Pemetreksed sun

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Patient Information Leaflet

Pemetreksed SUN, 100 mg, powder for concentrate for solution for infusion
Pemetreksed SUN, 500 mg, powder for concentrate for solution for infusion
Pemetreksed SUN, 1000 mg, powder for concentrate for solution for infusion
Pemetrexedum
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

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

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

• in combination with another anticancer medicine, cisplatin, for the treatment of malignant pleural mesothelioma, a type of cancer affecting the lining of the lung, in patients who have not previously received chemotherapy;
• in combination with cisplatin, as first-line treatment in patients with advanced-stage non-small cell lung cancer;
• for the treatment of patients with advanced-stage non-small cell lung cancer who have achieved a response or whose disease remains largely stable after initial chemotherapy;
• for the treatment of patients with advanced-stage non-small cell lung cancer whose disease has progressed after initial treatment with other chemotherapeutic agents.

2. Important information before using Pemetreksed SUN

When not to use Pemetreksed SUN

• if the patient is allergic (hypersensitive) to pemetrexed or any of the other ingredients of this medicine (listed in section 6);
• if the patient is breastfeeding; breastfeeding must be discontinued during treatment with Pemetreksed SUN;
• in patients who have recently received or are due to receive the yellow fever vaccine.

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Warnings and precautions
Before starting treatment with Pemetreksed SUN, discuss the following with the doctor or hospital pharmacist:

• if the patient has or has previously had kidney function problems, as Pemetreksed SUN may not be suitable. Before each infusion, medical staff will take blood samples to assess whether liver and kidney function are sufficient and whether blood cell counts are adequate for treatment. Depending on the patient's overall condition and in case of a significant drop in blood cell counts, the doctor may adjust the dose or delay administration of the medicine. If the patient is also being treated with cisplatin, the doctor will check hydration status and recommend appropriate treatment to prevent vomiting.
• if the patient has undergone or will undergo radiotherapy, as early or delayed radiation reactions may occur after administration of Pemetreksed SUN;
• if the patient has recently received a vaccine, as this may cause adverse reactions when combined with Pemetreksed SUN;
• if the patient has or has had heart disease;
• if there is fluid accumulation around the lungs, the doctor may decide to perform a procedure to remove the fluid before administering Pemetreksed SUN.

Children and adolescents
Pemetreksed SUN must not be used in children and adolescents under 18 years of age, as there is no experience with use of this medicine in this age group.
Pemetreksed SUN and other medicines
Inform the doctor or hospital pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to use.
Inform the doctor or hospital pharmacist if the patient is taking:

• painkillers and anti-inflammatory medicines (e.g. those used to reduce swelling), such as non-steroidal anti-inflammatory drugs (NSAIDs), including those available without a prescription (e.g. 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 Pemetreksed SUN infusion and (or) the patient's kidney function, the doctor will advise which medicines can be taken and when. If in doubt whether a medicine belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs), ask the doctor or pharmacist.

Inform the doctor if the patient is taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lanzoprazole, pantoprazole and rabeprazole) used to treat heartburn and acid reflux.
Pregnancy, breastfeeding and fertility
Pregnancy
If the patient is pregnant, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine. Use of Pemetreksed SUN during pregnancy should be avoided. The doctor will inform the patient about the potential risks associated with using the medicine during pregnancy. Women must use an effective method of contraception during treatment with Pemetreksed SUN and for 6 months after receiving the last dose.
Breastfeeding
Women who are breastfeeding should inform their doctor. Breastfeeding must be discontinued during treatment with Pemetreksed SUN.
Fertility
Men are advised not to attempt to father a child during treatment and for 3 months after stopping Pemetreksed SUN, and to use effective contraception during this time.
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If a man intends to father a child while receiving Pemetreksed SUN or within 3 months after completion of treatment, he should seek advice from a doctor or pharmacist. Pemetreksed SUN may affect the ability to have children. Before starting treatment, patients should speak with their doctor for advice regarding sperm storage.
Driving and operating machinery
Pemetreksed SUN may cause fatigue. Caution should be exercised when driving or operating mechanical equipment.
Pemetreksed SUN contains sodium
Pemetreksed SUN 100 mg contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".
Pemetreksed SUN 500 mg contains approximately 54 mg of sodium (a major component of table salt) in each vial. This corresponds to 2.7% of the maximum recommended daily dietary sodium intake for adults.
Pemetreksed SUN 1000 mg contains approximately 108 mg of sodium (a major component of table salt) in each vial. This corresponds to 5.4% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Pemetreksed SUN

The recommended dose of Pemetreksed SUN is 500 milligrams per square metre
of the patient's body surface area. Body surface area is calculated based on measurements of the patient's height and weight.
The dose is determined according to body surface area. The dose may be adjusted or administration delayed, depending on the results of blood cell count tests and the patient's general condition.
Before administration, a pharmacist, nurse or doctor will reconstitute the powder with 9 mg/ml (0.9%) sodium chloride solution for injection.
Pemetreksed SUN is always administered as an intravenous infusion. The infusion lasts approximately 10 minutes.

Administration of Pemetreksed SUN in combination with cisplatin:

• The doctor or pharmacist will calculate the dose based on the patient's height and weight. Cisplatin is also administered as an intravenous infusion. The cisplatin infusion is started approximately 30 minutes after completion of the Pemetreksed SUN infusion and lasts about two hours.

The medicine will usually be given every 3 weeks.
Additional medicines:

• Corticosteroids: Your doctor will prescribe oral steroids (at a dose equivalent to 4 mg of dexamethasone twice daily), to be taken the day before, on the day of, and the day after administration of Pemetreksed SUN. These medicines are used to reduce the frequency and severity of skin reactions (skin changes) that may occur during administration of anticancer drugs.
• Vitamins: Your doctor will prescribe folic acid (a vitamin) or a multivitamin product containing folic acid (350–1000 micrograms), to be taken orally once daily during treatment with Pemetreksed SUN. At least five doses of folic acid should be taken during the seven days preceding the first dose of Pemetreksed SUN. Folic acid should be continued for 21 days after receiving the last dose of Pemetreksed SUN. In the week before administration of Pemetreksed SUN, and then at intervals of approximately 9 weeks (corresponding to three cycles of Pemetreksed SUN chemotherapy), patients will also receive vitamin B({12}) (1000 micrograms) by injection. Administration of vitamin B({12}) and folic acid aims to reduce the risk of adverse effects associated with anticancer drugs. If in doubt, consult your doctor, pharmacist or nurse.

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4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Serious adverse effects
Immediately inform your doctor if any of the following serious adverse effects occur:
Very common (may affect more than 1 in 10 people)

• pain, redness, swelling or sores in the mouth
• allergic reaction: skin rash. In rare cases, skin reactions may be severe and lead to death.
• low haemoglobin levels (anaemia). Symptoms may include feeling tired, weakness, shortness of breath or pale skin.

Common (may affect up to 1 in 10 people)

• fever or infection: if body temperature is 38°C or higher, excessive sweating or other signs of infection (due to possible excessive decrease in white blood cell count, which is very common). Infection (sepsis) may be severe and may lead to death.
• chest pain
• allergic reaction: burning or tingling sensation and fever
• reduced platelet count. May result in bleeding from gums, nose or mouth, or other uncontrolled bleeding, red or pink urine, or unexpected bruising on the skin.

Uncommon (may affect up to 1 in 100 people)

• increased heart rate
• blood clots in blood vessels of the lungs (pulmonary embolism). Symptoms may include sudden shortness of breath, severe chest pain, or coughing up blood-stained sputum.

Rare (may affect up to 1 in 1000 people)

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

Other adverse effects
Inform your doctor as soon as possible if any of the following adverse effects occur:
Very common (may affect more than 1 in 10 people)

• infection
• sore throat (throat pain)
• low neutrophil count (a type of white blood cells)
• low white blood cell count
• low haemoglobin levels
• pain, redness, swelling or mouth ulcers in the mouth
• loss of appetite
• vomiting
• diarrhoea
• nausea
• skin rash
• skin peeling
• abnormal blood test results indicating impaired kidney function
• fatigue

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Common (may affect up to 1 in 10 people)

• blood infection
• fever with low neutrophil count (a type of white blood cells)
• low platelet count
• allergic reaction
• fluid loss (dehydration)
• taste disturbances
• damage to motor nerves, which may cause weakness and muscle wasting in arms and legs
• damage to sensory nerves, which may cause loss of sensation, 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 membrane lining the eyelids and covering the white part of the eye) and cornea (the transparent layer covering the front of the iris and pupil)
• eyelid swelling
• eye disorders with associated dryness, watering, irritation and/or pain
• heart failure (a condition affecting the heart muscle's pumping ability)
• irregular heartbeat
• indigestion
• constipation
• abdominal pain
• liver: increased blood levels of chemicals produced by the liver
• increased skin pigmentation
• skin itching
• rash on the body with lesions resembling target lesions
• hair loss
• hives
• kidney shutdown
• worsening kidney function
• fever
• pain
• excess fluid in body tissues causing swelling
• chest pain
• inflammation and ulceration of the mucous membranes lining the gastrointestinal tract

Uncommon (may affect up to 1 in 100 people)

• decreased number of red blood cells, white blood cells and platelets
• stroke
• a type of stroke caused by blockage of an artery supplying blood to the brain
• intracranial haemorrhage
• angina pectoris (chest pain caused by reduced blood flow to the heart)
• heart attack
• narrowing or blockage of coronary arteries
• increased heart rate
• insufficient blood flow to limbs
• blockage of one of the pulmonary arteries
• inflammatory condition and scarring of the membrane lining the lungs, with breathing difficulties
• bright red rectal bleeding
• gastrointestinal bleeding
• intestinal wall rupture
• oesophagitis (inflammation of the oesophageal mucosa)
• inflammation of the mucous membrane of the large intestine, which may be accompanied by intestinal and rectal bleeding (observed only when used in combination with cisplatin)

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• inflammation, swelling, redness and ulceration of the oesophageal mucosa caused by radiotherapy
• radiation-induced pneumonitis (lung inflammation caused by radiotherapy)

Rare (may affect up to 1 in 1000 people)

• haemolysis (breakdown of red blood cells)
• anaphylactic shock (severe allergic reaction)
• inflammatory liver disease
• skin redness
• skin rash developing in areas previously exposed to radiation

Very rare (may affect no more than 1 in 10,000 people)

• skin and soft tissue infections
• Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction, which may be life-threatening)
• toxic epidermal necrolysis (a type of severe skin reaction, which may be life-threatening)
• autoimmune disorders causing rash and blistering on the skin of legs, arms and abdomen
• skin inflammation with presence of fluid-filled blisters
• fragile skin, presence of blisters, erosions and skin scarring
• redness, pain and swelling, mainly in the lower limbs
• inflammation of the skin and subcutaneous fat tissue
• skin inflammation
• inflammatory condition, itching, redness, cracking and roughness of the skin
• intensely itchy skin lesions

Frequency not known (cannot be estimated from available data)

• a type of diabetes caused mainly by abnormal kidney changes
• kidney disorders leading to necrosis of tubular epithelial cells.

Reporting of adverse effects
If any adverse symptoms occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl. Adverse effects can also be reported to the marketing authorisation holder. Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Pemetreksed SUN

Your doctor, pharmacist or nurse knows how to store Pemetreksed SUN.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
There are no special storage instructions for this medicine.
The medicine should be administered immediately after opening the vial to avoid microbiological contamination.
If the medicine is not used immediately after opening, the person administering the medicine is responsible for ensuring correct storage conditions and duration, which should not exceed 24 hours at 2°C – 8°C, unless the solution was prepared under controlled and validated aseptic conditions. If the medicine has been stored in a refrigerator, allow it to reach room temperature before administration.

6. Contents of the pack and other information

What Pemetreksed SUN contains

• The active substance in this medicine is pemetrexed. Each vial contains 100, 500 or 1000 milligrams of pemetrexed (as pemetrexed disodium heptahydrate). The reconstituted solution contains 25 mg/ml of pemetrexed. Before administration, the medicine must be further diluted. This will be performed by healthcare professionals.
• Other ingredients are: mannitol, hydrochloric acid and (or) sodium hydroxide (for pH adjustment) (further information is provided in section 2).

What Pemetreksed SUN looks like and contents of the pack
The medicine is a powder for solution for infusion concentrate. It is a lyophilised powder, white to slightly yellow or greenish-yellow in colour.
Each pack contains one vial.

Marketing Authorisation Holder
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

Manufacturer/Importer
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

This medicine is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
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
The Netherlands: Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg powder for concentrate for solution for infusion
Poland: Pemetreksed SUN
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 perfusion EFG
Pemetrexed SUN 500 mg powder for concentrate for solution for perfusion EFG
Pemetrexed SUN 1000 mg powder for concentrate for solution for perfusion
United Kingdom (Northern Ireland): Pemetrexed SUN 100 mg/ 500 mg/ 1000 mg powder for concentrate for solution for infusion
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The following information is intended exclusively for medical professionals or

healthcare personnel
Instructions for preparation, administration, and disposal of the medicinal product.

1. Preparation of pemetrexed solution and further dilution for intravenous infusion must be carried out under aseptic conditions.
2. Calculate the required dose and number of vials of Pemetreksed SUN needed. Each vial contains slightly more drug than indicated on the label, which facilitates withdrawal of the labeled volume.
3. Pemetreksed SUN 100 mg:
   Reconstitute the contents of the 100 mg vial with 4.2 mL of sodium chloride injection solution at a concentration of 9 mg/mL (0.9%), free from preservatives. The resulting solution contains 25 mg/mL of pemetrexed.

Pemetreksed SUN 500 mg:
Reconstitute the contents of the 500 mg vial with 20 mL of sodium chloride injection solution at a concentration of 9 mg/mL (0.9%), free from preservatives. The resulting solution contains 25 mg/mL of pemetrexed.
Pemetreksed SUN 1000 mg:
Reconstitute the contents of the 1000 mg vial with 40 mL of sodium chloride injection solution at a concentration of 9 mg/mL (0.9%), free from preservatives. The resulting solution contains 25 mg/mL of pemetrexed.
Gently rotate each vial until the powder is completely dissolved.
The resulting solution is clear, colorless to yellow or yellow-green in color (color does not affect product quality). The pH of the reconstituted solution ranges from 6.6 to 7.8. Osmolality of the solution ranges from 480 to 570 mOsm/kg. The solution must be further diluted.

4. The appropriate volume of the prepared pemetrexed solution should be further diluted to a final volume of 100 mL using sodium chloride injection solution at a concentration of 9 mg/mL (0.9%), free from preservatives. The medicinal product should be administered as an intravenous infusion over 10 minutes.
5. Pemetrexed infusion solutions prepared as described above have shown no incompatibilities with infusion bags and administration sets whose inner layer is made of polyvinyl chloride and polyolefin. Pemetrexed exhibits physical incompatibility with diluents containing calcium, including Ringer's injection solution with lactate and Ringer's injection solution.
6. Prior to parenteral administration, visually inspect the solution for particulate matter and discoloration. If visible particulates are present in the solution, the medicinal product must not be administered.
7. The pemetrexed solution is intended for single use only. Any unused medicinal product or waste material must be disposed of in accordance with applicable regulations for cytotoxic drugs.

Precautions during preparation and administration of the medicinal product.
As with other potentially toxic antineoplastic agents, caution should be exercised when handling and preparing pemetrexed solutions for infusion. The use of gloves is recommended. In case of contact of the pemetrexed solution with the skin, wash the skin immediately and thoroughly with soap and water. In case of contact with mucous membranes, flush the affected area thoroughly with water. Pemetrexed does not cause blistering. There is no known specific antidote in the event of extravasation of pemetrexed. There have been rare reports of extravasation of the drug, which were not assessed by investigators as serious. In case of extravasation, manage according to standard practice for other non-vesicant substances.