PEMETREXED STADAGEN 25 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet:information for the user

Pemetrexed STADAGEN 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, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Pemetrexed Stadagen and what is it used for
2. What you need to know before you use Pemetrexed Stadagen
3. How to use Pemetrexed Stadagen
4. Possible side effects

5 Storage of Pemetrexed Stadagen

1. Contents of the pack and further information

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

Pemetrexed is a medicine used to treat cancer.

Pemetrexed can be given with cisplatin, another anticancer medicine, as a treatment for malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received chemotherapy before.

Pemetrexed can also be given, with cisplatin, as initial treatment for patients with advanced stages of lung cancer.

Pemetrexed may be prescribed for you 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 given for the treatment of patients with advanced stages of lung cancer whose disease has progressed, who have already received other initial chemotherapy treatment.

2. What you need to know before you use Pemetrexed Stadagen

Do not use pemetrexed:

• if you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding, you must stop breastfeeding during treatment with pemetrexed.
• if you have recently been given or are going to be given the yellow fever vaccine.

Warnings and precautions

Talk to your doctor, hospital pharmacist, or nurse before you start using pemetrexed.

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

Before each infusion, you will have to give blood samples to check if your kidney and liver function is sufficient and to check if you have enough blood cells to receive pemetrexed. Your doctor may decide to change 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 make sure you are properly hydrated and 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 an early or late reaction may occur between 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 accumulated around the lung, your doctor may decide to drain the fluid before administering pemetrexed.

Children and adolescents

This medicine must not be given to children and adolescents, as there is no experience with this medicine in children and adolescents under 18 years.

Other medicines and Pemetrexed Stadagen

Tell your doctor if you are taking any other medicine for pain or inflammation (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (NSAIDs), including those bought 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 the status of your kidney function, your doctor will advise which medicines you can use and when you can take them. If you are unsure, consult your doctor or pharmacist to see if 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 take any other medicine.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Pemetrexed should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking pemetrexed during pregnancy. Women must 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.

Breastfeeding should be stopped during treatment with pemetrexed.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with pemetrexed, and therefore, must use effective contraceptive methods during and up to 3 months after treatment with pemetrexed. If you wish to have a child during treatment or in the 3 months following treatment, ask your doctor or pharmacist for advice. Pemetrexed may affect your ability to have children. Consult your doctor for advice on sperm preservation before starting your treatment.

Driving and using machines

Pemetrexed may make you feel tired. Be careful when driving a car or using machines.

Pemetrexed Stadagen contains sodium

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

3. How to use Pemetrexed Stadagen

Dose

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 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 your general 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 given to you.

Method of administration

You will always receive Pemetrexed Stadagen through an infusion into one of your veins. The infusion will last at least 10 minutes.

Duration of use

You should normally receive your infusion 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 given through an infusion into one of your veins and is given approximately 30 minutes after the pemetrexed infusion has finished. The cisplatin infusion lasts approximately two hours.

Additional medication:

Corticosteroids: your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you must take the day before, the day of, and the day after treatment with pemetrexed. Your doctor gives you this medicine to reduce the frequency and severity of skin reactions that you may experience during your cancer treatment.

Vitamin supplement:

• Folic acid: your doctor will prescribe oral folic acid (vitamin) or a multivitamin that contains folic acid (350 to 1,000 micrograms) that you must take once a day while you are 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 during 21 days after the last dose of pemetrexed.
• Vitamin B12: you will also receive a vitamin B12 injection (1,000 micrograms) in the week before pemetrexed is given and then approximately every 9 weeks (corresponding to 3 cycles of treatment with pemetrexed).

Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

You must tell 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 (as you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and life-threatening.
• if you start to feel chest pain (frequent) or your heart rate is faster (uncommon).
• if you have pain, redness, swelling, or sores in the mouth (very frequent).
• allergic reaction: if you develop a rash (very frequent), burning sensation, or itching (frequent) or fever (frequent). In rare cases, skin reactions can be serious and life-threatening. Contact your doctor if you experience 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 are pale (due to having fewer red blood cells than normal, which is very frequent).
• 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 having fewer platelets than normal, which is very frequent).
• if you experience sudden difficulty breathing, severe chest pain, or coughing up blood in your sputum (uncommon) (may indicate that there is a blood clot in the veins of the lungs).

Side effects with pemetrexed may include:

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

• infection
• pharyngitis (sore throat)
• low neutrophil 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
• fatigue (tiredness)

Common (may affect up to 1 in 10 people)

• blood infection
• fever with low neutrophil count (a type of white blood cell)
• low platelet count
• allergic reaction
• loss of body fluids
• altered sense of taste
• nerve damage that can cause muscle weakness and wasting (mainly in arms and legs)
• nerve damage that can cause loss of sensation, burning (pain), and unsteady gait
• dizziness
• inflammation or swelling of the conjunctiva (membrane that covers the eyelids and the white part of the eye)
• dry eyes
• tearful eyes
• dryness of the conjunctiva (membrane inside the eyelids) and the 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 that affects the heart'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
• skin rash that develops in a previously irradiated area
• hair loss
• hives
• kidney failure
• reduced kidney function
• fever
• pain
• excess fluid in the body tissue that causes swelling
• chest pain

Uncommon (may affect up to 1 in 100 people)

• reduction in the number of red blood cells, white blood cells, and platelets
• ischemia
• a type of ischemia caused by blockage of a cerebral artery
• intracranial bleeding
• angina (chest pain caused by reduced blood flow to the heart)
• heart attack
• narrowing or blockage of the coronary arteries
• increased heart rate
• poor distribution of blood to the limbs
• blockage in one of the pulmonary arteries in the lungs
• loss of bright red blood through the anus
• bleeding in the gastrointestinal tract
• perforation of the intestine
• radiation-induced lung inflammation

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 that develops 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 life-threatening)
• toxic epidermal necrolysis (a type of severe skin reaction that can be life-threatening)
• an autoimmune disorder that causes skin rashes and blisters on the legs, arms, and abdomen
• inflammation of the skin characterized by the presence of blisters that are filled with fluid
• fragility of the skin, blisters, and erosions and scarring of the skin
• redness, pain, and swelling mainly of the lower limbs
• skin inflammation (dermatitis)
• the skin becomes inflamed, itchy, red, cracked, and rough
• itchy patches

Not known (frequency cannot be estimated from the available data)

• a type of diabetes derived mainly from kidney disease
• a kidney disorder that involves the death of the epithelial tubular cells that form the renal tubules

You may experience some of these symptoms and/or situations. You should tell your doctor as soon as you start experiencing any of these side effects.

If you are concerned about any side effect, talk to your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pemetrexed Stadagen

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

Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date is the last day of the month shown.

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

Do not freeze

Use immediately after first opening.

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

The solution is clear and may show a range of color from colorless to slightly yellow or yellow-green without affecting the quality of the product.

Do not use if particles are observed.

This medicine is for single use; disposal of unused medicine and all materials that have come into contact with it should be done according to local regulations for cytotoxic medicines.

This medicine is for single use, the unused solution should be discarded according to local requirements for cytotoxic medicines.

6. Container Contents and Additional Information

Composition of Pemetrexed Stadagen

• The active ingredient is pemetrexed.

Each ml 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 of pemetrexed disodium 2.5 hydrate).

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

The other components are mannitol, acetylcysteine, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injectable preparations.

Additional dilution by the healthcare professional is required before administration.

Appearance of Pemetrexed Stadagen and Container Contents

This medicinal product is a concentrate for solution for infusion.

The concentrate solution is clear, 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 flip-off caps.

Each vial is packaged in a transparent PC container with a flip-top PP cap that is tamper-evident and can be reclosed.

Each vial contains 25 mg/ml of pemetrexed.

Each pack contains 1 vial of 4 ml.

Each pack contains 1 vial of 20 ml.

Each pack contains 1 vial of 40 ml.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

info@stada.es

Manufacturer

STADA Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of thisleaflet:April 2025

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

-------------------------------------------------------------------------------------------------------------------------

This information is intended only 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 for solution should be diluted to 100 ml with 0.9 mg/ml (0.9%) sodium chloride injection solution, without preservatives, and administered as an intravenous infusion over 10 minutes.

1. The prepared pemetrexed infusion solution is compatible with administration systems and infusion bags made of polyolefin and polyvinyl chloride. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer's injection and Ringer's injection.

1. Parenteral drugs must be inspected visually for particulate matter or color change prior to administration. If particles are observed, do not administer.

1. The chemical and physical stability 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 should be administered immediately. If not used immediately, the in-use storage time and conditions are the responsibility of the user and normally should not exceed 24 hours at 2°C-8°C, unless the dilution has been prepared in controlled and validated aseptic conditions.

1. Pemetrexed solutions are for single use. The medicinal product and any 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. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be rinsed with plenty of water. Pemetrexed is not a vesicant drug. 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.