PEMETREXED 100 mg Powder

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Pemetrexed Eugia, 100 mg, powder for concentrate for solution for infusion
3. Pemetrexed Eugia, 500 mg, powder for concentrate for solution for infusion
   1. Read all of this leaflet carefully before you start using this medicine because it contains important information for you.
   2. Contents of the pack and other information:
4. What Pemetrexed Eugia is and what it is used for
5. Before you use Pemetrexed Eugia
   1. When you should not use Pemetrexed Eugia
   2. Warnings and precautions
   3. Children and adolescents
   4. Other medicines and Pemetrexed Eugia
   5. Pregnancy
   6. Breastfeeding
   7. Fertility
   8. Driving and using machines
   9. Pemetrexed Eugia contains sodium
6. How to use Pemetrexed Eugia
7. Possible side effects
   1. Reporting of side effects
8. How to store Pemetrexed Eugia
9. Contents of the pack and other information
   1. What Pemetrexed Eugia contains
   2. What Pemetrexed Eugia looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder:
   5. Manufacturer/Importer:
   6. This medicine is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet: 02/2025
   8. The following information is intended for healthcare professionals only:
   9. Storage
   10. Precautions for preparation and administration

Package Leaflet: Information for the User

Pemetrexed Eugia, 100 mg, powder for concentrate for solution for infusion

Pemetrexed Eugia, 500 mg, powder for concentrate for solution for infusion

Pemetrexed

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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

• 1. What Pemetrexed Eugia is and what it is used for
• 2. Before you use Pemetrexed Eugia
• 3. How to use Pemetrexed Eugia
• 4. Possible side effects
• 5. How to store Pemetrexed Eugia
• 6. Contents of the pack and other information

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

Pemetrexed Eugia is used to treat cancer. Pemetrexed Eugia, in combination with another anti-cancer medicine called cisplatin, is used to treat malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received prior chemotherapy. Pemetrexed Eugia, in combination with cisplatin, is used as a first-line treatment for patients with advanced non-small cell lung cancer. Pemetrexed Eugia may be used as a single treatment for patients with advanced non-small cell lung cancer who have already received chemotherapy.

2. Before you use Pemetrexed Eugia

When you should not use Pemetrexed Eugia

• 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 Eugia.
• in patients who have recently been vaccinated or are about to be vaccinated against yellow fever.

Warnings and precautions

Before starting treatment with Pemetrexed Eugia, you should tell your doctor or hospital pharmacist if you have any problems with your kidneys, as you may not be able to receive Pemetrexed Eugia. 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 Pemetrexed Eugia. Your doctor may decide to change your dose or delay your treatment depending on your overall health and blood cell counts. If you are also receiving cisplatin, your doctor will make sure that you are properly hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting. If you have been or are going to be treated with radiation, you should tell your doctor, as you may experience early or late radiation reactions with Pemetrexed Eugia. If you have been recently vaccinated, you should tell your doctor, as you may experience side effects after receiving Pemetrexed Eugia. If you have or have had heart disease, you should tell your doctor. If you have fluid accumulation around the lungs, your doctor may decide to drain the fluid before giving you Pemetrexed Eugia.

Children and adolescents

Pemetrexed Eugia 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.

Other medicines and Pemetrexed Eugia

You should tell your doctor if you are taking any pain or anti-inflammatory medicines (such as non-steroidal anti-inflammatory drugs (NSAIDs), including those that can be bought 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 Pemetrexed Eugia and/or the patient's kidney function, the doctor will advise which medicines can be taken and when. If you are unsure whether your medicines are non-steroidal anti-inflammatory drugs (NSAIDs), you should ask your doctor or pharmacist. You should tell your doctor if you are taking proton pump inhibitors (such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) used to treat heartburn and acid reflux. You should tell your doctor or hospital pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription.

Pregnancy

If you are pregnant or think you may be pregnant, you must tell your doctor. Pemetrexed Eugia should not be used during pregnancy. Your doctor will discuss the potential risks with you. During treatment with Pemetrexed Eugia and for 6 months after the last dose, women must use effective contraception.

Breastfeeding

Women who are breastfeeding should tell their doctor. You must stop breastfeeding during treatment with Pemetrexed Eugia.

Fertility

Men are advised not to father a child during treatment and for 3 months after treatment with Pemetrexed Eugia. Men should use effective contraception during treatment and for 3 months after treatment. If a man wishes to father a child during or after treatment with Pemetrexed Eugia, he should consult his doctor or pharmacist. Pemetrexed Eugia may affect fertility. Before starting treatment, patients may seek advice on sperm conservation.

Driving and using machines

Pemetrexed Eugia may cause fatigue. You should be careful when driving or using machines.

Pemetrexed Eugia contains sodium

Pemetrexed Eugia, 100 mg, powder for concentrate for solution for infusion This medicine contains less than 1 mmol (23 mg) of sodium per vial, which is essentially sodium-free. Pemetrexed Eugia, 500 mg, powder for concentrate for solution for infusion This medicine contains 54 mg of sodium (the main ingredient of common salt) per vial, which is 2.7% of the maximum recommended daily intake of sodium for adults.

3. How to use Pemetrexed Eugia

The dose of Pemetrexed Eugia is 500 milligrams per square meter of body surface area. The dose is calculated based on the patient's height and weight. The dose may be adjusted or treatment delayed depending on blood cell counts and the patient's overall health. Before administration, the hospital pharmacist, nurse, or doctor will dissolve the powder in 9 mg/ml (0.9%) sodium chloride injection solution. Pemetrexed Eugia is always given as an infusion into a vein. The infusion takes about 10 minutes. When used in combination with cisplatin: The doctor or hospital pharmacist will calculate the dose based on the patient's height and weight. Cisplatin is also given as an intravenous infusion and is administered about 30 minutes after the end of the Pemetrexed Eugia infusion. The cisplatin infusion takes about 2 hours. The infusion is usually given once every 3 weeks. Additional medicines: Corticosteroids: The doctor will prescribe steroids in tablet form (equivalent to 4 milligrams of dexamethasone twice a day) to be taken the day before, the day of, and the day after treatment with Pemetrexed Eugia. These medicines are used to reduce the frequency and severity of skin reactions that may occur during cancer treatment. Vitamin supplements: The doctor will prescribe folic acid (vitamin) or a multivitamin supplement containing folic acid (350 to 1000 micrograms) to be taken once a day during treatment with Pemetrexed Eugia. For 7 days before the first dose of Pemetrexed Eugia, you should take at least 5 doses of folic acid. You should continue taking folic acid for 21 days after the last dose of Pemetrexed Eugia. During the week before treatment with Pemetrexed Eugia and then every 9 weeks (which corresponds to 3 cycles of chemotherapy with Pemetrexed Eugia), you will also receive vitamin B12 (1000 micrograms) by injection. The administration of vitamin B12 and folic acid is intended to reduce the possible side effects of cancer treatment. If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Pemetrexed Eugia can cause side effects, although not everybody gets them. If you experience any of the following symptoms, you should contact your doctor immediately:

• Fever or infection (very common or common): if you have a fever of 38°C or higher, sweating, or other signs of infection (due to the possibility of a low white blood cell count, which is very common). Infection (sepsis) can be severe and life-threatening.
• If you experience chest pain (common) or a rapid heartbeat (uncommon).
• If you experience pain, redness, swelling, or ulcers in the mouth (very common).
• Allergic reaction: if you experience a skin rash (very common), a burning or stinging sensation (common), or fever (common). Rarely, skin reactions can be severe and life-threatening. You should contact your doctor if you experience a severe rash, itching, or blisters (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you experience fatigue, fainting, shortness of breath, or pale skin (due to the possibility of a low red blood cell count, which is very common).
• If you experience bleeding from the gums, nose, or mouth, or any bleeding that cannot be stopped, red or pink urine, or unexpected bruising (due to the possibility of a low platelet count, which is common).
• If you experience sudden shortness of breath, severe chest pain, or coughing up blood (uncommon) (which may indicate a blood clot in the lungs).

Pemetrexed Eugia may cause 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 level
• Pain, redness, swelling, or ulcers in the mouth
• Loss of appetite
• Nausea
• Vomiting
• Diarrhea
• Skin rash
• Peeling skin
• Abnormal blood test results indicating kidney problems
• Fatigue (tiredness)

Common(may affect up to 1 in 10 people):

• Blood infection
• Fever with a low neutrophil count (a type of white blood cell)
• Low platelet count
• Allergic reaction
• Dehydration
• Taste disturbances
• Nerve damage that can cause weakness and wasting of muscles, mainly in the arms and legs
• Nerve damage that can cause loss of sensation, burning pain, and unsteady gait
• Dizziness
• Inflammation or swelling of the conjunctiva (the membrane covering the white part of the eyes 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)
• Swelling of the eyelids
• Eyelid problems with dryness, tearing, irritation, and (or) pain
• Heart failure (a condition in which the heart does not pump blood properly)
• Abnormal heart rhythm
• Constipation
• Abdominal pain
• Liver problems, with increased levels of liver enzymes in the blood
• Increased skin pigmentation
• Itching
• Ring-shaped skin rash
• Hair loss
• Hives
• Kidney failure
• Kidney problems
• Fever
• Pain
• Excessive fluid accumulation in the body, causing swelling
• Chest pain
• Inflammation and ulcers of the mucous membranes lining the digestive tract

Uncommon(may affect up to 1 in 100 people):

• Low red blood cell, white blood cell, and platelet count
• Stroke
• A type of stroke in which a blood vessel in the brain becomes blocked
• Bleeding in the brain
• Angina (chest pain caused by reduced blood flow to the heart)

Rare(may affect up to 1 in 1,000 people):

• Breakdown of red blood cells
• Anaphylactic shock (a severe allergic reaction)
• Liver inflammation
• Redness of the skin
• Skin rash that appears in areas previously exposed to radiation

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

• Infections of the skin and soft tissues
• 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 on the skin of the legs, arms, and abdomen
• Blistering skin condition
• Brittle skin, with blisters, ulcers, and scarring
• Redness, pain, and swelling, mainly of the lower limbs
• Inflammation of the skin and subcutaneous tissue (pseudoscleroderma)
• Skin inflammation
• Inflammation, itching, redness, cracking, and roughness of the skin
• Severe itching

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

• A type of diabetes caused by kidney problems
• Kidney problems, resulting in the death of kidney cells

Any of these symptoms can occur. You should contact your doctor as soon as possible if you experience any of these side effects. You should tell your doctor if you are concerned about any of these symptoms.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. By reporting side effects, you can help provide more information on the safety of this medicine. Side effects can also be reported to the marketing authorization holder.

5. How to store Pemetrexed Eugia

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 carton and vials after EXP. The expiry date refers to the last day of that month.

100 mg:Store below 30°C.

500 mg:No special storage precautions are required.

Reconstituted and diluted infusion solution: The chemical and physical stability of the reconstituted and diluted solution for infusion has been demonstrated for 24 hours at 2°C - 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C, unless reconstitution/dilution has been carried out in controlled and validated aseptic conditions.

Do not use this medicine if you notice signs of deterioration. This medicine is for single use only. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Pemetrexed Eugia contains

The active substance is pemetrexed. Pemetrexed Eugia, 100 mg: each vial contains 100 milligrams of pemetrexed (as pemetrexed disodium 2.5 hydrate). Pemetrexed Eugia, 500 mg: each vial contains 500 milligrams of pemetrexed (as pemetrexed disodium 2.5 hydrate). The reconstituted solution contains 25 mg/ml of pemetrexed. Further dilution by a healthcare professional is required before administration. The other ingredients are mannitol, hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment).

What Pemetrexed Eugia looks like and contents of the pack

Powder for concentrate for solution for infusion. Lyophilized cake or powder, white to light yellow or greenish-yellow in color. The medicine is available in packs of 1 vial. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Eugia Pharma (Malta) Ltd.

Vault 14, level 2

Valletta Waterfront

Floriana, FRN1914

Malta

e-mail: [email protected]

Manufacturer/Importer:

APL Swift Services (Malta) Ltd.

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

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

Belgium:

Pemetrexed Eugia 500 mg/ 1000 mg poeder voor concentraat voor oplossing voor infusie/ poudre pour solution à diluer pour perfusion / Pulver für ein Konzentrat zur Herstellung einer Infusionslösung

Denmark:

Pemetrexed Aurobindo

France:

PEMETREXED ARROW 100 mg/ 500 mg/ 1000 mg poudre pour solution à diluer pour perfusion

Germany:

Pemetrexed PUREN 100 mg/ 500 mg/ 1000 mg Pulver zur Herstellung eines Konzentrates zur Herstellung einer Infusionslösung

Italy:

Pemetrexed Aurobindo

Poland:

Pemetrexed Eugia

Portugal:

Pemetrexedo Eugia

Date of last revision of the leaflet: 02/2025

The following information is intended for healthcare professionals only:

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

• 1. Preparation of pemetrexed solution and further dilution of the infusion solution should be carried out under aseptic conditions.
• 2. The dose should be calculated and the number of vials of Pemetrexed Eugia required should be determined. Each vial contains an overfill of pemetrexed to facilitate delivery of the labeled amount.
• 3. Pemetrexed Eugia, 100 mg: The contents of each 100 mg vial should be reconstituted with 4.2 ml of 9 mg/ml (0.9%) sodium chloride injection solution without preservatives. The resulting solution contains 25 mg/ml of pemetrexed.

Pemetrexed Eugia, 500 mg: The contents of each 500 mg vial should be reconstituted with 20 ml of 9 mg/ml (0.9%) sodium chloride injection solution without preservatives. The resulting solution contains 25 mg/ml of pemetrexed. Each vial should be gently rotated until the powder is completely dissolved. The reconstituted solution is clear and ranges in color from colorless to yellow or yellowish-green, without any adverse effect on the quality of the product. The pH of the reconstituted solution ranges from 6.6 to 7.8. Further dilution is required.

• 4. The appropriate volume of the reconstituted pemetrexed solution should be further diluted to 100 ml with 9 mg/ml (0.9%) sodium chloride injection solution without preservatives, and administered as an intravenous infusion over 10 minutes.
• 5. Pemetrexed infusion solutions prepared as directed are compatible with infusion sets and bags made of polyvinyl chloride (PVC) with polyolefin, and polypropylene. Pemetrexed is incompatible with diluents containing calcium, including Ringer's solution and lactated Ringer's solution.
• 6. Before administration, the solution should be inspected for particulate matter and discoloration. If particulate matter is present, the solution should not be administered.
• 7. Pemetrexed solutions are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

Storage

The chemical and physical stability of the reconstituted and diluted solution for infusion has been demonstrated for 24 hours at 2°C - 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C, unless reconstitution/dilution has been carried out in controlled and validated aseptic conditions.

Precautions for preparation and administration

As with other potentially toxic anticancer agents, caution should be exercised when handling and preparing Pemetrexed Eugia solutions for infusion. It is recommended that gloves are worn. If pemetrexed solution comes into contact with the skin, the area should be washed immediately and thoroughly with soap and water. If pemetrexed solution comes into contact with the mucous membranes, the area should be flushed with water. Pemetrexed is not a vesicant. There is no specific antidote for extravasation of pemetrexed. A few cases of extravasation of pemetrexed have been reported, but these were not assessed by investigators as serious. If extravasation occurs, the standard management of extravasation should be followed, as with other non-vesicant drugs.