexed should be avoided. Your doctor will inform you of the possible risks of taking 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 seek advice on sperm conservation before starting your treatment.

Driving and operating machinery

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

Pemetrexed Stadagen contains sodium

This medication contains 110.03 mg of sodium (main component of table salt/for cooking) in each 500 mg dose of pemetrexed per square meter of body surface area. This is equivalent to 5.51% of the maximum daily sodium intake recommended for an adult.

Dose

The dose of pemetrexed is 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 treatment may be delayed depending on your blood cell count and overall condition.

The hospital pharmacist, nurse, or doctor will have diluted Pemetrexed Stadagen with 9 mg/ml (0.9%) sodium chloride solution for injection before it is administered to you.

Administration form

You will always receive Pemetrexed Stadagen through a drip in one of your veins. The drip will last at least 10 minutes.

Duration of use

You should normally receive your drip once every three weeks.

When using pemetrexed 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 you have finished the pemetrexed drip. The cisplatin drip lasts approximately two hours.

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. Your doctor gives you this medication to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.

Vitamin supplement:

• Folic acid: your doctor will prescribe you oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms) that you must take once a day while receiving pemetrexed. You must take at least five doses during the seven days before the first dose of pemetrexed. You must continue taking folic acid for 21 days after the last dose of pemetrexed.
• Vitamin B12: in addition, you will 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 B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

If you have any other questions about the use of this medication, 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 (respectively, frequent or very frequent): 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 feel chest pain (frequent) or your heart rate is faster (rare).
• if you have pain, redness, swelling, or sores in your mouth (very frequent).
• allergic reaction: if you develop hives (very frequent), burning sensation, or itching (frequent) or fever (frequent). In rare cases, skin reactions can be severe and may cause death. Contact your doctor if you present severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• if you feel tired or dizzy, if you lack breath or are pale (since you have fewer hemoglobin than normal, which is very frequent).
• if you experience bleeding gums, nose, or mouth or any bleeding that does not stop, pink or red urine, or unexpected bruises (since you have fewer platelets than normal, which is very frequent).
• if you experience sudden difficulty breathing, intense chest pain, or coughing up blood in your sputum (rare) (which may indicate that there is a blood clot in the veins of the lungs).

The side effects of pemetrexed may include:

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

• infection
• pharyngitis (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
• blood test abnormalities showing reduced kidney function
• asthenia (fatigue)

Frequent (may affect up to 1 in 10 people)

• blood infection
• fever with low count of neutrophil granulocytes (a type of white blood cell)
• low platelet count
• allergic reaction
• fluid loss
• alterations in taste
• motor nerve damage that may cause muscle weakness and atrophy (emaciation mainly in arms and legs)
• sensory nerve damage that may 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 eye
• tearful eyes
• dryness of the conjunctiva (inner membrane of the eyelids and covers 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 pigmentation increase
• skin itching
• 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 internally

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 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
• redness, pain, and swelling mainly of 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

Unknown (frequency cannot be estimated from available data)

• a type of diabetes mainly caused by kidney disease
• renal disorder involving the death of tubular epithelial cells forming 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 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 onthe labeledafter CAD. The expiration date is the last day of the month indicated.

Store the closed vial in the refrigerator (2°C – 8°C)

Do not freeze

After the first opening, use immediately.

Infusion solution: the medication must be used immediately. Once prepared as indicated, the chemical and physical stability of pemetrexed in use was demonstrated for 72 hours at refrigeration temperature (2°C – 8°C).

The solution is transparent and may show a range of color from colorless to slightly yellow or yellow-green without indicating that the product quality has been affected.

Do not use if particles are observed.

This medication is for single use; the disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic medications.

This medication is for single use, unused solution must be disposed of in accordance with local requirements for cytotoxic medications.

Pemetrexed Stadagen Composition

• The active ingredient is pemetrexed.

Each milliliter of concentrate for solution for infusion contains 25 mg of pemetrexed (as 30.21 mg of pemetrexed disodium hemipentahydrate).

A vial with 4 ml of concentrate contains 100 mg of pemetrexed (as 120.83 mg of pemetrexed disodium 2.5 hydrate).

A vial with 20 ml of concentrate contains 500 mg of pemetrexed (as 604.13 mg pemetrexed disodium 2.5 hydrate).

A vial with 40 ml of concentrate contains 1,000 mg of pemetrexed (as 1,208.26 mg pemetrexed disodium 2.5 hydrate).

The other components are mannitol, acetylcysteine, sodium hydroxide (to adjust the pH), hydrochloric acid (to adjust the pH), and water for injection preparations.

A further dilution by the healthcare professional is required before administration.

Appearance of Pemetrexed Stadagen and packaging content

This medicine is a concentrate for solution for infusion.

The concentrate solution is transparent, colorless or slightly yellow or yellow-green. It is packaged in transparent glass vials sealed with a chlorobutyl/butyl rubber stopper coated with fluoropolymer Type I and aluminum pressure caps.

Each vial is packaged in a transparent PC container with a PP hinged lid that can be re-closed.

Each vial contains 25 mg/ml of pemetrexed.

Each package contains 1 vial of 4 ml.

Each package contains 1 vial of 20 ml.

Each package contains 1 vial of 40 ml.

Only some package sizes may be marketed.

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder

STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Responsible Manufacturer

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:

Last review date of thisleaflet:April 2025

The detailed 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 administration by intravenous infusion.

1. Calculate the dose and the number of vials of pemetrexed required. Each vial contains an excess of pemetrexed to facilitate the supply of the amount indicated on the label.

1. The appropriate volume of the pemetrexed concentrate solution should be diluted to 100ml with0.9 mg/ml (0.9%) sodium chloride injection, without preservatives,and administered as an intravenous infusion over 10minutes.

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

1. Parenteral medicines must be visually inspected to detect the presence of particles or changes in color before administration. If particles are observed, do not administer.

1. The chemical and physical stability in use of the infusion solution has been demonstrated for 72 hours at a temperature between 2°C and 8°C. From a microbiological point of view, the infusion solution must be administered immediately. If not used immediately, the time and conditions of use are the responsibility of the user and should not normally exceed 24 hours at 2°C-8°C, unless the dilution has been prepared in controlled and validated aseptic conditions.

1. The pemetrexed solutions are for single use. The medicine and unused material should be disposed of in accordance with 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 infusion solutions. 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 plenty of water. Pemetrexed is not a vesicant. 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 as with other non-vesicant drugs.