Pemetrexed Sun 500 mg powder for concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: 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 the entire leaflet carefully before you start receiving this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Pemetrexed SUN is and what it is used for

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

• in combination with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a form of cancer affecting the lining of the lung, in patients who have not received prior chemotherapy.
• in combination with cisplatin, for the initial treatment of patients with advanced-stage lung cancer.
• for the treatment of patients with advanced-stage lung cancer whose disease has responded to treatment or whose disease has remained stable after initial chemotherapy.
• for the treatment of patients with advanced-stage lung cancer whose disease has progressed after having received prior chemotherapy.

2. What you need to know before starting Pemetrexed SUN

Do not use Pemetrexed SUN

• if you are allergic (hypersensitive) to pemetrexed or to 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 scheduled to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or pharmacist before starting Pemetrexed SUN

• if you have had or currently have kidney problems, you may not be able to receive Pemetrexed SUN.

Before each infusion, you will need to provide blood samples to check whether your kidney and liver function are adequate and to assess whether you have enough blood cells to receive Pemetrexed SUN. Your doctor may decide to adjust 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 you are properly hydrated and will give you 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 there may be an early or delayed interaction between radiation and Pemetrexed SUN.
• if you have been recently vaccinated, please consult your doctor, as the vaccine may potentially cause adverse effects with Pemetrexed SUN.
• if you have heart disease or a history of heart disease.
• if you have fluid buildup 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 individuals under 18 years of age.

Use of Pemetrexed SUN with other medicines

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

Please inform your doctor or hospital pharmacist if you are taking

• pain or anti-inflammatory (swelling) medicines, such as medicines known as “non-steroidal anti-inflammatory drugs” (NSAIDs), including those obtained 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 status, your doctor will advise you which medicines you can use and when. If you are unsure, consult your doctor or pharmacist to determine whether any medicine you are taking is an NSAID.

Inform your doctor if you are taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazol, and rabeprazol) used to treat stomach acid and acid reflux.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

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

Breastfeeding

If you are breastfeeding, inform your doctor. Breastfeeding must be discontinued during treatment with Pemetrexed SUN.

Fertility

Male patients are advised not to father a child during and for up to 6 months after treatment with Pemetrexed SUN, and should therefore use effective contraception during and for at least 3 months after treatment with Pemetrexed SUN. If you wish to father a child during treatment or within 3 months after treatment, seek advice from your doctor or pharmacist. Pemetrexed SUN may affect your ability to have children. Speak with your doctor for advice on sperm preservation before starting treatment.

Driving and use of machines

Pemetrexed SUN may make you feel tired. Be cautious when driving 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/cooking salt) per vial. This corresponds to 2.7% of the maximum daily recommended sodium intake for an adult.

Pemetrexed SUN 1000 mg contains approximately 108 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 5.4% of the maximum daily recommended sodium intake 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 value to determine the correct dose for you. This dose may be adjusted or the treatment may be delayed depending on your blood cell counts and your general condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed SUN powder with a sodium chloride injection solution of 9 mg/ml (0.9%), before administration.

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

When Pemetrexed SUN is used in combination with cisplatin:

• Your doctor or hospital pharmacist will calculate your required dose based on your height and weight. Cisplatin is also administered by intravenous infusion and is given approximately 30 minutes after the Pemetrexed SUN infusion has finished. The cisplatin infusion lasts approximately two hours.

You will normally receive your infusion once every three weeks.

Additional medication:

• Corticosteroids: Your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) to be taken the day before, the day of, and the day after your Pemetrexed SUN treatment. Your doctor prescribes this medication to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.

• Vitamin supplementation: Your doctor will prescribe oral folic acid (vitamin) or a multivitamin containing folic acid (350 to 1,000 micrograms) to be taken once daily while you are receiving Pemetrexed SUN. You should take at least five doses during the seven days prior to your first dose of Pemetrexed SUN. You must continue taking folic acid for 21 days after your last dose of Pemetrexed SUN. Additionally, you will receive an intramuscular injection of vitamin B12 (1,000 micrograms) during the week before your first Pemetrexed SUN administration, and then approximately every 9 weeks (corresponding to 3 treatment cycles of Pemetrexed SUN). Vitamin B12 and folic acid are given to reduce potential toxic effects of the cancer treatment.

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

4. Possible adverse effects

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

Serious adverse effects

Tell your doctor immediately if you notice any of the following serious adverse 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. Skin reactions are occasionally severe and may be fatal.
• low haemoglobin levels (anaemia). You may feel tired or dizzy, be short of breath, or look 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 fewer white blood cells than normal, which is very common). Infections (sepsis) can be severe and may cause death.
• chest pain
• allergic reaction: burning or itching sensation and fever
• low platelet count. You may have bleeding from 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)

• faster 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 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 adverse effects

Tell your doctor as soon as possible if you notice any of the following adverse effects:

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

• infection
• pharyngitis (sore throat)
• low neutrophil granulocyte count (a type of white blood cell)
• low white blood cell count
• low haemoglobin levels
• pain, redness, swelling, or sores in the mouth
• loss of appetite
• vomiting
• diarrhoea
• nausea
• skin rash
• scaly skin
• changes in blood tests showing reduced kidney function
• asthenia (weakness or tiredness)

Common (may affect up to 1 in 10 people)

• blood infection
• fever with low neutrophil granulocyte count (a type of white blood cell)
• low platelet count
• allergic reaction
• loss of body fluids
• altered sense of taste
• damage to motor nerves which may cause muscle weakness or atrophy (wasting, mainly in arms and legs)
• damage to sensory nerves which may cause loss of sensation, burning sensations (burning pain), and unsteady gait
• 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 inner membrane of the eyelids covering the white part of the eye) and cornea (transparent layer in front of the iris and pupil)
• eyelid swelling
• eye disorder with dryness, watering, irritation and/or pain
• heart failure (a condition affecting the pumping ability of the heart muscles)
• irregular heartbeat
• indigestion
• constipation
• abdominal pain
• liver: increased levels of chemicals in the blood produced by the liver
• increased skin pigmentation
• itchy skin
• rash on the body where each lesion resembles a target (bull's eye)
• hair loss
• urticaria
• kidney failure
• reduced kidney function
• fever
• pain
• excess fluid in body tissues causing swelling
• chest pain
• inflammation and ulceration of the mucous membranes lining 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
• ischaemia
• ischaemia due to blockage of a cerebral artery
• intracranial bleeding
• angina (chest pain caused by reduced blood flow to the heart)
• infarction
• narrowing or blockage of the coronary arteries
• increased heart rate
• poor blood distribution to the limbs
• obstruction in one of the pulmonary arteries in the lungs
• inflammation and scarring of the lung mucosa causing breathing problems
• bright red blood loss from the anus
• gastrointestinal tract bleeding
• intestinal perforation
• inflammation of the oesophageal mucosa
• inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only in combination with cisplatin)
• inflammation, oedema, erythema, and erosion of the mucosal surface of the oesophagus caused by radiotherapy
• lung inflammation caused by radiotherapy

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 developing 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 causing skin rashes and blisters on the legs, arms, and abdomen
• skin inflammation characterised by fluid-filled blisters
• skin fragility, blisters, erosions, and scarring of the skin
• redness, pain, and swelling mainly in the lower limbs
• inflammation of the skin and the fat beneath the skin (pseudocellulitis)
• skin inflammation (dermatitis)
• skin becomes inflamed, itchy, red, cracked, and rough
• intensely itchy spots

Frequency not known (cannot be estimated from available data)

• a type of diabetes primarily resulting from kidney disease
• kidney disorder involving death of tubular epithelial cells that form the renal tubules.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse 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 properly store Pemetrexed SUN.

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

Do not use this medicine after the expiry date stated on the vial or packaging after EXP. The expiry date refers to the last day of the month indicated.

This medicine requires no special storage conditions.

After opening the vial, the medicine should be used immediately to avoid microbial contamination. If not used immediately, the duration and conditions of storage 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 under controlled and validated aseptic conditions. Avoid allowing the reconstituted solution to reach room temperature.

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

6. Pack contents and other information

Composition of Pemetrexed SUN

• The active substance 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. Prior to administration, a further dilution must be performed by a healthcare professional.
• The other components are mannitol, hydrochloric acid and/or sodium hydroxide (for pH adjustment) (for further information see section 2).

Appearance of the medicinal product and contents of the pack

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

Each pack of Pemetrexed SUN contains one vial.

Marketing Authorization Holder and Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

The 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 is available from 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) under the following names

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

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

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

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

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

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

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 infusion solution

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

Date of the latest revision of this summary: January 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Instructions for use, handling and disposal

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

Reconstitute each 100 mg vial with 4.2 ml of sodium chloride 9 mg/ml (0.9%) solution for injection, preservative-free, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed SUN 500 mg:

Reconstitute each 500 mg vial with 20 ml of sodium chloride 9 mg/ml (0.9%) solution for injection, preservative-free, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed SUN 1000 mg:

Reconstitute each 1000 mg vial with 40 ml of sodium chloride 9 mg/ml (0.9%) solution for injection, preservative-free, to obtain a solution containing 25 mg/ml of pemetrexed.

Gently swirl the vial until the powder is completely dissolved. The resulting solution is clear, with a color range varying from colorless to yellow or greenish-yellow, without negatively affecting the product's quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

1. Dilute the appropriate volume of the reconstituted pemetrexed solution to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection, preservative-free, and administer as a 10-minute intravenous infusion.

2. The pemetrexed infusion solution prepared as described above is compatible with polyvinyl chloride and polyolefin infusion sets and bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer's injection and Ringer's injection.

3. Parenteral medicinal products should be visually inspected before administration for the presence of particulate matter or discoloration. If particles are observed, the medicinal product must not be administered.

4. Pemetrexed solutions are for single use only. Unused medicinal product and waste material must be disposed of in accordance with local requirements for cytotoxic drugs.

Precautions for 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, wash the affected area immediately and thoroughly with soap and water. If pemetrexed solutions come into contact with mucous membranes, rinse thoroughly with water. Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. Cases of pemetrexed extravasation have been reported, none of which were considered serious by the investigator. Extravasation should be managed according to standard clinical practice for non-vesicant drugs.