Pemetrexed eugia

Package leaflet: Information for the user

Pemetrexed Eugia, 100 mg, powder for concentrate for infusion solution
Pemetrexed Eugia, 500 mg, powder for concentrate for infusion solution
Pemetrexedum
Please read all of this leaflet carefully before this medicine is administered, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

1. What Pemetrexed Eugia is and what it is used for
2. Important information before receiving 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 a medicine used in the treatment of malignant tumours.
Pemetrexed Eugia, in combination with another anticancer medicine, cisplatin, is used in the treatment of malignant pleural mesothelioma, a type of cancer affecting the lining of the lung, in patients who have not previously received chemotherapy.
Pemetrexed Eugia in combination with cisplatin is used as initial treatment in patients with advanced non-squamous non-small cell lung cancer.
Pemetrexed Eugia may be prescribed to patients with advanced non-squamous non-small cell lung cancer who have responded to initial treatment or whose disease has remained largely stable following initial chemotherapy.
Pemetrexed Eugia is also used to treat patients with advanced non-squamous non-small cell lung cancer in whom disease progression has occurred after initial treatment with other chemotherapy agents.

2. Important information before using Pemetrexed Eugia

When not to use Pemetrexed Eugia

• if the patient is allergic (hypersensitive) to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if the patient is breastfeeding; breastfeeding must be discontinued during treatment with Pemetrexed Eugia.
• in patients who have recently been vaccinated or are scheduled to be vaccinated against yellow fever.

Warnings and precautions
Before starting treatment with Pemetrexed Eugia, consult a doctor or hospital pharmacist.
If the patient currently has or has previously had kidney problems, they should consult a doctor or hospital pharmacist, as it may not be possible to receive Pemetrexed Eugia.
Before each infusion, medical staff will take blood samples from the patient to assess whether liver and kidney function are sufficient and whether blood cell counts are adequate for treatment with Pemetrexed Eugia. The doctor may decide to adjust the dose or delay treatment depending on the patient's general condition and significant drops in blood cell counts.
If the patient is also receiving cisplatin, the doctor will ensure that the patient is adequately hydrated and receives appropriate pre- and post-treatment to prevent vomiting.
Patients who have undergone or are scheduled to undergo radiotherapy should inform their doctor, as early or delayed radiation reactions may occur after administration of Pemetrexed Eugia.
Patients who have recently been vaccinated should inform their doctor, as adverse reactions may occur after administration of Pemetrexed Eugia.
Patients with current or past heart disease should inform their doctor.
If fluid has accumulated around the patient's lung, the doctor may decide to perform a procedure to remove the fluid before administering Pemetrexed Eugia.

Children and adolescents
Pemetrexed Eugia must not be used in children and adolescents, as there is no experience with the use of this medicine in patients under 18 years of age.

Pemetrexed Eugia and other medicines
Inform the doctor about all painkillers and anti-inflammatory medicines (used to treat swelling) being taken, 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 Pemetrexed Eugia infusion and/or the patient's kidney function, the doctor will advise which medicines can be taken and when. If in doubt whether a medicine belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs), ask the doctor or pharmacist.
Inform the doctor if the patient is taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lanzoprazole, pantoprazole and rabeprazole) used to treat heartburn and acid reflux.
Tell the doctor or hospital pharmacist if the patient is taking or has recently taken any other medicines, including those available without a prescription.

Pregnancy
If the patient is pregnant, suspects she may be pregnant, or is planning to have a child, she must inform her doctor. The use of Pemetrexed Eugia during pregnancy should be avoided. The doctor will inform the patient about the risks associated with using the medicine during pregnancy. Women must use an effective method of contraception during treatment with Pemetrexed Eugia and for 6 months after the last dose.

Breastfeeding
Women who are breastfeeding should inform their doctor.
Breastfeeding must be discontinued during treatment with Pemetrexed Eugia.

Effect on fertility
Men are advised not to attempt to father a child during treatment and for 3 months after completion of treatment with Pemetrexed Eugia. Men should use effective contraception during treatment with this medicine and for 3 months after its discontinuation. If a man wishes to father a child during treatment with Pemetrexed Eugia or within 3 months after completion of treatment, he should seek advice from a doctor or pharmacist. Pemetrexed Eugia may affect the ability to have children. Before starting treatment, patients may consult their doctor about sperm storage.

Driving and using machines
Pemetrexed Eugia may cause fatigue. Caution should be exercised when driving or operating machinery.

Pemetrexed Eugia contains sodium
Pemetrexed Eugia 100 mg, powder for solution for infusion
This medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

Pemetrexed Eugia 500 mg, powder for solution for infusion
This medicine contains 54 mg of sodium (main component of table salt) in each vial. This corresponds to 2.7% of the maximum recommended daily dietary intake of sodium for adults.

3. How to use Pemetrexed Eugia

The dose of Pemetrexed Eugia is 500 milligrams per square meter of the patient's body surface area.
The patient's body surface area is calculated based on measurement of height and weight.
The dose is determined according to this calculated body surface area. The dose may be adjusted or treatment delayed depending on blood cell counts and the patient's overall condition. Before administration of Pemetrexed Eugia, a hospital pharmacist, nurse, or doctor will reconstitute the powder with 9 mg/ml (0.9%) sodium chloride injection solution.
Pemetrexed Eugia is always administered as an intravenous infusion. The infusion lasts approximately 10 minutes.

Administration of Pemetrexed Eugia in combination with cisplatin:
The doctor or hospital pharmacist will calculate the dose based on the patient's height and weight. Cisplatin is also administered as an intravenous infusion and is given approximately 30 minutes after completion of the Pemetrexed Eugia infusion. The cisplatin infusion lasts about two hours.
Infusions are usually performed once every 3 weeks.

Additional medications:

Corticosteroids: Your doctor will prescribe a steroid in tablet form (in a dose equivalent to 4 milligrams of dexamethasone twice daily) which you must take on the day before treatment, on the day of the infusion, and on the following day after Pemetrexed Eugia treatment. These medications are given to reduce the frequency and severity of skin reactions that may occur during anticancer therapy.

Vitamin supplementation: Your doctor will prescribe oral folic acid (vitamin) or a multivitamin product containing folic acid (350 to 1000 micrograms) to be taken once daily during treatment with Pemetrexed Eugia. At least five doses of folic acid must be taken during the seven days preceding the first dose of Pemetrexed Eugia. Folic acid should be continued for 21 days after receiving the last dose of Pemetrexed Eugia. In the week before administration of Pemetrexed Eugia, and then at intervals of approximately 9 weeks (corresponding to three cycles of chemotherapy with Pemetrexed Eugia), patients will also receive vitamin B_(12) (1000 micrograms) by injection. Administration of vitamin B_(12) and folic acid aims to reduce possible adverse effects of anticancer drugs.

If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following symptoms occur, you should immediately inform your doctor:

• Fever or infection (appropriately often or very often): if the patient develops a fever of 38°C or higher, sweating or other signs of infection (due to the possibility of a marked decrease in white blood cell count, which is very common). Infection (sepsis) may be severe and lead to death.
• If the patient starts experiencing chest pain (often) or rapid heartbeat (uncommon).
• If the patient develops pain, redness, swelling or ulcers in the mouth (very often).
• Allergic reaction: if the patient develops a skin rash (very often), burning or stinging sensation (often), or fever (often). Skin reactions may rarely be severe and lead to death. Inform the doctor immediately if a severe rash, itching or blistering occurs (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If the patient experiences fatigue, fainting, shortness of breath or paleness (due to the possibility of a marked decrease in hemoglobin concentration, which is very common).
• If the patient experiences bleeding from the gums, nose or mouth, or any bleeding that cannot be stopped, red or pink-colored urine, or unexpected bruising (due to the possibility of a marked decrease in platelet count, which is common).
• If the patient suddenly develops shortness of breath, severe chest pain or coughing up blood-stained sputum (uncommon) (these may indicate a blood clot in the pulmonary blood vessels).

Adverse reactions of Pemetrexed Eugia may include:
Very common (may occur in more than 1 in 10 people):

• Infection
• Sore throat (pharyngitis)
• Low neutrophil count (a type of white blood cell)
• Low white blood cell count
• Low hemoglobin concentration
• Pain, redness, swelling or mouth ulcers
• Loss of appetite
• Vomiting
• Diarrhea
• Nausea
• Skin rash
• Skin desquamation (peeling)
• Abnormal blood test results indicating impaired kidney function
• Fatigue (tiredness)

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

• Blood infection (sepsis)
• Fever with low neutrophil count (a type of white blood cell)
• Low platelet count
• Allergic reaction
• Dehydration
• Taste disturbances
• Damage to motor nerves, which may lead to muscle weakness and atrophy (wasting), mainly in arms and legs
• Damage to sensory nerves, which may lead to loss of sensation, burning pain and unsteadiness when walking
• Dizziness
• Inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye)
• Dry eyes
• Watery eyes
• Dryness of the conjunctiva (the membrane lining the eyelids and covering the white of the eye) and cornea (the transparent layer covering the front of the iris and pupil)
• Swelling of the eyelids
• Eye disorders with dryness, watering, irritation and/or pain
• Heart failure (a condition causing reduced pumping strength of the heart muscle)
• Irregular heartbeat
• Indigestion
• Constipation
• Abdominal pain
• Liver: increased blood levels of chemicals produced in the liver
• Increased skin pigmentation
• Itchy skin
• Skin rash with target-like lesions resembling a bull's eye
• Hair loss
• Urticaria (hives)
• Kidney failure
• Worsening kidney function
• Fever
• Pain
• Excess fluid in body tissues causing swelling (edema)
• Chest pain
• Inflammation and ulceration of the mucous membranes lining the gastrointestinal tract

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

• Decreased number of red blood cells, white blood cells and platelets
• Stroke
• A type of stroke caused by blockage of an artery supplying blood to the brain
• Intracranial hemorrhage
• Angina pectoris (chest pain caused by reduced blood flow to the heart)
• Myocardial infarction (heart attack)
• Narrowing or blockage of the coronary arteries
• Rapid heartbeat
• Inadequate blood supply to the limbs
• Blockage of one of the pulmonary arteries in the patient's lungs
• Inflammation and scarring of the membrane lining the lungs, with breathing disturbances
• Passage of bright red blood from the anus
• Gastrointestinal bleeding
• Perforation of the intestinal wall
• Inflammation of the membrane lining the esophagus
• Inflammation of the membrane lining the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only when used in combination with cisplatin)
• Inflammation, swelling, redness and erosions of the esophageal mucosa caused by radiotherapy
• Radiation-induced lung inflammation

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

• Hemolysis (breakdown of red blood cells)
• Anaphylactic shock (severe allergic reaction)
• Inflammation of the liver
• Skin redness
• Skin rash appearing in previously irradiated skin areas

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

• Skin and soft tissue infections
• Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction which may be life-threatening)
• Toxic epidermal necrolysis (a type of severe skin reaction which may be life-threatening)
• Autoimmune disorders causing rash and blistering skin lesions on the legs, arms and abdomen
• Skin inflammation characterized by fluid-filled blisters
• Fragile skin, presence of blisters and erosions, and skin scarring
• Redness, pain and swelling, mainly in the lower limbs
• Inflammation of the skin and subcutaneous fat tissue (cellulitis-like condition)
• Skin inflammation (dermatitis)
• Inflammatory condition of the skin with itching, redness, cracking and roughness
• Intensely itchy skin lesions

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

• Diabetes mellitus caused primarily by kidney pathology
• Kidney disorders leading to necrosis of renal tubular epithelial cells

Any of these symptoms and/or conditions may occur. You should inform your doctor as soon as possible if any of these adverse reactions appear.
Inform your doctor if you are concerned about any of these symptoms.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of this medicine.
Adverse reactions may also be reported to the responsible entity.

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 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 requirements for storage of the medicinal product.
Reconstituted and diluted solution for infusion: Chemical and physical stability of pemetrexed solutions has been demonstrated for 24 hours at 2°C - 8°C after reconstitution and dilution for infusion.
From a microbiological point of view, the product should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration prior to use, which should not usually exceed 24 hours at a temperature of 2°C to 8°C.
Do not use this medicine if signs of deterioration are apparent.
This medicine is for single use only.
Medicines must 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 package 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 solution after reconstitution contains 25 mg/ml of pemetrexed. Further dilution by a healthcare professional is required prior to 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.
A lyophilized cake or white to slightly yellow or greenish-yellow powder.
The medicine is available in packs containing 1 vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer/Importer
Marketing Authorisation 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 medicinal product is authorised in the European Economic Area under the following names:
Belgium: Pemetrexed Eugia 500 mg/ 1000 mg powder for concentrate for solution for infusion / powder for solution to be diluted for perfusion / powder for concentrate for solution for infusion
Denmark: Pemetrexed Aurobindo
France: PEMETREXED ARROW 100 mg/ 500 mg/ 1000 mg powder for solution to be diluted for perfusion
Germany: Pemetrexed PUREN 100 mg/ 500 mg/ 1000 mg powder for preparation of a concentrate for solution for infusion
Italy: Pemetrexed Aurobindo
Poland: Pemetrexed Eugia
Portugal: Pemetrexed Eugia

The following information is intended exclusively for medical professionals or

healthcare personnel:
Instructions for preparation, administration, and disposal of the drug.

1. Preparation of the pemetrexed solution and further dilution for intravenous infusion must be carried out under aseptic conditions.
2. Calculate the required dose and the number of vials of Pemetrexed Eugia needed. Each vial contains an overage of pemetrexed to ensure delivery of the labeled amount.
3. Pemetrexed Eugia, 100 mg: Reconstitute the contents of each 100 mg vial with 4.2 ml of sodium chloride injection solution, 9 mg/ml (0.9%), without preservatives. The resulting solution contains 25 mg/ml of pemetrexed.

Pemetrexed Eugia, 500 mg:
Reconstitute the contents of each 500 mg vial with 20 ml of sodium chloride injection solution, 9 mg/ml (0.9%), without preservatives. The resulting solution contains 25 mg/ml of pemetrexed.
Gently rotate each vial until the powder is completely dissolved.
The prepared solution is clear, ranging in color from colorless to yellow or yellow-green, which does not negatively affect the product quality. The pH of the prepared solution ranges from 6.6 to 7.8. Further dilution is required.

4. Dilute the appropriate volume of the prepared pemetrexed solution to a final volume of 100 ml using sodium chloride injection solution, 9 mg/ml (0.9%), without preservatives, for intravenous infusion administered over 10 minutes.
5. Pemetrexed solutions for infusion prepared as described above are compatible with infusion sets and bags with polyvinyl chloride and polyolefin linings. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer's solution and Ringer's injection solution.
6. Prior to parenteral administration, visually inspect the drug solution for particulate matter and discoloration. If visible particles are present in the solution, the drug must not be administered.
7. Pemetrexed solutions are intended for single use only. Any unused product or waste material must be disposed of in accordance with applicable local regulations.

Storage
Chemical and physical in-use stability of pemetrexed solutions has been demonstrated for 24 hours at 2°C - 8°C following reconstitution and dilution.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the end user and should generally not exceed 24 hours at 2°C to 8°C, unless reconstitution/dilution was performed under controlled and validated aseptic conditions.

Precautions for preparation and administration of the drug
As with other potentially toxic antineoplastic agents, caution should be exercised when handling and preparing pemetrexed infusion solutions. The use of gloves is recommended. In case of contact of the pemetrexed solution with the skin, wash the skin immediately and thoroughly with soap and water. In case of contact with mucous membranes, thoroughly rinse the affected area with water. Pemetrexed is not a vesicant. There is no known specific antidote in the event of extravasation. There have been several reported cases of pemetrexed extravasation, none of which were assessed by investigators as serious.

In the event of extravasation, manage according to established guidelines, as with extravasation of other non-vesicant substances.