Prospect: information for the user

Pemetrexed SUN 100 mg powder for concentrate for solution for infusion EFG

Pemetrexed SUN 500 mg powder for concentrate for solution for infusion EFG

Pemetrexed SUN 1.000 mg powder for concentrate for solution for infusion

pemetrexed

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

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

Pemetrexed SUN contains the active ingredient pemetrexed, which belongs to a group of medicines used for cancer treatment. It is used:

-in combination with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lung lining, in patients who have not received prior chemotherapy.

-in combination with cisplatin, for the initial treatment of patients with advanced stages of lung cancer.

-for the treatment of patients with advanced lung cancer, whose disease has responded to treatment or remains unchanged after initial chemotherapy.

-for the treatment of those patients with advanced lung cancer whose disease has progressed, who have already received initial chemotherapy treatment.

No use Pemetrexed SUN

• If you are allergic (hypersensitive) to pemetrexed or to any of the other components of this medicine (listed in section 6).
• If you are breastfeeding, you must interrupt breastfeeding during treatment with Pemetrexed SUN.
• If you have recently been given or are to be given the yellow fever vaccine.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Pemetrexed SUN.

-If you have had or have kidney problems, you may not be able to receive Pemetrexed SUN.

Before each infusion, you will have to give blood samples to see if your kidney and liver function is sufficient and to evaluate if you have enough blood cells to receive Pemetrexed SUN. Your doctor may decide to change your dose or delay treatment depending on your overall 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 SUN.
• If you have recently been vaccinated, please consult your doctor, as it may cause some negative effect with Pemetrexed SUN.
• If you have a heart disease or a history of heart disease.
• If you have fluid accumulated around the lung, your doctor may decide to drain the fluid before administering Pemetrexed SUN.

Children and adolescents

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

Use of Pemetrexed SUN with other medicines

Inform your doctor or hospital pharmacist if you are taking, have taken recently or may have to take any other medicine, including those purchased without a prescription.

Please inform your doctor or hospital pharmacist if you are taking

• Medicines for pain or inflammation (swelling), such as non-steroidal anti-inflammatory drugs (NSAIDs), including those purchased without a prescription (such as ibuprofen).

There are many types of NSAIDs with different durations of action. Based on the date of your Pemetrexed SUN infusion and/or your kidney 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.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant or intend to become pregnant, consult your doctor before using this medicine.

Pemetrexed SUN should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking Pemetrexed SUN during pregnancy. Women should use effective contraceptive methods during treatment with Pemetrexed SUN and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor. During treatment with Pemetrexed SUN, breastfeeding should be interrupted.

Fertility

Men are advised not to father a child during and for 6 months after treatment with Pemetrexed SUN, and therefore should use effective contraceptive methods during and for 3 months after treatment with Pemetrexed SUN. If you wish to have a child during treatment or in the 3 months following treatment, consult your doctor or pharmacist.Pemetrexed SUN may affect your ability to have children. Talk to your doctor about conserving sperm before starting treatment.

Driving and operating machinery

Pemetrexed SUN may make you feel tired. Be careful when driving a vehicle or operating machinery.

Pemetrexed SUN contains sodium

Pemetrexed SUN 100 mg contains less than 23 mg of sodium (1 mmol) per vial, which is essentially "sodium-free".

Pemetrexed SUN 500 mg contains approximately 54 mg of sodium (main component of table salt/for cooking) in each vial, which is equivalent to 2.7% of the maximum daily sodium intake recommended for an adult.

Pemetrexed SUN 1000 mg contains approximately 108 mg of sodium (main component of table salt/for cooking) in each vial, which is equivalent to 5.4% of the maximum daily sodium intake recommended for an adult.

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

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

When using Pemetrexed SUN in combination with cisplatin:

• Your doctor or 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 Pemetrexed SUN infusion. 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 steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will have to take the day before, on the same day, and the day after treatment with Pemetrexed SUN. 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 SUN. You must take at least five doses during the seven days before the first dose of Pemetrexed SUN. You must continue taking folic acid for 21 days after the last dose of Pemetrexed SUN. You will also receive an injection of vitamin B12 (1,000 micrograms) the week before administration of Pemetrexed SUN and approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed SUN). Vitamin B12 and folic acid are given to reduce possible toxic effects of cancer treatment.

If you have any other questions 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.

Severe side effects

Inform your doctor immediately if you notice any of the following severe side effects:

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

• mouth pain, redness, swelling, or sores
• allergic reaction: if you develop hives. In rare cases, skin reactions can be severe and life-threatening.
• low hemoglobin levels (anemia). You may feel tired or dizzy, if you lack breath or are pale

Common (may affect up to 1 in 10 people)

• fever or infection: if you have a temperature of 38°C or higher, sweating, or other signs of infection (since you could have fewer white blood cells than normal, which is very common). Infections (sepsis) can be severe and life-threatening.
• chest pain
• allergic reaction: burning sensation or itching and fever
• low platelet count. You may have bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruises

Uncommon (may affect up to 1 in 100 people)

• rapid heart rate
• blood clot in the lungs' veins (pulmonary embolism). If you experience sudden difficulty breathing, intense chest pain, or coughing up blood in your sputum

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

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

Other side effects

Inform your doctor as soon as possible if you notice any of the following side effects:

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

• infection
• sore throat
• low neutrophil granulocyte count (a type of white blood cell)
• low white blood cell count
• low hemoglobin levels
• mouth pain, redness, swelling, or sores
• loss of appetite
• vomiting
• diarrhea
• nausea
• skin rash
• scaly skin
• alteration in blood tests showing reduced kidney function
• asthenia (fatigue)

Common (may affect up to 1 in 10 people)

• blood infection
• fever with low neutrophil granulocytosis (a type of leukocyte)
• low platelet count
• allergic reaction
• fluid loss from the body
• alteration in taste
• motor nerve damage that can cause muscle weakness or atrophy (mainly in arms and legs)
• sensory nerve damage that can cause numbness, burning sensation (dolor urente), and unstable gait
• dizziness
• conjunctival inflammation or swelling (membrane covering the eyelids and the white part of the eye)
• dry eye
• tearful eyes
• dryness of the conjunctiva (membrane inside the eyelids and covering the white part of the eye) and cornea (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
• skin pigmentation increase
• skin 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 digestive tract internally

Uncommon (may affect up to 1 in 100 people)

• reduction in the number of red blood cells, white blood cells, and platelets
• ischemia
• ischemia due to blockage of a cerebral artery
• intracranial hemorrhage
• angina (chest pain caused by reduced blood flow to the heart)
• infarction
• coronary artery stenosis or blockage
• increased heart rate
• deficient 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
• esophageal mucosa inflammation
• inflammation of the large intestine mucosa, which may be accompanied by intestinal or rectal bleeding (visible only in combination with cisplatin)
• inflammation, edema, erythema, and erosion of the esophageal mucosa surface caused by radiation therapy
• lung inflammation caused by radiation therapy

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

• red blood cell destruction
• anaphylactic shock (severe allergic reaction)
• inflammatory liver disease
• skin redness
• skin rash developing in an area previously irradiated

Very 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 rashes and blisters on the legs, arms, and abdomen
• inflammation of the skin characterized by the presence of blisters filled with fluid
• fragility of the skin, blisters, and erosions, and skin scars
• redness, pain, and swelling mainly in the lower limbs
• inflammation of the skin and subcutaneous fat (pseudocelulitis)
• skin inflammation (dermatitis)
• the skin becomes inflamed, itches, reddens, cracks, and becomes rough
• intensely itchy spots

Unknown frequency (cannot be estimated from 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.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Ask your doctor, pharmacist, or nurse how to properly conserve Pemetrexed SUN.

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

Do not use this medication after the expiration date that appears on the vial or on the packaging after CAD. The expiration date is the last day of the month indicated.

This medication does not require any special conditions for conservation.

After opening the vial, the medication must be used immediately to avoid microbial contamination. If not used immediately, the time and conservation conditions are the responsibility of the user and should not exceed 24 hours at a temperature of 2 °C to 8 °C, unless the solution is reconstituted in a place with controlled and validated aseptic conditions.Avoid allowing the reconstituted solution to reach room temperature.

Medications should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you do not need. In this way, you will help protect the environment.

Composition of Pemetrexed SUN

• The active ingredient is pemetrexed. Each vial contains 100, 500 or 1000 mg of pemetrexed (as pemetrexed disodium heptahydrate). After reconstitution, the solution contains 25 mg/ml of pemetrexed. Before administration, a healthcare professional is required to perform another dilution.
• The other components are mannitol, hydrochloric acid and/or sodium hydroxide (for pH adjustment) (for more information see section 2).

Appearance of the product and contents of the pack

Pemetrexed SUN is a lyophilized powder for concentrate for solution for infusion in a vial. It is a white to pale yellow or yellowish-green powder.

Each pack of Pemetrexed SUN contains a vial.

Holder of the marketing authorization and responsible manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

Local representative

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 Barcelona

Spain

Tel: +34 93 342 78 90

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorization holder.

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names

France:Pemetrexed SUN100 mg/500 mg/1000 mgpowder for solution for infusion

Germany:Pemetrexed SUN100 mg/500 mg/1000 mgPulverfor a concentratefor the preparation of an infusion solution

Italy:Pemetrexed SUN100 mg/500 mg/1000 mgpolvere per concentrato per soluzione per infusione

Netherlands:Pemetrexed SUN 100 mg/500 mg/1000 mg poeder voor concentraat voor oplossing voor infusie

Poland:Pemetreksed SUN100 mg/500 mg/1000 mgproszek do sporzadzania koncentratu roztworu do infuzji

Romania:Pemetrexed SUN100 mg/500 mg/1000 mgpulbere pentru concentrat pentru solutie perfuzabila

Spain:Pemetrexed SUN100 mgpowder for concentrate for solution for infusion EFG

Pemetrexed SUN500 mgpowder for concentrado for solution for infusion EFG

Pemetrexed SUN1000 mgpowder for concentrate for solution for infusion

Sweden:Pemetrexed SUN100 mg/500 mg/1000 mgpulver till koncentrat till infusionsvätska, lösning

United Kingdom (Northern Ireland):Pemetrexed SUN100 mg/500 mg/1000 mgpowder for concentrate for solution for infusion

Last revision date of this leaflet: January 2025

Further detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS): http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

Instructions for use, handling and disposal

1.Use aseptic techniques during the reconstitution and subsequent dilution of pemetrexed for its administration by intravenous infusion.

2.Calculate the dose and the number of vials of Pemetrexed SUN required. Each vial contains an excess of pemetrexed to facilitate the administration of the nominal required amount.

3.Pemetrexed SUN 100 mg:

Reconstitute each vial of 100 mg with 4.2 ml of a sodium chloride 9 mg/ml injection solution (0.9%), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed SUN 500 mg:

Reconstitute each vial of 500 mg with 20 ml of a sodium chloride 9 mg/ml injection solution (0.9%), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed SUN 1000 mg:

Reconstitute each vial of 1000 mg with 40 ml of a sodium chloride 9 mg/ml injection solution (0.9%), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Shake the vial thoroughly until the powder is completely dissolved. The resulting solution is transparent with a color range that may vary from colorless to yellow or yellowish-green without affecting the quality of the product. The pH of the reconstituted solution is between 6.6 and 7.8.Further dilution is required.

4.Dilute the appropriate volume of the reconstituted pemetrexed solution to 100 ml with a sodium chloride 9 mg/ml injection solution (0.9%) without preservatives, and administer as an intravenous infusion over 10 minutes.

5.The pemetrexed infusion solution prepared according to the above instructions 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.

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

1. Pemetrexed solutions are for single use. Dispose of the medication and unused material according to local requirements for cytotoxic medications.

Precautions in preparation and administration:

As with any other potentially toxic antineoplastic agent, special 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. 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 medications.