Label: Information for the User

Pemetrexed Fresenius Kabi 25 mg/ml Concentrate for Solution for InfusionEFGpemetrexed

Read this label carefully before starting to receive this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Pemetrexed Fresenius Kabi is a medication used for the treatment of cancer.

Pemetrexed Fresenius Kabi can be administered with cisplatino, another anticancer medication, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lung lining, in patients who have not received prior chemotherapy.

Pemetrexed Fresenius Kabi can also be administered, with cisplatino, for the initial treatment of patients in advanced stages of lung cancer.

Pemetrexed Fresenius Kabi may be prescribed if you have advanced lung cancer, if your disease has responded to treatment or if it remains unchanged after initial chemotherapy.

Pemetrexed Fresenius Kabi can also be administered for the treatment of patients in advanced stages of lung cancer whose disease has progressed, who have already received initial chemotherapy treatment.

Do not use Pemetrexed Fresenius Kabi

• if you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding, you should stop breastfeeding during treatment with Pemetrexed Fresenius Kabi.
• if you have recently been given or are to be given the yellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before Pemetrexed Fresenius Kabi is administered to you.

If you have or have had kidney problems, tell your doctor or hospital pharmacist as it may be possible that you cannot receive Pemetrexed Fresenius Kabi.

Before each infusion, you will have to give blood samples to evaluate if your renal and hepatic function is sufficient and to evaluate if you have enough blood cells to receive Pemetrexed Fresenius Kabi. Your doctor may decide to change your dose or delay treatment depending on your general condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will ensure that you are properly hydrated and receive the appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are to receive radiation therapy, please consult your doctor, as there may be an early or late reaction between the radiation and Pemetrexed Fresenius Kabi.

If you have recently been vaccinated, please consult your doctor, as it may cause some negative effect with Pemetrexed Fresenius Kabi.

If you have heart disease or a history of heart disease, please consult your doctor.

If you have fluid accumulated around your lung, your doctor may decide to drain the fluid before administering Pemetrexed Fresenius Kabi.

Children and adolescents

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

Use of Pemetrexed Fresenius Kabi with other medicines

Inform your doctor if you are using pain or inflammation medicines (such as non-steroidal anti-inflammatory drugs, or 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 Fresenius Kabi infusion and/or your renal function, your doctor will advise you which medicines you can use and when. If you are unsure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

Inform 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.

Inform your doctor or hospital pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

Pregnancy

If you are pregnant, think you may be pregnant or intend to become pregnant, inform your doctor. During pregnancy, the use of Pemetrexed Fresenius Kabi should be avoided. Your doctor will inform you of the possible risks of taking Pemetrexed Fresenius Kabi during pregnancy. Women should use effective contraceptive methods during treatment with Pemetrexed Fresenius Kabi and for 6 months after the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with Pemetrexed Fresenius Kabi, breastfeeding should be stopped.

Fertility

Men are advised not to father a child during and for 3 months after treatment with Pemetrexed Fresenius Kabi and should use effective contraceptive methods during and for 3 months after treatment with Pemetrexed Fresenius Kabi. If you wish to father a child during treatment or in the 3 months following treatment, consult your doctor or pharmacist. Pemetrexed Fresenius Kabi may affect your ability to father children. Talk to your doctor about sperm conservation before starting your treatment.

Driving and operating machines

Pemetrexed Fresenius Kabi may make you feel tired. Be careful when driving a vehicle or operating machines.

Pemetrexed Fresenius Kabi contains 964 mg of hydroxypropylbeta-cyclodextrin per 100 mg of pemetrexed.

If you have kidney disease, consult your doctor before this medicine is administered to you.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The dose of Pemetrexed Fresenius Kabi is 500 milligrams per square meter of the surface of your body. They will measure your height and weight to calculate your body surface. Your doctor will use this surface to calculate the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell count and overall condition. The hospital pharmacist, nurse, or doctor will have mixed Pemetrexed Fresenius Kabi with a injectable solution of sodium chloride 9 mg/ml (0.9%) or a solution for intravenous infusion of glucose 5%, before it is administered to you.

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

When using Pemetrexed Fresenius Kabi in combination with cisplatin:

Your doctor or the hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also administered through an infusion in one of your veins and is given approximately 30 minutes after you have finished the infusion of Pemetrexed Fresenius Kabi. The cisplatin infusion lasts approximately two hours.

You should normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe some tablets of steroids (equivalent to 4 milligrams of dexamethasone twice a day) that you will have to take the day before, the same day, and the day after treatment with Pemetrexed Fresenius Kabi. Your doctor gives you this medication 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 Fresenius Kabi. You should take at least five doses during the seven days before the first dose of Pemetrexed Fresenius Kabi. You should continue taking folic acid for 21 days after the last dose of Pemetrexed Fresenius Kabi. Additionally, you will receive an injection of vitamin B12 (1,000 micrograms) the week before administration of Pemetrexed Fresenius Kabi and approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Fresenius Kabi). Vitamin B12 and folic acid are given to reduce possible toxic effects of cancer treatment.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

You should inform your doctor immediately if you notice any of the following symptoms:

• Fever or infection (frequent or very frequent, respectively): if you have a temperature of 38°C or higher, sweatingor other signs of infection (since you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and cause death.
• If you start to feel chest pain (frequent) or your heart rate is faster (rare).
• If you have pain, redness, swelling, or sores in your mouth (very frequent).
• Allergic reaction: if you develop hives (very frequent), burning sensation or itching (frequent), or fever (frequent). In rare cases, skin reactions can be severe and may cause death. Contact your doctor if you present severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you lack breath or are pale (because you have fewer hemoglobin than normal, which is very frequent).
• If you experience bleeding gums, nose, or mouth or any bleeding that does not stop, pink or red urine, or unexpected bruises (because you have fewer platelets than normal, which is very frequent).
• If you experience sudden difficulty breathing, intense chest pain, or coughing up blood (rare) (may indicate that there is a blood clot in the pulmonary veins).

Other side effects with pemetrexed may include:

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

Infection

Pharyngitis (sore throat)

Low count of neutrophil granulocytes (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

Dry skin

Abnormal blood test results showing reduced kidney function

Weakness (fatigue)

Frequent (may affect up to 1 in 10 people)

Blood infection

Fever with low neutrophil granulocyte count (a type of leukocyte)

Low platelet count

Allergic reaction

Fluid loss

Alteration in taste

Damage to motor nerves that may cause muscle weakness and atrophy (mainly in arms and legs)

Damage to sensory nerves that may cause numbness, burning sensation, and unstable gait

Dizziness

Conjunctival inflammation or swelling (membrane covering the eyelids and covering the white part of the eye)

Eye dryness

Runny eyes

Eye dryness and corneal dryness (transparent layer in front of the iris and pupil)

Swelling of the eyelids

Ocular disorder with dryness, tearing, irritation, and/or pain

Heart failure (condition affecting the heart's pumping ability)

Irregular heart rhythm

Indigestion

Constipation

Abdominal pain

Liver: increased substances in the blood produced by the liver

Increased skin pigmentation

Itching skin

Rash on the body where each lesion resembles a target

Hair loss

Urticaria

Renal failure

Reduced renal function

Fever

Pain

Excess fluid in the body tissue causing swelling

Chest pain

Inflammation and ulceration of the mucous membranes covering the internal digestive tract

Rare (may affect up to 1 in 100 people)

Reduction in the number of red blood cells, white blood cells, and platelets

Ischemia or lack of blood flow

Ischemia due to blockage of a cerebral artery

Intracranial bleeding

Angina (chest pain caused by reduced blood flow to the heart)

Myocardial infarction

Coronary artery narrowing or blockage

Increased heart rate

Poor blood distribution to the extremities

Obstruction in one of the pulmonary arteries in the lungs

Inflammation and scarring of the lung mucosa with respiratory problems

Bright red blood loss through the anus

Bleeding in the gastrointestinal tract

Intestinal perforation

Inflammation of the esophageal mucosa

Inflammation of the large intestine mucosa, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)

Inflammation, edema, erythema, and erosion of the esophageal mucosa surface caused by radiation therapy

Inflammation of the lung caused by radiation therapy

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

Red blood cell destruction

Anaphylactic shock (severe allergic reaction)

Inflammatory liver disease

Skin redness

Rash on the skin that develops in a previously irradiated area

Extremely 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 causing skin eruptions and blisters on the legs, arms, and abdomen

Inflammation of the skin characterized by the presence of blisters filled with fluid

Skin fragility, blisters, and erosions, and skin scars

Redness, pain, and swelling mainly in the lower limbs

Inflammation of the skin and subcutaneous fat (pseudocelulitis)

Inflammation of the skin (dermatitis)

The skin becomes inflamed, itches, reddens, cracks, and becomes rough

Intensely itchy spots

Unknown frequency:the frequency cannot be estimated from the available data

A type of diabetes primarily caused by kidney disease

Kidney disorder involving the death of tubular epithelial cells that form the renal tubules

You may experience some of these symptoms and/or situations. Inform your doctor as soon as you start experiencing any of these side effects.

If you are concerned about any side effect, consult with your doctor.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the box after CAD. The expiration date is the last day of the month indicated.

Store below 25°C.

Keep the vial in the outer packaging to protect it from light.

Infusion solution: the medication must be used immediately. When prepared as indicated, the chemical and physical stability of the diluted pemetrexed solution has been demonstrated for 21 days in refrigeration and for 7 days at room temperature.

Do not use this medication if it presents particles.

This medication is for single use only.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Pemetrexed Fresenius Kabi

The active ingredient is pemetrexed.

One milliliter of concentrate contains 25 mg of pemetrexed.

After dilution, avial of 4 ml concentrate contains 100 mg of pemetrexed (as pemetrexed diacid).

Onevial of 20 ml concentrate contains 500 mg of pemetrexed (as pemetrexed diacid).

Onevial of 40 ml concentrate contains 1,000 mg of pemetrexed (as pemetrexed diacid).

The other components are hydroxypropylbeta cyclodextrin, hydrochloric acid, tromethamine, and water for injection.

Appearance of the product and contents of the package

Pemetrexed Fresenius Kabi is a concentrate for solution for infusion (sterile concentrate) in a glass vial. It is a transparent to slightly yellowish or yellowish-green solution.

It is available in packs of 1 vial.

Marketing Authorization Holder

Fresenius Kabi Deutschland GmbH

Else-Kröner-Straße 1,

61352 Bad Homburg v.d.Höhe

Germany

Responsible Person

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

Or

Fresenius Kabi Polska Sp. z o.o.

ul. Sienkiewicza 25, Kutno, 99-300

Poland

You can request more information about this medicine by contacting the marketing authorization holder.

Last review date of this leaflet:

Other sources of information

The detailed information about this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/

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This information is intended solely for healthcare professionals:

Instructions for use and handling and disposal

• Use aseptic techniques during the dilution of pemetrexed for administration by intravenous infusion.

• Calculate the dose and number of vials of Pemetrexed Fresenius Kabi required.

• The appropriate volume of Pemetrexed Fresenius Kabi should be diluted to 100 ml with sodium chloride 9 mg/ml (0.9%) injection or intravenous infusion solution of glucose 5% and administered as an intravenous infusion over 10 minutes.

• The pemetrexed infusion solution prepared according to the above indications is compatible with polyvinyl chloride and polyolefin infusion systems and bags. Pemetrexed is incompatible with calcium-containing diluents, including lactated Ringer's injection and Ringer's injection.

Pemetrexed Fresenius Kabi contains tromethamine as an excipient. Tromethamine is incompatible with cisplatin, causing its degradation. This medicine should not be mixed with other medications. Intravenous lines should be flushed after administration of Pemetrexed Fresenius Kabi.

• Parenteral medications should be visually inspected before administration to discard the appearance of particles or alteration of color. If particles are observed, the medication should not be administered.

• Pemetrexed solutions are for single use. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Precautions in preparation and administration:Like any other potentially toxic antineoplastic agentspecial care should be taken in the handling and preparation of pemetrexed infusion solutions. The use of gloves is recommended for handling. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and abundantly with water and soap. If pemetrexed solutions come into contact with mucous membranes, wash with abundant water. Pregnant women should avoid contact with cytostatic drugs. Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. 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 non-vesicant drugs.