PEMETREXED SUN 500 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you receive Pemetrexed SUN

Do not use Pemetrexed SUN

• if you are allergic (hypersensitive) 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 SUN
• if you have recently received or are going to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with Pemetrexed SUN

• if you have had or have kidney problems, it may be that you cannot receive Pemetrexed SUN.

Before each infusion, you will need to provide blood samples to check 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 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 appropriate treatment before and after receiving cisplatin to prevent vomiting.

• if you have received or are going to receive radiotherapy, please consult your doctor, as an early or late reaction may occur between radiation and Pemetrexed SUN
• if you have been vaccinated recently, please consult your doctor, as this may cause some negative effect with Pemetrexed SUN
• if you have a heart condition 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 must not be used in children and adolescents, as there is no experience with this medicine in children and adolescents under 18 years of age.

Using Pemetrexed SUN with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription.

Please tell your doctor or pharmacist if you are taking

• pain or inflammation medicines (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (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 SUN infusion and/or the state of your kidney function, your doctor will advise you which medicines you can use and when you can take them. If you are not sure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

Tell 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 are planning to have a baby, ask your doctor for advice before taking 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 must use effective contraceptive methods during treatment with Pemetrexed SUN and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, tell your doctor. During treatment with Pemetrexed SUN, breastfeeding should be stopped.

Fertility

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

Driving and using machines

Pemetrexed SUN may make you feel tired. Be careful when driving a vehicle or using machines.

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/cooking salt) in each vial. This is equivalent to 2.7% of the maximum recommended daily intake of sodium for an adult.

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

3. How to use Pemetrexed SUN

The recommended dose of Pemetrexed SUN is 500 milligrams per square meter of your body surface area. Your height and weight will be measured 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 may be delayed depending on your blood cell count and your general 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 the Pemetrexed SUN infusion has finished. The cisplatin infusion lasts approximately two hours.

Normally, you should receive your infusion once every three weeks.

Additional medication:

• Corticosteroids: your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will need to take the day before, the day of, and the day after treatment with Pemetrexed SUN. Your doctor gives you this medicine 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 1000 micrograms) that you should take once a day while taking Pemetrexed SUN. You should take at least five doses during the seven days before the first dose of Pemetrexed SUN. You should continue taking folic acid during 21 days after the last dose of Pemetrexed SUN. You will also receive a vitamin B12 injection (1000 micrograms) in the week before administration of Pemetrexed SUN and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed SUN). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

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

4. Possible side effects

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

Serious side effects

Tell your doctor immediately if you notice any of the following serious side effects:

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

• pain, redness, swelling, or sores in the mouth
• allergic reaction: if you develop a rash. In rare cases, skin reactions can be serious and can cause death.
• low hemoglobin levels (anemia). You may feel tired or dizzy, if you are short of breath or 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 (as you may have a lower than normal white blood cell count, which is very common). Infections (sepsis) can be serious and can cause death.
• chest pain
• allergic reaction: burning or itching sensation and fever
• low platelet count. You may have bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising

Uncommon (may affect up to 1 in 100 people)

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

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

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

Other side effects

Tell 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
• pharyngitis (sore throat)
• low neutrophil count (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
• scaly skin
• changes in blood tests that show reduced kidney function
• fatigue (tiredness)

Common (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 reaction
• loss of body fluids
• altered sense of taste
• nerve damage that can cause muscle weakness or wasting (mainly in arms and legs)
• nerve damage that can cause loss of sensation, burning (severe burning), and unsteady gait
• dizziness
• inflammation or swelling of the conjunctiva (membrane that covers the eyelids and the white part of the eye)
• dry eyes
• tearful eyes
• dryness of the conjunctiva (membrane that covers the eyelids and the white part of the eye) and the cornea (transparent layer in front of the iris and pupil)
• swelling of the eyelids
• eye disorder with dryness, tearing, irritation, and/or pain
• heart failure (condition that affects the heart's pumping ability)
• irregular heartbeat
• indigestion
• constipation
• abdominal pain
• liver: increase in chemicals in the blood produced by the liver
• increased skin pigmentation
• itching of the skin
• skin rash that develops in a previously irradiated area
• hair loss
• hives
• kidney failure
• reduced kidney function
• fever
• pain
• excess fluid in the body tissue that causes swelling
• chest pain
• inflammation and ulceration of the mucous membranes that line the digestive tract

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 bleeding
• angina (chest pain caused by reduced blood flow to the heart)
• heart attack
• narrowing or blockage of the coronary arteries
• increased heart rate
• poor distribution of blood to the limbs
• obstruction in one of the pulmonary arteries in the lungs
• inflammation and scarring of the lung mucosa with respiratory problems
• loss of bright red blood through the anus
• bleeding in the gastrointestinal tract
• perforation of the intestine
• inflammation of the esophagus mucosa
• inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)
• inflammation, edema, erythema, and erosion of the mucous membrane surface of the esophagus caused by radiotherapy
• radiation-induced lung inflammation

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

• destruction of red blood cells
• anaphylactic shock (severe allergic reaction)
• inflammatory liver disease
• redness of the skin
• skin rash that develops in a previously irradiated area

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 that causes skin rashes and blisters on the legs, arms, and abdomen
• inflammation of the skin characterized by the presence of blisters that are filled with fluid
• skin fragility, blisters, and erosions and scarring of the skin
• redness, pain, and swelling mainly of the lower limbs
• inflammation of the skin and the fat under the skin (pseudocellulitis)
• skin inflammation (dermatitis)
• the skin becomes inflamed, itchy, red, cracked, and rough
• intensely itchy patches

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

• a type of diabetes derived mainly from kidney disease
• kidney disorder that involves the death of the epithelial tubular cells that form the renal tubules.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pemetrexed SUN

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

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

Do not use this medicine after the expiry date that appears on the vial or on the packaging after EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

After opening the vial, the medicine must be used immediately to avoid microbial contamination. If it is not used immediately, the storage time and 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 the reconstituted solution reaching room temperature.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Contents and Additional Information

Pemetrexed SUN Composition

• 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, it is required that the healthcare professional perform another dilution.
• The other components are mannitol, hydrochloric acid, and/or sodium hydroxide (for pH adjustment) (for more information, see section 2).

Product Appearance and Container Contents

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

Each container of Pemetrexed SUN contains one vial.

Marketing Authorization Holder and Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Netherlands

Local Representative

Sun Pharma Laboratories, S.L.

Rambla de Catalunya 53-55

08007 Barcelona

Spain

Tel: +34 93 342 78 90

More information about this medication can be requested from the local representative of the marketing authorization holder.

This medication is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names

France: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for solution to be diluted for infusion

Germany: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for concentrate for solution for infusion

Italy: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for concentrate for solution for infusion

Netherlands: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for concentrate for solution for infusion

Poland: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for solution for infusion

Romania: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for concentrate for solution for infusion

Spain: 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 1000 mg powder for concentrate for solution for infusion

Sweden: Pemetrexed SUN 100 mg/500 mg/1000 mg powder for concentrate for solution for infusion

United Kingdom: (Northern Ireland): Pemetrexed SUN 100 mg/500 mg/1000 mg powder for concentrate for solution for infusion

Date of the last revision of this prospectus: January 2025

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

Instructions for use, handling, and disposal

1. Use aseptic techniques during the reconstitution and subsequent dilution of pemetrexed for administration by intravenous infusion.
2. Calculate the dose and the number of Pemetrexed SUN vials needed. Each vial contains an excess of pemetrexed to facilitate the administration of the required nominal amount.
3. Pemetrexed SUN 100 mg:

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

Pemetrexed SUN 500 mg:

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

Pemetrexed SUN 1000 mg:

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

Shake the vial carefully 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 product quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

1. The appropriate volume of the reconstituted pemetrexed solution should be diluted to 100 ml with a 9 mg/ml (0.9%) sodium chloride injection solution without preservatives and administered as an intravenous infusion over 10 minutes.

1. 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 diluents containing calcium, including lactated Ringer's injection and Ringer's injection.

1. Parenteral medications should be visually inspected before administration to rule out the presence of particles or color alteration. If particles are observed, the medication should not be administered.

1. Pemetrexed solutions are for single use. The medication and unused material should be discarded 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. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be rinsed with plenty of water. Pemetrexed is not a vesicant drug. There is no specific antidote for pemetrexed extravasation. Some 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 other non-vesicant drugs.