PEMETREXED SUN 8.5 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Pemetrexed Sun 5 mg/ml Solution for Infusion

Pemetrexed Sun 6 mg/ml Solution for Infusion

Pemetrexed Sun 6.5 mg/ml Solution for Infusion

Pemetrexed Sun 7 mg/ml Solution for Infusion

Pemetrexed Sun 7.5 mg/ml Solution for Infusion

Pemetrexed Sun 8 mg/ml Solution for Infusion

Pemetrexed Sun 8.5 mg/ml Solution for Infusion

Pemetrexed Sun 9 mg/ml Solution for Infusion

Pemetrexed Sun 10 mg/ml Solution for Infusion

Pemetrexed Sun 11 mg/ml 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 Pemetrexed Sun is and what it is used for
2. What you need to know before you use Pemetrexed Sun
3. How to use Pemetrexed Sun
4. Possible side effects
5. Storage of Pemetrexed Sun
6. Contents of the pack and other information

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

This medicine contains the active substance pemetrexed, which belongs to a group of medicines used to treat cancer. It is used:

• in combination 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.
• in combination with cisplatin, for the initial treatment of patients with advanced lung cancer.
• for the treatment of patients with advanced lung cancer if their disease has responded to treatment or remains unchanged after initial chemotherapy.
• for the treatment of patients with advanced lung cancer whose disease has progressed, and who have already received other initial chemotherapy treatment.

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

Do not use Pemetrexed Sun

• if you are allergic (hypersensitive) to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding, you must discontinue breastfeeding during treatment with Pemetrexed Sun.
• if you have recently received or are going to receive the yellow fever vaccine.

Warnings and Precautions

Consult your doctor or hospital pharmacist before starting to use this medicine

• if you have had or have kidney problems, it may be possible that you cannot receive Pemetrexed Sun.

Before each infusion, you will need to provide blood samples to assess whether your kidney and liver function is sufficient and to assess whether you have enough blood cells to receive Pemetrexed Sun. Your doctor may decide to change your dose or delay treatment depending on your general condition and whether your blood cell count is too low. If you are also receiving cisplatin, your doctor will ensure that 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 with Pemetrexed Sun may occur.
• if you have been vaccinated recently, as this may cause some negative effect with Pemetrexed Sun.
• if you have heart disease or a history of heart disease.
• if you have fluid accumulated around the lung, your doctor may decide to drain the fluid before administering Pemetrexed Sun.

Children and Adolescents

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

Other Medicines and Pemetrexed Sun

Tell your doctor or hospital pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

Please inform your doctor or hospital pharmacist if you are taking

• pain or inflammation medicines (swelling), such as medicines called "non-steroidal 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 Sun infusion and/or the status of your kidney function, your doctor will advise you 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.

Pregnancy, Breastfeeding, and Fertility

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before starting to use this medicine.

During pregnancy, the use of Pemetrexed Sun should be avoided. Your doctor will inform you of the possible risks of using Pemetrexed Sun during pregnancy. Women must use effective contraceptive methods during treatment with Pemetrexed Sun and for 6 months after stopping treatment.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with Pemetrexed Sun, breastfeeding must be discontinued.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with Pemetrexed Sun and must use effective contraceptive methods during and up to 3 months after treatment with this medicine. If you wish to have a child during treatment or in the 6 months following treatment, ask your doctor or pharmacist for advice. Pemetrexed Sun may affect your ability to have children. Talk to your doctor for advice on sperm preservation before starting your treatment.

Driving and Using Machines

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

Pemetrexed Sun contains Sodium

Pemetrexed Sun 5 mg/ml contains 407.9 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 20.4% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 6 mg/ml contains 418.6 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 20.9% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 6.5 mg/ml contains 424.0 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 21.2% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 7 mg/ml contains 429.4 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 21.5% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 7.5 mg/ml contains 434.8 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 21.7% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 8 mg/ml contains 440.1 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 22.0% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 8.5 mg/ml contains 445.5 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 22.3% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 9 mg/ml contains 450.9 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 22.5% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 10 mg/ml contains 461.7 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 23.1% of the maximum recommended daily intake of sodium for an adult.

Pemetrexed Sun 11 mg/ml contains 472.4 mg of sodium (main component of cooking/table salt) per infusion bag. This is equivalent to 23.6% of the maximum recommended daily intake of sodium for an adult.

3. How to use Pemetrexed Sun

The recommended dose of Pemetrexed Sun 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.

You will always receive Pemetrexed Sun through an infusion (drip) in one of your veins. The infusion will last at least 10 minutes.

When using Pemetrexed Sun in combination with cisplatin:

• Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin (75 milligrams per square meter of your body surface area) is also administered through an infusion in one of your veins and is given approximately 30 minutes after the Pemetrexed Sun infusion has finished. The cisplatin infusion lasts approximately two hours.

Normally, you should receive your infusion once every three weeks.

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 Sun. Your doctor gives you this medicine to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.
• Vitamin supplement: your doctor will prescribe oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms) that you must take once a day while taking Pemetrexed Sun. You must take at least five doses during the seven days before the first dose of Pemetrexed Sun. You must continue taking folic acid for 21 days after the last dose of Pemetrexed Sun. Additionally, you will receive a vitamin B12 injection (1,000 micrograms) in the week before administration of Pemetrexed Sun and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Sun). 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, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Inform your doctor immediately if you notice any of the following adverse effects:

• 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 have chest pain (frequent) or your heart rate is faster (infrequent).
• if you have pain, redness, swelling, or sores in the mouth (very frequent).
• allergic reaction: if you develop a skin rash (very frequent) / burning sensation or itching (frequent), or fever (frequent). Rarely, skin reactions can be severe and can cause death. Contact your doctor if you have a severe rash, itching, or appearance of blisters (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• if you experience fatigue, feeling of fainting, develop difficulty breathing, or if you are pale (since you may have less hemoglobin than normal, which is very common).
• if you experience bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (since you may have fewer platelets than normal, which is common).
• if you experience sudden difficulty breathing, severe chest pain, or coughing up blood in your sputum (infrequent) (may indicate a blood clot in the lungs).

Severe adverse effects with Pemetrexed Sun may include

Very frequent (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
• asthenia (fatigue)

Frequent (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 or atrophy (debilitating), mainly in arms and legs
• nerve damage that can cause loss of sensitivity, burning (pain), and unsteady gait
• dizziness
• inflammation or swelling of the conjunctiva (membrane that covers the eyelids and covers 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 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 (condition that affects the pumping ability of the heart muscles)
• irregular heartbeat
• indigestion
• constipation
• abdominal pain
• liver: increased levels of chemicals in the blood produced by the liver
• increased skin pigmentation
• skin itching
• 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
• inflammation and ulceration of the mucous membranes that line the digestive tract

Infrequent (may affect up to 1 in 100 people)

• reduction in the number of red blood cells, white blood cells, and platelets
• ischemia
• ischemia due to blockage of a cerebral artery
• bleeding inside the skull
• 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
• obstruction in one of the pulmonary arteries in the lungs
• inflammation and scarring of the lung mucosa with respiratory problems
• loss of bright red blood through the anus
• bleeding in the gastrointestinal tract
• perforation of the intestine
• inflammation of the esophagus mucosa
• inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)
• inflammation, edema, erythema, and erosion of the mucous membrane surface of the esophagus caused by radiation therapy
• 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 fatal)
• toxic epidermal necrolysis (a type of severe skin reaction that can be fatal)
• autoimmune disorder that causes skin rashes and blisters on the legs, arms, and abdomen
• skin inflammation characterized by the presence of blisters filled with fluid
• skin fragility, blisters, and erosions and scarring on the skin
• redness, pain, and swelling mainly of the lower limbs
• inflammation of the skin and subcutaneous fat (pseudocellulitis)
• skin inflammation (dermatitis)
• the skin becomes inflamed, itchy, red, cracked, and rough
• intensely itchy spots

Frequency not known (cannot be estimated from the available data)

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

You may have some of these symptoms and/or conditions. You should inform your doctor as soon as possible when you start experiencing any of these side effects.

If you are concerned about any of the side effects, talk to your doctor.

Adverse effect reporting

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for human use medicines: https://www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Pemetrexed Sun

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the infusion bag and on the packaging after CAD. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light.

Medicines should not be thrown away through the sewers or in the trash. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

6. Package contents and additional information

Pemetrexed Sun composition

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

The other ingredients are sodium chloride, hydrochloric acid, concentrate (to adjust the pH), sodium hydroxide (to adjust the pH), and water for injectable preparations.

Pemetrexed Sun 5 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 500 mg of pemetrexed.

Pemetrexed Sun 6 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 600 mg of pemetrexed.

Pemetrexed Sun 6.5 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 650 mg of pemetrexed.

Pemetrexed Sun 7 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 700 mg of pemetrexed.

Pemetrexed Sun 7.5 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 750 mg of pemetrexed.

Pemetrexed Sun 8 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 800 mg of pemetrexed.

Pemetrexed Sun 8.5 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 850 mg of pemetrexed.

Pemetrexed Sun 9 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 900 mg of pemetrexed.

Pemetrexed Sun 10 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 1,000 mg of pemetrexed.

Pemetrexed Sun 11 mg/ml solution for infusion: A 100 ml infusion bag contains pemetrexed disodium heptahydrate equivalent to 1,100 mg of pemetrexed.

Product appearance and packaging contents

Pemetrexed Sun solution for infusion is a clear, colorless to yellow or yellow-green solution, free of visible particles.

Pemetrexed Sun solution for infusion is packaged in cardboard boxes, each containing 1 or 5 single-dose infusion bags of 100 ml.

Only some pack sizes may be marketed

Marketing authorization holder

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp Netherlands

Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

Or

Terapia S.A.

124 Fabricii Street

400632, Cluj-Napoca

Cluj County

Romania

You can request more information about this medicine by contacting the local representative of the marketing authorization holder

Sun Pharma Laboratories, S.L.

Rambla de Catalunya 53-55

08007 Barcelona

Spain

Tel: +34 93 342 78 90

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Denmark: Pemetrexed SUN

Finland: Pemetrexed SUN

France: Pemetrexed SUN

Germany: Pemetrexed SUN

Italy: Pemetrexed SUN Pharma

Norway: Pemetrexed SUN

Netherlands: Pemetrexed SUN

Sweden: Pemetrexed SUN

Spain: Pemetrexed Sun

United Kingdom (Northern Ireland): Pemetrexed SUN

Date of the last revision of this prospectus: March 2025

Detailed and updated information on this medicine 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

Handling

• Calculate the dose and decide which size of Pemetrexed Sun infusion bag is needed
• Inspect the product packaging for damage. Do not use if signs of deterioration are observed
• Attach the patient-specific label to the packaging.

Disposal of the infusion bag packaging and inspection of the infusion bag

• For packaging with a window:use the product if the oxygen indicator is pink before opening the packaging to remove the infusion bag; do not use the product if the oxygen indicator is blue before opening the packaging. (The oxygen indicator is present on the aluminum packaging of the infusion bags, which have a transparent window).
• Tear the packaging at the notch. Do not use if the packaging has been previously opened or is damaged.
• Remove the infusion bag from the packaging.
• Use only if the infusion bag and the seal are intact. Before administration, check for small leaks by firmly squeezing the bag for one minute. If leaks exist, discard the bag and the solution as it may not be sterile.
• Parenteral medicines must be visually inspected for particles and discoloration before administration. Do not administer if particles are observed.

Administration

• Break the seal of the stopper by applying pressure with your hand on one side.
• Attach the sterile administration equipment using an aseptic technique.
• Consult the instructions for use that accompany the administration equipment.

Precautions

• Do not use in series connection
• Do not introduce additives into the infusion bag
• The solution for infusion is ready to use and should not be mixed with other medicines.
• Pemetrexed Sun solution for infusion is for single use.

As with any other potentially toxic antineoplastic agent, special care should be taken when handling Pemetrexed Sun solution 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 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 with other non-vesicant drugs.

Disposal

Any unused product should be disposed of in accordance with standard procedures for cytotoxic agents.