Pemetrexed Ever Pharma

Package Leaflet: Information for the User

Pemetrexed EVER Pharma, 25 mg/ml, 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.
• 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

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

1. What Pemetrexed EVER Pharma is and what it is used for

Pemetrexed EVER Pharma is a medicine used in the treatment of cancer. It contains the active substance pemetrexed. Pemetrexed belongs to a group of medicines called antifolate medicines. It works by interfering with the growth and spread of cancer cells.

Pemetrexed EVER Pharma, in combination with another anticancer 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 EVER Pharma, in combination with cisplatin, is also used as a first-line treatment for patients with advanced non-small cell lung cancer.

Pemetrexed EVER Pharma may be used alone for the treatment of patients with advanced non-small cell lung cancer who have already received chemotherapy.

Pemetrexed EVER Pharma is also used for the treatment of patients with advanced non-small cell lung cancer whose disease has progressed after prior chemotherapy.

2. What you need to know before you use Pemetrexed EVER Pharma

When you should not use Pemetrexed EVER Pharma:

• If you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• If you are breast-feeding, you must stop breast-feeding before starting treatment with Pemetrexed EVER Pharma.
• In patients who have recently been vaccinated or are about to be vaccinated against yellow fever.

Warnings and precautions

Before starting treatment with Pemetrexed EVER Pharma, you should discuss your medical history and any other treatments you are receiving with your doctor or pharmacist.

Patients who have had or currently have kidney problems should inform their doctor or hospital pharmacist, as this may mean that Pemetrexed EVER Pharma cannot be used.

Before each infusion, medical staff will take blood samples from you to check your liver and kidney function and to check that you have enough blood cells to receive Pemetrexed EVER Pharma. Depending on your overall condition and kidney function, your doctor may adjust the dose or delay treatment.

If you are also being treated with cisplatin, your doctor will check your hydration status and recommend appropriate treatment to prevent vomiting.

Patients who have received or are going to receive radiation therapy should inform their doctor, as there may be an early or late radiation reaction with Pemetrexed EVER Pharma.

Patients who have recently been vaccinated should inform their doctor, as this may cause side effects in combination with Pemetrexed EVER Pharma.

Patients with heart disease should inform their doctor.

In case of fluid accumulation around the lungs, your doctor may decide to perform a procedure to drain the fluid before administering Pemetrexed EVER Pharma.

Children and adolescents

There are no indications for the use of Pemetrexed EVER Pharma in children and adolescents.

Pemetrexed EVER Pharma with other medicines

Tell your doctor or hospital pharmacist about all the medicines you are taking, including medicines obtained without a prescription, such as painkillers and anti-inflammatory medicines (e.g., those that prevent swelling), including non-steroidal anti-inflammatory drugs (NSAIDs), such as 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 EVER Pharma and/or your kidney function, your doctor will advise you on which medicines you can take and when.

If you are in doubt whether the medicines you are taking 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 proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) used to treat heartburn and acid reflux.

As with other anticancer medicines, it is not recommended to use Pemetrexed EVER Pharma with live attenuated vaccines.

Whenever possible, inactivated vaccines should be used.

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.

Pemetrexed EVER Pharma should not be used during pregnancy.

Your doctor will inform you about the potential risk of using Pemetrexed EVER Pharma during pregnancy.

During treatment with Pemetrexed EVER Pharma and for 6 months after the last dose, women must use effective contraception.

Breast-feeding

If you are breast-feeding, tell your doctor.

During treatment with Pemetrexed EVER Pharma, you must stop breast-feeding.

Fertility

Men are advised not to father a child during treatment and for 3 months after the last dose of Pemetrexed EVER Pharma and to use effective contraception during this time.

If a man wishes to father a child during treatment or within 3 months after the last dose, he should consult his doctor or pharmacist.

Pemetrexed EVER Pharma may affect fertility.

Before starting treatment, patients may consult their doctor for advice on sperm preservation.

Driving and using machines

Pemetrexed EVER Pharma may cause fatigue.

You should be careful when driving or operating machinery.

Pemetrexed EVER Pharma contains sodium

This medicine contains 96.6 mg of sodium (the main component of common salt) per 500 mg dose of pemetrexed per square meter of body surface area.

This corresponds to 4.8% of the maximum recommended daily intake of sodium for adults.

3. How to use Pemetrexed EVER Pharma

Pemetrexed EVER Pharma will always be administered by a qualified healthcare professional.

The recommended dose of Pemetrexed EVER Pharma 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 doctor will determine the dose based on the calculated body surface area.

The dose may be adjusted or treatment delayed, depending on the results of blood tests and the patient's overall condition.

Before administration, the hospital pharmacist, nurse, or doctor will mix the concentrate with 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.

Pemetrexed EVER Pharma is always administered as an intravenous infusion.

The infusion lasts about 10 minutes.

Use of Pemetrexed EVER Pharma 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.

The cisplatin infusion starts about 30 minutes after the end of the Pemetrexed EVER Pharma infusion and lasts about 2 hours.

The infusion will usually be performed every 3 weeks.

Additional medicines:

Corticosteroids: The doctor will prescribe steroids in tablet form (equivalent to 4 milligrams of dexamethasone twice a day), which should be taken the day before, the day of, and the day after Pemetrexed EVER Pharma 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 Pemetrexed EVER Pharma.

During the 7 days preceding the first dose of Pemetrexed EVER Pharma, you should take at least 5 doses of folic acid.

Folic acid should be continued for 21 days after the last dose of Pemetrexed EVER Pharma.

Vitamin B12 (1000 micrograms) will also be administered by injection during the week preceding Pemetrexed EVER Pharma administration and then at intervals of about 9 weeks (corresponding to 3 cycles of chemotherapy with Pemetrexed EVER Pharma).

The administration of vitamin B12 and folic acid is intended to reduce the possible side effects of anticancer medicines.

Your condition will be closely monitored during treatment with Pemetrexed EVER Pharma.

This monitoring will routinely include blood tests and liver and kidney function tests.

The dose of Pemetrexed EVER Pharma may be adjusted or treatment delayed, depending on the results of these tests.

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

4. Possible side effects

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

If you experience any of the following symptoms, tell your doctor immediately:

• Fever or infection (very common): 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 the number of white blood cells, which is a very common side effect).
• Chest pain (common) or rapid heartbeat (uncommon).
• Pain, redness, swelling, or ulcers in the mouth (very common).
• Allergic reaction: skin rash (very common), burning sensation or tingling (common), or fever (common).
• Feeling tired, fainting, shortness of breath, or pale skin (due to the possibility of a significant decrease in hemoglobin levels, which is a very common side effect).
• Bleeding from the gums, nose, or mouth, or other bleeding that cannot be stopped, red or pink urine, or unexpected bruising on the skin (due to the possibility of a significant decrease in platelet count, which is a very common side effect).
• Sudden shortness of breath, severe chest pain, or coughing up blood (uncommon) (may indicate the presence of blood clots in the lungs).

Very common side effects (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, or ulcers in the mouth
• Loss of appetite
• Vomiting
• Diarrhea
• Nausea
• Skin rash
• Peeling skin
• Abnormal blood test results indicating impaired kidney function
• Fatigue

Common side effects (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 reactions
• Dehydration
• Taste disturbances
• Nerve damage that can cause weakness and wasting of muscles, especially in the arms and legs
• Nerve damage that can cause loss of sensation, burning pain, and unsteady gait
• Dizziness
• Inflammation or swelling of the eyes
• Dry eye syndrome
• Excessive tearing
• Dryness of the eyes and cornea (the clear layer on the front of the eye)
• Swelling of the eyelids
• Eyelid problems with dryness, tearing, irritation, and/or pain
• Heart failure (a condition that weakens the heart's pumping ability)
• Irregular heartbeat
• Indigestion
• Constipation
• Abdominal pain
• Liver problems: increased levels of liver enzymes in the blood
• Increased skin pigmentation
• Itching skin
• Ring-shaped skin rash
• Hives
• Kidney failure
• Impaired kidney function
• Fever
• Pain
• Excessive fluid accumulation in the tissues, causing swelling
• Chest pain
• Inflammation and ulcers of the mucous membranes lining the digestive tract

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

• Low 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
• Chest pain caused by reduced blood flow to the heart
• Heart attack
• Narrowing or blockage of the coronary arteries
• Abnormal heart rhythms
• Insufficient blood flow to the limbs
• Blockage of a blood vessel in the lungs
• Inflammation and scarring of the lining of the lungs, with breathing difficulties
• Bleeding from the rectum
• Bleeding from the digestive tract
• Perforation of the intestine
• Inflammation of the esophagus
• Inflammation of the lining of the colon, which may be accompanied by bleeding from the intestines or rectum (observed only in combination with cisplatin)
• Inflammation, swelling, redness, and ulcers of the mucous membranes of the esophagus caused by radiation therapy
• Radiation-induced lung inflammation

Rare side effects (may affect up to 1 in 1000 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 side effects (may affect up to 1 in 10,000 people):

• Infections of the skin and underlying tissue
• 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 that cause skin rash and blistering on the skin of the legs, arms, and abdomen
• Inflammation of the skin with blistering
• Easily damaged skin, with blisters and scarring
• Redness, pain, and swelling, mainly in the lower limbs
• Inflammation of the skin and underlying fatty tissue (pseudoscleroderma)
• Skin inflammation
• Inflammation, itching, redness, cracking, and roughness 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 that causes the death of kidney cells

If you experience any of these symptoms, tell your doctor as soon as possible.

Talk to your doctor if you are concerned about any of these side effects.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet.

Side effects can be reported to the national reporting system listed below.

You can also report side effects directly via the national reporting system.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pemetrexed EVER Pharma

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 and carton after EXP.

The expiry date refers to the last day of that month.

Do not freeze.

Infusion solution after dilution: After dilution, the physical and chemical stability of the prepared solutions and diluted infusion solutions of pemetrexed have been demonstrated for 28 days when stored in a refrigerator at 2°C to 8°C and for 7 days at 20°C to 30°C.

From a microbiological point of view, the product should be used immediately.

If not used immediately, the in-use storage times and conditions are the responsibility of the user: the solution should be stored in a refrigerator at 2°C to 8°C for a maximum of 24 hours, unless dilution has been made in controlled and validated aseptic conditions.

Pemetrexed EVER Pharma should not be used if it contains solid particles or other visible signs of deterioration.

This medicine is for single use only.

Any unused solution should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Pemetrexed EVER Pharma contains

The active substance is pemetrexed.

One milliliter of the concentrate contains 25 mg of pemetrexed (as pemetrexed disodium).

One vial with 4 ml of concentrate contains 100 mg of pemetrexed (as pemetrexed disodium).

One vial with 20 ml of concentrate contains 500 mg of pemetrexed (as pemetrexed disodium).

One vial with 40 ml of concentrate contains 1000 mg of pemetrexed (as pemetrexed disodium).

The other ingredients are trometamol, monothioglycerol, citric acid, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injections.

What Pemetrexed EVER Pharma looks like and contents of the pack

Pemetrexed EVER Pharma is a clear, colorless to pale yellow solution.

Pemetrexed EVER Pharma is supplied in vials made of colorless glass, closed with a bromobutyl rubber stopper, and sealed with an aluminum flip-off cap, with or without a protective sleeve, in a cardboard box.

Each pack contains one vial of Pemetrexed EVER Pharma.

Pack sizes:

1 x 4 ml vial (100 mg/4 ml)

1 x 20 ml vial (500 mg/20 ml)

1 x 40 ml vial (1000 mg/40 ml)

Not all pack sizes may be marketed.

Marketing Authorization Holder

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Manufacturer

EVER Pharma Jena GmbH

Otto Schott Street 15

07745 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

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

Date of last revision of the package leaflet: 12.2024

Information intended for healthcare professionals only:

For full information, see the Summary of Product Characteristics.

Pregnant women should not handle this medicine.

Instructions for preparation, administration, and disposal of the medicinal product

• 1. Preparation of pemetrexed solution and further dilution of the solution for intravenous infusion should be performed under aseptic conditions.
• 2. Calculate the dose and the number of vials of Pemetrexed EVER Pharma required.
• 3. The appropriate volume of Pemetrexed EVER Pharma should be diluted to a volume of 100 ml using sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution without preservatives.
• 4. Pemetrexed EVER Pharma is incompatible with diluents containing calcium, including Ringer's solution and lactated Ringer's solution.
• 5. Before parenteral administration, the solution should be inspected visually for particulate matter and discolouration.
• 6. Pemetrexed EVER Pharma solutions are for single use only.
• 7. Any unused product or waste material should be disposed of in accordance with local requirements.

Precautions for handling and administration:

As with other potentially toxic anticancer agents, caution should be exercised when handling and preparing Pemetrexed EVER Pharma solutions for infusion.

Gloves should be worn.

In case of skin contact with pemetrexed solution, the area should be washed immediately and thoroughly with soap and water.

In case of contact with the mucous membranes, the area should be flushed with water.

Pemetrexed does not cause vesiculation.

No specific antidote has been identified in the event of an overdose of pemetrexed.

There have been few reports of extravasation of pemetrexed.

In the event of extravasation, the area should be managed according to standard procedures, as with other non-vesicant drugs.