Pemetreksed Sun

1. What Pemetreksed SUN is and what it is used for

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

• in combination with another anticancer medicine cisplatin for the treatment of malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received prior chemotherapy;
• in combination with cisplatin as a first-line treatment for patients with advanced non-small cell lung cancer;
• for patients with advanced non-small cell lung cancer who have received prior chemotherapy;
• for the treatment of patients with advanced non-small cell lung cancer who have progressed after prior chemotherapy.

2. What you need to know before you use Pemetreksed SUN

Contraindications

• 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 Pemetreksed SUN;
• if you have recently received or are going to receive a yellow fever vaccine.

NL/H/3289/001-003/IA/011

Warnings and precautions

Before starting treatment with Pemetreksed SUN, you should discuss with your doctor or pharmacist:

• if you have or have had kidney problems, as Pemetreksed SUN may not be suitable for you. Before each infusion, your doctor will take blood samples to check that your liver and kidneys are working properly and that you have enough blood cells to receive Pemetreksed SUN. Depending on your overall health and in case of a significant decrease in blood cell count, your doctor may adjust the dose or delay the administration of Pemetreksed SUN. If you are also being treated with cisplatin, your doctor will check your hydration status and advise you on appropriate treatment to prevent vomiting.
• if you have received or are going to receive radiation therapy, as you may have an early or late radiation reaction with Pemetreksed SUN;
• if you have recently received a vaccine, as it may cause side effects in combination with Pemetreksed SUN;
• if you have or have had heart disease;
• if you have fluid accumulation around the lungs, your doctor may decide to perform a procedure to remove the fluid before administering Pemetreksed SUN.

Children and adolescents

Pemetreksed SUN should not be used in children and adolescents under 18 years of age, as there is no experience with the use of this medicine in this age group.

Pemetreksed SUN and other medicines

Tell your doctor or pharmacist about all the medicines you are taking or have recently taken, as well as any medicines you plan to take. Inform your doctor or pharmacist if you are taking:

• medicines for pain and inflammation (e.g., anti-inflammatory drugs), such as non-steroidal anti-inflammatory drugs (NSAIDs), including those available without a prescription (e.g., ibuprofen). There are many types of non-steroidal anti-inflammatory drugs (NSAIDs) with different durations of action. Depending on the planned date of administration of Pemetreksed SUN and the patient's kidney function, the doctor will provide information on which medicines can be taken and when. In case of doubt about whether the medicines being taken belong to the group of non-steroidal anti-inflammatory drugs (NSAIDs), you should ask your doctor or pharmacist.

Tell your doctor if you are taking medicines called proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) used to treat heartburn and acid reflux.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. You should avoid taking Pemetreksed SUN during pregnancy. Your doctor will inform you about the potential risks associated with taking Pemetreksed SUN during pregnancy. During treatment with Pemetreksed SUN and for 6 months after the last dose, women must use effective contraception.

Breastfeeding

Women who are breastfeeding should inform their doctor. During treatment with Pemetreksed SUN, breastfeeding should be discontinued.

Fertility

It is recommended that men do not try to father a child during treatment and for 3 months after the last dose of Pemetreksed SUN and use effective contraception during this time. If a man wants to try to father a child during treatment with Pemetreksed SUN or within 3 months after the last dose, he should consult his doctor or pharmacist. Pemetreksed SUN may affect fertility. Before starting treatment, you should discuss with your doctor about sperm preservation.

Driving and using machines

Pemetreksed SUN may cause fatigue. You should be cautious when driving or operating machinery.

Pemetreksed SUN contains sodium

Pemetreksed SUN 100 mg contains less than 1 mmol (23 mg) of sodium per vial, which means that the medicine is essentially "sodium-free". Pemetreksed SUN 500 mg contains approximately 54 mg of sodium (the main component of common salt) per vial, which corresponds to 2.7% of the maximum recommended daily intake of sodium in the diet for adults. Pemetreksed SUN 1000 mg contains approximately 108 mg of sodium (the main component of common salt) per vial, which corresponds to 5.4% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Pemetreksed SUN

The recommended dose of Pemetreksed SUN is 500 milligrams per square meter of body surface area. The body surface area is calculated based on the patient's height and weight. The dose is adjusted according to the body surface area. The dose may be adjusted or delayed based on the results of blood tests and the patient's overall health. Before administering Pemetreksed SUN, the pharmacist, nurse, or doctor will dissolve the powder in 9 mg/ml (0.9%) sodium chloride injection solution. Pemetreksed SUN is always administered as an intravenous infusion. The infusion lasts about 10 minutes. Administration of Pemetreksed SUN in combination with cisplatin:

• the doctor or pharmacist will calculate the dose based on the patient's height and weight. Cisplatin is also administered as an intravenous infusion. The cisplatin infusion is started about 30 minutes after the end of the Pemetreksed SUN administration and lasts about two hours.

The medicine will usually be administered every 3 weeks. Additional medicines:

• corticosteroids: the doctor will prescribe steroids in tablets (equivalent to 4 milligrams of dexamethasone twice a day), which should be taken the day before, the day of, and the day after Pemetreksed SUN administration. These medicines are used to reduce the frequency and severity of skin reactions that may occur during anticancer treatment.
• vitamins: the doctor will prescribe folic acid (vitamin) or a multivitamin product containing folic acid (350-1000 micrograms), which should be taken orally once a day during treatment with Pemetreksed SUN. During the 7 days preceding the first dose of Pemetreksed SUN, you should take at least 5 doses of folic acid. You should continue taking folic acid for 21 days after the last dose of Pemetreksed SUN. Every 9 weeks (corresponding to 3 cycles of chemotherapy with Pemetreksed SUN), patients will also receive vitamin B12 (1000 micrograms) injections. The administration of vitamin B12 and folic acid is intended to reduce the risk of side effects of anticancer medicines. In case of doubt, you should consult your doctor, pharmacist, or nurse.

NL/H/3289/001-003/IA/011

4. Possible side effects

Like all medicines, Pemetreksed SUN can cause side effects, although not everybody gets them.

Severe side effects

Tell your doctor immediately if you experience any of the following severe side effects:

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

• pain, redness, swelling, or ulcers in the mouth
• allergic reaction: skin rash. In rare cases, skin reactions can be severe and life-threatening.
• low hemoglobin levels (anemia). You may feel tired, weak, short of breath, or pale.

Common (may affect up to 1 in 10 people)

• fever or infection: if you have a fever of 38°C or higher, excessive sweating, or other signs of infection (due to the possibility of a significant decrease in white blood cell count, which is a very common side effect). Infection (sepsis) can be severe and life-threatening.
• chest pain
• allergic reaction: burning or tingling sensation and fever
• low platelet count. You may experience bleeding from the gums, nose, or mouth, or other bleeding that cannot be stopped, red or pink urine, or unexpected bruising on the skin.

Uncommon (may affect up to 1 in 100 people)

• rapid heartbeat
• blood clots in the blood vessels of the lungs (pulmonary embolism). You may experience sudden shortness of breath, severe chest pain, or coughing up blood.

Rare (may affect up to 1 in 1000 people)

• allergic reaction: severe rash, itching, or blisters (symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis).

Other side effects

Tell your doctor as soon as possible if you experience any of the following side effects:

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 ulcers in the mouth
• loss of appetite
• vomiting
• diarrhea
• nausea
• skin rash
• skin peeling
• abnormal blood test results indicating impaired kidney function
• fatigue

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
• fluid loss
• taste disorders
• nerve damage causing weakness and muscle wasting in the arms and legs
• nerve damage causing loss of sensation, burning pain, and unsteady gait
• dizziness
• inflammation or swelling of the conjunctiva (the membrane covering the white part of the eye and the inside of the eyelids)
• dry eyes
• excessive tearing
• dryness of the conjunctiva and cornea (the clear layer covering the front of the eye and the pupil)
• swelling of the eyelids
• eye disorders with dryness, tearing, irritation, and/or pain
• heart failure (a condition that affects the heart's ability to pump blood)
• irregular heartbeat
• indigestion
• constipation
• abdominal pain
• liver: increased levels of liver enzymes in the blood
• increased skin pigmentation
• itching
• skin rash with target-like lesions
• hair loss
• hives
• kidney failure
• impaired kidney function
• fever
• pain
• excessive fluid in the body tissues causing swelling
• chest pain
• inflammation and ulceration of the mucous membranes lining the digestive tract

Uncommon (may affect up to 1 in 100 people)

• decrease in red blood cell, white blood cell, and platelet count
• stroke
• a type of stroke where a blood vessel in the brain becomes blocked
• bleeding in the brain
• angina (chest pain caused by reduced blood flow to the heart)
• heart attack
• narrowing or blockage of the coronary arteries
• rapid heartbeat
• poor blood flow to the limbs
• blockage of a pulmonary artery
• inflammation and scarring of the membrane surrounding the lungs, with breathing difficulties
• bright red bleeding from the anus
• bleeding from the digestive tract
• rupture of the intestinal wall
• inflammation of the esophagus
• inflammation of the colon, which may be accompanied by bleeding from the intestines and anus (observed only in combination with cisplatin)

NL/H/3289/001-003/IA/011

• inflammation, swelling, redness, and ulcers of the esophagus caused by radiation therapy
• radiation-induced pneumonia

Rare (may affect up to 1 in 1000 people)

• breakdown of red blood cells
• anaphylactic shock (a severe allergic reaction)
• inflammation of the liver
• redness of the skin
• skin rash developing in areas previously exposed to radiation

Very rare (may affect up to 1 in 10,000 people)

• skin and soft tissue infections
• Stevens-Johnson syndrome (a severe skin and mucous membrane reaction that can be life-threatening)
• toxic epidermal necrolysis (a severe skin reaction that can be life-threatening)
• autoimmune disorders, resulting in skin rash and blistering lesions on the skin of the legs, arms, and abdomen
• skin inflammation characterized by the presence of fluid-filled blisters
• skin fragility, blisters, ulcers, and scarring
• redness, pain, and swelling, mainly of the lower limbs
• inflammation of the skin and subcutaneous fatty tissue
• skin inflammation
• inflammation, itching, redness, cracking, and dryness of the skin
• severe itching skin lesions

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

• a type of diabetes caused by kidney problems
• kidney damage, resulting in the death of kidney tubule cells.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist. You can also report side effects directly to the Department of Adverse Reaction Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl. You can also report side effects to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pemetreksed SUN

Your doctor, pharmacist, or nurse knows how to store Pemetreksed SUN. Store the medicine out of sight and reach of children. Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month stated. There are no special precautions for storage. The medicine should be used immediately after opening the vial to avoid microbial contamination. If the medicine is not used immediately after opening, the responsibility for the correct storage time and conditions lies with the person administering the medicine, which should not exceed 24 hours at a temperature of 2°C - 8°C, unless the preparation of the solution was done under controlled and validated aseptic conditions. Before administration, the medicine stored in the refrigerator should be allowed to reach room temperature.

6. Contents of the pack and other information

What Pemetreksed SUN contains

• The active substance is pemetrexed. Each vial contains 100 mg, 500 mg, or 1000 mg of pemetrexed (as pemetrexed disodium heptahydrate). The reconstituted solution contains 25 mg/ml of pemetrexed. Before administration, the medicine must be further diluted. This will be done by a healthcare professional.
• The other ingredients are: mannitol, hydrochloric acid, and/or sodium hydroxide (for pH adjustment) (see section 2 for more information).

What Pemetreksed SUN looks like and contents of the pack

Pemetreksed SUN is a powder for concentrate for solution for infusion in a vial. It is a lyophilized powder that is white to light yellow or greenish-yellow in color. Each pack contains one vial.

Marketing authorization holder

Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp Netherlands

Manufacturer/Importer

Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp Netherlands

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

Germany: Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung Italy: Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg polvere per concentrato per soluzione per infusione Netherlands: Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg poeder voor concentraat voor oplossing voor infusie Poland: Pemetreksed SUN Romania: Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg pulbere pentru concentrat pentru soluţie perfuzabilă Spain: Pemetrexed SUN 100 mg polvo para concentrado para solución para perfusión EFG Pemetrexed SUN 500 mg polvo para concentrado para solución para perfusión EFG Pemetrexed SUN 1000 mg polvo para concentrado para solución para perfusión United Kingdom (Northern Ireland): Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg powder for concentrate for solution for infusion Date of last revision of the leaflet:03.02.2025 NL/H/3289/001-003/IA/011

The following information is intended for healthcare professionals only

Instructions for preparation, administration, and disposal of the medicine.

• 1. Preparation of the pemetrexed solution and further dilution of the infusion solution should be performed under aseptic conditions.
• 2. Calculate the dose and the number of Pemetreksed SUN vials needed. Each vial contains a little more medicine than stated on the label, which makes it easier to withdraw the volume stated on the label.
• 3. Pemetreksed SUN 100 mg: Dissolve the contents of the 100 mg vial in 4.2 ml of sodium chloride 9 mg/ml (0.9%) injection solution, which does not contain preservatives. The resulting solution contains 25 mg/ml of pemetrexed.

Pemetreksed SUN 500 mg: Dissolve the contents of the 500 mg vial in 20 ml of sodium chloride 9 mg/ml (0.9%) injection solution, which does not contain preservatives. The resulting solution contains 25 mg/ml of pemetrexed. Pemetreksed SUN 1000 mg: Dissolve the contents of the 1000 mg vial in 40 ml of sodium chloride 9 mg/ml (0.9%) injection solution, which does not contain preservatives. The resulting solution contains 25 mg/ml of pemetrexed. Each vial should be gently rotated until the powder is completely dissolved. The prepared solution is clear, colorless to yellow or yellow-green (the color does not affect the quality of the product). The pH of the prepared solution is between 6.6 and 7.8. The osmolality of the solution is between 480 and 570 mOsm/kg. The solution must be further diluted.

• 4. The appropriate volume of the prepared pemetrexed solution should be further diluted to a volume of 100 ml using sodium chloride 9 mg/ml (0.9%) injection solution, which does not contain preservatives. The medicine should be administered as an intravenous infusion over 10 minutes.
• 5. Pemetrexed solutions for infusion prepared as described above do not show incompatibility with infusion bags and administration sets with an inner layer made of polyvinyl chloride and polyolefin. Pemetrexed shows physical incompatibility with diluents containing calcium, including Ringer's injection with lactates and Ringer's injection.
• 6. Before parenteral administration, the solution should be inspected for visible particles and changes in color. If the solution contains visible particles, the medicine should not be administered.
• 7. The pemetrexed solution is for single use only. Any unused product or waste material should be disposed of in accordance with local regulations for cytotoxic medicines.

Precautions when handling and administering the medicine.

As with other potentially toxic anticancer medicines, caution should be exercised when handling Pemetreksed SUN and preparing solutions for infusion. Gloves should be worn. In case of skin contact with the pemetrexed solution, the skin should be washed immediately and thoroughly with soap and water. In case of contact with the mucous membranes, the area should be rinsed thoroughly with water. Pemetreksed does not cause blistering. There is no specific antidote in case of extravasation. There have been reports of a few cases of extravasation, which were not considered serious by the investigators. In case of extravasation, standard practice for non-vesicant substances should be followed.