Pemetrexed Pfizer

Patient Information Leaflet: Information for the User

Pemetrexed Pfizer 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion, 1,000 mg powder for concentrate for solution for infusion

pemetrexed
Please read this leaflet carefully before you are given this medicine because it contains
important information for you.

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

Contents of this leaflet

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

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

Pemetrexed Pfizer is a medicine used in the treatment of cancers.
Pemetrexed Pfizer is administered in combination with cisplatin, another anticancer medicine,
as treatment for malignant pleural mesothelioma, a type of cancer affecting the lining of the lungs,
in patients who have not received prior chemotherapy.
Additionally, Pemetrexed Pfizer, in combination with cisplatin, is used as first-line therapy in patients with advanced-stage lung cancer.
Pemetrexed Pfizer may be prescribed for advanced-stage lung cancer if the disease has responded to treatment or remains largely unchanged after initial chemotherapy.
Furthermore, Pemetrexed Pfizer is a treatment for patients with advanced-stage lung cancer whose disease has progressed after prior initial chemotherapy treatment.

2. What you need to know before taking Pemetrexed Pfizer

Do not use Pemetrexed Pfizer:

• 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 Pfizer.
• if you have recently received or are about to receive the yellow fever vaccine.

Warnings and precautions:
Talk to your doctor or hospital pharmacist before receiving Pemetrexed Pfizer.
If you have or have had kidney problems, inform your doctor or hospital pharmacist, as you may not be able to receive Pemetrexed Pfizer.
Before each infusion, blood tests will be performed to assess whether you have adequate liver and kidney function and to check that you have enough blood cells to receive Pemetrexed Pfizer. Your doctor may decide to adjust the dose or delay treatment depending on your general condition and if blood tests (white blood cells and platelets) show inadequate levels (too low). Additionally, if you are receiving cisplatin, your doctor must ensure that you are adequately hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting.
If you have undergone or will undergo radiation therapy, inform your doctor, as you may experience an early or delayed reaction due to radiation treatment when using Pemetrexed Pfizer.
If you have recently been vaccinated, inform your doctor, as this could cause harmful effects when using Pemetrexed Pfizer.
If you have heart disease or a history of heart disease, inform your doctor.
If you have fluid accumulation around the lungs, your doctor may decide to drain the fluid before administering Pemetrexed Pfizer.

Children and adolescents
This medicine must not be used in children and adolescents, as there is no experience with use in individuals under 18 years of age.

Other medicines and Pemetrexed Pfizer
Inform your doctor if you are taking any medicine for pain or inflammation (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (NSAIDs), including medicines purchased without a prescription (such as ibuprofen). There are many types of NSAIDs with different durations of action. Depending on the scheduled date for pemetrexed infusion and/or your kidney function, your doctor will advise you which medicines you can take and when you can take them. If you are unsure, ask your doctor or pharmacist whether any of your medicines are NSAIDs.
Inform your doctor or hospital pharmacist if you are taking or have recently taken any other medicines, including those without a prescription.

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, inform your doctor. The use of pemetrexed during pregnancy should be avoided. Your doctor will discuss with you the potential risks of taking pemetrexed during pregnancy. Women must use an effective method of contraception during treatment with pemetrexed and for 6 months after receiving the last dose.

Breastfeeding
If you are breastfeeding, inform your doctor. Breastfeeding must be stopped during treatment with pemetrexed.

Fertility
Men are advised not to father a child during treatment with pemetrexed and for 3 months after treatment ends, and should therefore use an effective contraceptive method during treatment with pemetrexed and for 3 months afterwards. If you wish to father a child during treatment or within 3 months after, consult your doctor or pharmacist. Pemetrexed Pfizer may affect your ability to have children. Speak with your doctor for advice on sperm preservation before starting therapy.

Driving and using machines
Pemetrexed Pfizer may cause tiredness. Be cautious when driving a vehicle or operating machinery.

Pemetrexed Pfizer contains sodium
Pemetrexed Pfizer 100 mg powder for concentrate for solution for infusion
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is essentially "sodium-free".
Pemetrexed Pfizer 500 mg powder for concentrate for solution for infusion
This medicine contains 54 mg of sodium (the main component of table salt) per vial. This corresponds to 2.7% of the maximum daily recommended dietary intake for an adult.
Pemetrexed Pfizer 1.000 mg powder for concentrate for solution for infusion
This medicine contains 108 mg of sodium (the main component of table salt) per vial. This corresponds to 5.4% of the maximum daily recommended dietary intake for an adult.

3. How to take Pemetrexed Pfizer

The dose of Pemetrexed Pfizer is 500 mg per square metre of body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this body surface area to determine the correct dose for you. This dosage may be adjusted or the treatment may be delayed depending on your blood test results and your general condition. A hospital pharmacist, nurse, or doctor will have reconstituted the Pemetrexed Pfizer powder with a 9 mg/ml (0.9%) sodium chloride solution for injectable preparations before administering it to you.
You will always receive Pemetrexed Pfizer by intravenous infusion. The infusion will last approximately 10 minutes.
When Pemetrexed Pfizer is used in combination with cisplatin:
Your doctor or hospital pharmacist will calculate the dose you require based on your height and weight. Cisplatin is also administered by intravenous infusion, approximately 30 minutes after the Pemetrexed Pfizer infusion has been completed. The cisplatin infusion will last about 2 hours.
Typically, you should receive the infusion once every 3 weeks.
Additional medicines:
Corticosteroids: Your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) to be taken the day before, on the day of, and the day after treatment with Pemetrexed Pfizer. This medicine is given to reduce the frequency and severity of skin reactions that may occur during anticancer treatment.
Vitamin supplement: Your doctor will prescribe folic acid (vitamin) or a multivitamin product containing folic acid (350–1,000 micrograms) to be taken orally once daily during treatment with Pemetrexed Pfizer.
You must take at least 5 doses during the 7 days prior to the first dose of Pemetrexed Pfizer.
You must continue taking folic acid for 21 days after the last dose of Pemetrexed Pfizer.
You will also receive an injection of vitamin B₁₂ (1,000 micrograms) during the week before administration of Pemetrexed Pfizer, and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Pfizer). Vitamin B₁₂ and folic acid are administered to reduce the potential toxic effects of anticancer treatment.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You must contact your doctor immediately if you notice any of the following side effects:

• Fever or infection (respectively common or very common): if you have a body temperature of 38 °C or higher, sweating, or other signs of infection (because you may have fewer white blood cells than normal, which is very common). Infection (sepsis) can be severe and may lead to death.
• If you start experiencing chest pain (common) or an increased heart rate (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), burning or tingling sensation (common), or fever (common). Rarely, skin reactions can be severe and may lead to death. Contact your doctor if a severe rash appears, or if you experience itching or blisters form (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired, faint, short of breath, or look pale (because you may have lower than normal haemoglobin levels, which is very common).
• If you have bleeding from the gums, nose, or mouth, or any bleeding that does not stop easily, red or slightly pink urine, or unexpected bruising (because you may have fewer platelets than normal, which is common).
• If you suddenly experience shortness of breath, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the blood vessels of the lungs).

Side effects with pemetrexed may include:
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 ulcers in the mouth
Loss of appetite
Vomiting
Diarrhoea
Nausea
Skin redness
Skin peeling
Abnormal blood tests showing reduced kidney function
Fatigue (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 reactions
Loss of body fluids
Altered taste
Nerve damage that may cause stiffness and muscle atrophy, leading to muscle weakness and primary atrophy in arms and legs
Sensory nerve damage that may cause loss of sensation, burning sensations, 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
Excessive tearing
Dryness of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye) and cornea (the transparent layer in front of the iris and pupil)
Swollen eyelids
Eye disorders with dryness, tearing, 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
Widespread red spots
Hair loss
Hives
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

Uncommon (may affect up to 1 in 100 people)
Reduction in the number of white and red blood cells and platelets in the blood
Stroke
Type of stroke when a brain artery is blocked
Bleeding in the skull
Angina (chest pain caused by reduced blood flow to the heart)
Heart attack
Narrowing or blockage of the coronary arteries
Increased heart rate
Poor blood circulation to the limbs
Blockage in the lungs of one of the pulmonary arteries
Inflammation and scarring of the lung lining with breathing problems
Bleeding bright red blood from the anus
Gastrointestinal tract bleeding
Intestinal rupture
Inflammation of the oesophageal lining
Inflammation of the lining of the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only in combination with cisplatin)
Inflammation, swelling, redness, and erosion of the oesophageal mucosal surface caused by radiation therapy
Lung inflammation caused by radiation therapy

Rare (may affect up to 1 in 1,000 people)
Destruction of red blood cells
Anaphylactic shock (severe allergic reaction)
Inflammatory liver condition
Skin redness
Sudden skin redness developing in a previously irradiated area

Very rare (may affect up to 1 in 10,000 people)
Skin and soft tissue infection
Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that could be life-threatening)
Toxic epidermal necrolysis (a type of severe skin reaction that could be life-threatening)
Autoimmune disorders resulting in sudden skin redness and blisters on the legs, arms, and abdomen
Skin inflammation characterized by fluid-filled blisters
Skin fragility, blistering, erosion, and scarring
Redness, pain, and swelling, mainly in the lower limbs
Inflammation of the skin and underlying fat (pseudocellulitis)
Skin inflammation (dermatitis)
Skin becoming inflamed, itchy, red, cracked, and rough
Intensely itchy spots

Not known: frequency cannot be estimated from the available data
A form of diabetes primarily due to kidney disease
Kidney disorders leading to death of tubular epithelial cells forming the kidney tubules

You may experience one or more of these symptoms and/or conditions. You must inform your doctor as soon as possible when you start experiencing any of these side effects.
If you have any questions about any side effect, talk to your doctor.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pemetrexed Pfizer

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer packaging and on the vial label following the abbreviation "Exp". The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Reconstituted and infusion solutions: the medicine should be used immediately. If prepared as directed, chemical and physical in-use stability of reconstituted pemetrexed solutions for infusion has been demonstrated for 24 hours when stored refrigerated (between 2°C and 8°C).
The reconstituted solution is clear and may vary from colourless to yellow or yellow-green, which does not negatively affect the quality of the product. Before administration, parenteral medicinal products should be inspected visually for the presence of particles and discoloration.
Do not administer if particles are observed.
This medicine is for single use only; any unused solution must be disposed of in accordance with local legal requirements.

6. Package contents and other information

What Pemetrexed Pfizer contains
The active substance is pemetrexed.
Pemetrexed Pfizer 100 mg powder for concentrate for solution for infusion: Each vial contains 100 milligrams of pemetrexed (as pemetrexed disodium hemipentahydrate).
Pemetrexed Pfizer 500 mg powder for concentrate for solution for infusion: Each vial contains 500 milligrams of pemetrexed (as pemetrexed disodium hemipentahydrate).
Pemetrexed Pfizer 1.000 mg powder for concentrate for solution for infusion: Each vial contains 1.000 milligrams of pemetrexed (as pemetrexed disodium hemipentahydrate).
After reconstitution, the solution contains 25 mg/ml of pemetrexed. Further dilution by healthcare professionals is required prior to administration.
The other components are mannitol (E421), hydrochloric acid (to adjust pH) and sodium hydroxide (to adjust pH). See section 2 “Pemetrexed Pfizer contains sodium”.

Description of the appearance of Pemetrexed Pfizer and contents of the pack
Pemetrexed Pfizer is a powder for concentrate for solution for infusion in a glass vial. It is a lyophilized powder with a colour ranging from white to pale yellow or yellow-green.
Each pack contains one vial of 100 mg, 500 mg or 1.000 mg of pemetrexed as pemetrexed disodium hemipentahydrate.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Pfizer Service Company BV
Hoge Wei 10
1930 Zaventem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

BE LT
Pfizer SA/NV Pfizer Luxembourg SARL filialas Lietuvoje
Tél/Tel: +32 2 554 62 11 Tel. + 370 52 51 4000

BG LU
Пфайзер Люксембург САРЛ, Клон България Pfizer SA/NV
Тел.: +359 2 970 4333 Tél/Tel: +32 2 554 62 11

CZ HU
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: + 36 1 488 37 00

DK MT
Pfizer ApS Drugsales Ltd
Tlf: + 45 44 20 11 00 Tel.: + 356 21 419 070/1/2

DE NL
PFIZER PHARMA GmbH Pfizer bv
Tel: + 49 (0) 30 550055-51000 Tel: +31 (0) 800 63 34 636

EE NO
Pfizer Luxembourg SARL Eesti filiaal Pfizer AS
Tel: +372 666 7500 Tlf: +47 67 52 61 00

EL AT
Pfizer ΕΛΛΑΣ A.E. Pfizer Corporation Austria Ges.m.b.H.
Τηλ.: +30 210 6785 800 Tel: +43 (0)1 521 15-0

ES PL
Pfizer, S.L. Pfizer Polska Sp. z o.o.
Tel: +34 91 490 99 00 Tel: +48 22 335 61 00

FR PT
Pfizer Laboratórios Pfizer, Lda.
Tél: + 33 (0)1 58 07 34 40 Tel: + 351 21 423 55 00

HR RO
Pfizer Croatia d.o.o. Pfizer România S.R.L.
Tel: +385 1 3908 777 Tel: +40 (0)21 207 28 00

IE SI
Pfizer Healthcare Ireland Pfizer Luxembourg SARL
Tel: 1800 633 363 (toll free) Pfizer, podružnica za svetovanje s področja
+44 (0) 1304 616161 farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IS SK
Icepharma hf. Pfizer Luxembourg SARL, organizačná zložka
Sími: +354 540 8000 Tel: +421–2–3355 5500

IT FI
Pfizer S.r.l. Pfizer Oy
Tel: +39 06 33 18 21 Puh/Tel: +358 (0)9 430 040

CY SE
Pfizer Ελλάς Α.Ε. (Cyprus Branch) Pfizer AB
Τηλ.: +357 22817690 Tel: +46 (0)8 550 520 00

LV UK (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel.: + 371 670 35 775 Tel: + 44 (0) 1304 616161

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu
This leaflet is available in all EU/EEA languages on the website of the European Medicines Agency.

The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling, and disposal

1. During reconstitution and further dilution of pemetrexed for intravenous infusion administration, use aseptic techniques.
2. Calculate the required dose and the number of vials of Pemetrexed Pfizer needed. Each vial contains an overage of pemetrexed to facilitate delivery of the amount stated on the label.
3. Reconstitute each 100 mg vial with 4.2 ml of sodium chloride solution 9 mg/ml (0.9 %) for injectable preparations, without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Reconstitute each 500 mg vial with 20 ml of sodium chloride solution 9 mg/ml (0.9 %) for injectable preparations, without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.
Reconstitute each 1,000 mg vial with 40 ml of sodium chloride solution 9 mg/ml (0.9 %) for injectable preparations, without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.
Gently shake each vial until the powder is completely dissolved. The resulting solution is clear and may vary from colourless to yellow or yellow-green without negatively affecting the quality of the product. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

4. The appropriate volume of reconstituted pemetrexed solution must be further diluted to 100 ml with sodium chloride solution 9 mg/ml (0.9 %) for injectable preparations, without preservatives, and administered as a 10-minute intravenous infusion.
5. Infusion solutions of pemetrexed prepared as described above are compatible with infusion bags and administration sets coated with polyvinyl chloride and polyolefins. Pemetrexed is incompatible with diluents containing calcium, including sodium chloride and potassium chloride with glucose 4% and 0.18% for infusion and Ringer's lactate solution for injectable preparations.
6. Parenteral medicinal products should be inspected visually for particulate matter and changes in colour prior to administration. Do not administer if particulate matter is observed.
7. Pemetrexed solutions are for single use only. Unused medicine and waste materials resulting from this medicine must be disposed of in accordance with local legal requirements.

Precautions for preparation and administration: As with other potentially toxic antineoplastic agents, caution should be exercised when handling and preparing pemetrexed infusion solutions. The use of gloves is recommended. If a pemetrexed solution comes into contact with the skin, wash 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 and were not considered severe by the investigator. Extravasation should be managed according to standard procedures for non-vesicant agents.

Package leaflet: Information for the user

Pemetrexed Pfizer 25 mg/ml concentrate for solution for infusion

pemetrexed
Please read this leaflet carefully before receiving this medicine because it contains
important information for you.

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

Contents of this leaflet

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

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

Pemetrexed Pfizer is a medicine used to treat cancers.
Pemetrexed Pfizer is given in combination with cisplatin, another anticancer medicine,
as treatment for malignant pleural mesothelioma, a type of cancer affecting the lining of the lungs, in patients who have not previously received chemotherapy.
Additionally, Pemetrexed Pfizer, in combination with cisplatin, is used as first-line therapy in patients with advanced-stage lung cancer.
Pemetrexed Pfizer may be prescribed for advanced-stage lung cancer if the disease has responded to treatment or remains mostly unchanged after initial chemotherapy.
Furthermore, Pemetrexed Pfizer is a treatment for patients with advanced-stage lung cancer whose disease has progressed after prior initial chemotherapy treatment.

2. What you should know before taking Pemetrexed Pfizer

Do not use Pemetrexed Pfizer:

• 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 Pfizer.
• if you have recently received or are about to receive the yellow fever vaccine.

Warnings and precautions:
Talk to your doctor or hospital pharmacist before receiving Pemetrexed Pfizer.
If you have or have had kidney problems, inform your doctor or hospital pharmacist, as you may not be able to receive Pemetrexed Pfizer.
Before each infusion, blood tests will be performed to assess whether you have adequate liver and kidney function and to check that you have enough blood cells to receive Pemetrexed Pfizer. Your doctor may decide to adjust the dose or delay treatment depending on your general condition and if blood test results (white blood cells and platelets) are inadequate (too low). Additionally, if you are receiving cisplatin, your doctor must ensure that you are adequately hydrated and that you receive appropriate treatment before and after receiving cisplatin to prevent vomiting.
If you have undergone or are scheduled to undergo radiation therapy, inform your doctor, as you may experience an early or delayed reaction due to radiation when receiving Pemetrexed Pfizer.
If you have recently been vaccinated, inform your doctor, as Pemetrexed Pfizer could cause harmful effects.
If you have heart disease or a history of heart disease, inform your doctor.
If you have fluid accumulation around the lungs, your doctor may decide to drain the fluid before administering Pemetrexed Pfizer.

Children and adolescents
This medicine must not be used in children and adolescents, as there is no experience with use in individuals under 18 years of age.

Other medicines and Pemetrexed Pfizer
Inform your doctor if you are taking any medicine for pain or inflammation (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (NSAIDs), including medicines purchased without a prescription (such as ibuprofen). There are many types of NSAIDs with different durations of action. Depending on the scheduled date for pemetrexed infusion and/or your kidney function, your doctor will advise you on which medicines you can take and when you can take them. If you are unsure, ask your doctor or pharmacist whether any of your medicines are NSAIDs.
Inform your doctor or hospital pharmacist if you are taking or have recently taken any other medicines, including those without a prescription.

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, inform your doctor. The use of pemetrexed during pregnancy should be avoided. Your doctor will discuss with you the potential risks of taking pemetrexed during pregnancy. Women must use an effective method of contraception during treatment with pemetrexed and for 6 months after receiving the last dose.

Breastfeeding
If you are breastfeeding, inform your doctor. Breastfeeding must be stopped during treatment with pemetrexed.

Fertility
Men are advised not to father a child during treatment with pemetrexed and for up to 3 months afterwards, and should therefore use an effective contraceptive method during treatment with pemetrexed and for up to 3 months afterwards. If you wish to father a child during treatment or within 3 months afterwards, consult your doctor or pharmacist. Pemetrexed Pfizer may affect your ability to have children. Speak with your doctor for advice on sperm preservation before starting therapy.

Driving and using machines
Pemetrexed Pfizer may cause fatigue. Be cautious when driving a vehicle or operating machinery.

Pemetrexed Pfizer contains sodium
Each 4 ml vial contains less than 1 mmol of sodium (23 mg), i.e., it is essentially "sodium-free".
Each 20 ml vial contains 54 mg of sodium (the main component of table salt). This corresponds to 2.7% of the maximum recommended daily dietary intake for an adult.
Each 40 ml vial contains 108 mg of sodium (the main component of table salt). This corresponds to 5.4% of the maximum recommended daily dietary intake for an adult.

3. How to take Pemetrexed Pfizer

The dose of Pemetrexed Pfizer is 500 mg per square metre of body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this body surface area to determine the correct dose for you. This dosage may be adjusted or the treatment may be delayed depending on blood test results and your general condition. A hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Pfizer concentrate with a sodium chloride solution 9 mg/mL (0.9%) for injectable preparations before administering it to you. Pemetrexed Pfizer will always be given by intravenous infusion. The infusion will last approximately 10 minutes.

When Pemetrexed Pfizer is used in combination with cisplatin:
Your doctor or hospital pharmacist will calculate the dose you require based on your height and weight. Cisplatin is also administered by intravenous infusion, approximately 30 minutes after completion of the Pemetrexed Pfizer infusion. The cisplatin infusion will last about 2 hours.
Typically, you will receive the infusion once every 3 weeks.

Additional medicines:
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 treatment with Pemetrexed Pfizer. This medicine is given to reduce the frequency and severity of skin reactions that may occur during anticancer treatment.

Vitamin supplement: Your doctor will prescribe folic acid (vitamin) or a multivitamin product containing folic acid (350–1,000 micrograms) to be taken orally once daily during treatment with Pemetrexed Pfizer.
You must take at least five doses during the seven days before the first dose of Pemetrexed Pfizer. You should continue taking folic acid for 21 days after the last dose of Pemetrexed Pfizer.

You will also receive an injection of vitamin B({12}) (1,000 micrograms) during the week before administration of Pemetrexed Pfizer, and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Pfizer). Vitamin B({12}) and folic acid are administered to reduce the potential toxic effects of anticancer treatment.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You must contact your doctor immediately if you notice any of the following side effects:

• Fever or infection (respectively common or very common): if you have a body 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). The infection (sepsis) can be severe and may lead to death.
• If you start experiencing chest pain (common) or an increased heart rate (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), burning or tingling sensation (common), or fever (common). Rarely, skin reactions can be severe and may lead to death. Contact your doctor if a severe rash appears, or if you experience itching or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired, faint, become short of breath easily, or appear pale (as you may have lower than normal haemoglobin levels, which is very common).
• If you have bleeding from the gums, nose, or mouth, or any bleeding that does not tend to stop, reddish or slightly pink urine, or unexpected bruising (as you may have fewer platelets than normal, which is common).
• If you experience sudden shortness of breath, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the blood vessels of the lungs).

Side effects with pemetrexed may include:
Very common (may affect more than 1 in 10 people)
Infection
Pharyngitis (sore throat)
Low neutrophil granulocyte count (a type of white blood cell in the blood)
Low white blood cell count
Low haemoglobin levels
Pain, redness, swelling, or ulcers in the mouth
Loss of appetite
Vomiting
Diarrhoea
Nausea
Skin redness
Skin peeling
Abnormal blood tests showing reduced kidney function
Fatigue (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 reactions
Loss of body fluids
Altered taste
Damage to motor nerves which may cause stiffness and muscle atrophy, leading to muscle weakness and primary atrophy in the arms and legs
Damage to sensory nerves which may cause loss of sensation, burning sensations, 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
Excessive tearing
Dryness of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye) and the cornea (the transparent layer in front of the iris and pupil)
Swollen eyelids
Eye disorders with dryness, tearing, irritation, and/or pain
Heart failure (a condition affecting the heart muscle's pumping ability)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increased levels in blood of chemicals produced by the liver
Increased skin pigmentation
Skin itching
Widespread red spots
Hair loss
Hives
Kidneys stop working
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

Uncommon (may affect up to 1 in 100 people)
Reduction in the number of white and red blood cells and platelets in the blood
Stroke
Type of stroke when an artery in the brain is blocked
Bleeding in the skull
Angina (chest pain caused by reduced blood flow to the heart)
Heart attack
Narrowing or blockage of the coronary arteries
Increased heart rate
Inadequate blood supply to the limbs
Blockage in the lungs, affecting one of the pulmonary arteries
Inflammation and scarring of the lung lining causing breathing problems
Bright red bleeding from the anus
Gastrointestinal tract bleeding
Intestinal perforation
Inflammation of the oesophageal lining
Inflammation of the lining 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 radiation therapy
Lung inflammation caused by radiation therapy

Rare (may affect up to 1 in 1,000 people)
Destruction of red blood cells
Anaphylactic shock (severe allergic reaction)
Inflammatory condition of the liver
Skin redness
Sudden skin redness developing in an area previously irradiated

Very rare (may affect up to 1 in 10,000 people)
Skin and soft tissue infection
Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that could be life-threatening)
Toxic epidermal necrolysis (a type of severe skin reaction that could be life-threatening)
Autoimmune disorders resulting in sudden skin flushing and blisters on the legs, arms, and abdomen
Skin inflammation characterized by the presence of fluid-filled blisters
Skin fragility, blistering, erosion, and scarring
Redness, pain, and swelling, mainly in the lower limbs
Inflammation of the skin and subcutaneous fat (pseudocellulitis)
Skin inflammation (dermatitis)
Skin becoming inflamed, itchy, red, cracked, and rough
Intensely itchy spots

Not known: frequency cannot be estimated from the available data
A form of diabetes primarily due to kidney disease
Kidney disorders leading to death of tubular epithelial cells forming the kidney tubules

You may experience one or more of these symptoms and/or conditions. You must inform your doctor as soon as possible if you begin to experience any of these side effects.
If you have any doubts about any side effect, discuss them with your doctor.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pemetrexed Pfizer

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging and on the label of the vial, following the abbreviation "Exp". The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Infusion solution: chemical and physical stability of the pemetrexed infusion solution during use has been demonstrated for 24 hours at a temperature between 2 °C and 8 °C. From a microbiological standpoint, the medicine should be used immediately. Otherwise, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2 °C and 8 °C.
Before administration, parenteral medicinal products should be visually inspected for the presence of particles and discoloration. Do not administer if particles are observed.
This medicine is for single use only; any unused solution must be disposed of in accordance with local legal requirements.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Pemetrexed Pfizer contains
The active substance is pemetrexed. Each ml of concentrate contains pemetrexed disodium equivalent to
25 mg of pemetrexed. Prior to administration, further dilution by healthcare personnel is required.
Each 4 ml vial of concentrate contains pemetrexed disodium equivalent to 100 mg of
pemetrexed.
Each 20 ml vial of concentrate contains pemetrexed disodium equivalent to 500 mg of
pemetrexed.
Each 40 ml vial of concentrate contains pemetrexed disodium equivalent to 1,000 mg of
pemetrexed.
The other components are monothioglycerol, sodium hydroxide (to adjust pH), and water for
injections. See section 2 “Pemetrexed Pfizer contains sodium”.

Description of the appearance of Pemetrexed Pfizer and contents of the pack
Pemetrexed Pfizer concentrate for solution for infusion (sterile concentrate) is a clear, colourless to pale yellow or yellowish-green solution, practically free from visible particles, in a glass vial.
Each pack contains one vial of 100 mg/4 ml, 500 mg/20 ml or 1,000 mg/40 ml of
pemetrexed (as pemetrexed disodium).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Pfizer Service Company BV
Hoge Wei 10
1930 Zaventem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

BE LT
Pfizer SA/NV Pfizer Luxembourg SARL filialas Lietuvoje
Tél/Tel: +32 2 554 62 11 Tel. + 370 52 51 4000

BG LU
Пфайзер Люксембург САРЛ, Клон България Pfizer SA/NV
Тел.: +359 2 970 4333 Tél/Tel: +32 2 554 62 11

CZ HU
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420-283-004-111 Tel: + 36 1 488 37 00

DK MT
Pfizer ApS Drugsales Ltd
Tlf: + 45 44 20 11 00 Tel.: + 356 21 419 070/1/2

DE NL
PFIZER PHARMA GmbH Pfizer bv
Tel: + 49 (0) 30 550055-51000 Tel: +31 (0) 800 63 34 636

EE NO
Pfizer Luxembourg SARL Eesti filiaal Pfizer AS
Tel: +372 666 7500 Tlf: +47 67 52 61 00

EL AT
Pfizer ΕΛΛΑΣ A.E. Pfizer Corporation Austria Ges.m.b.H.
Τηλ.: +30 210 6785 800 Tel: +43 (0)1 521 15-0

ES PL
Pfizer, S.L. Pfizer Polska Sp. z o.o.
Tel: +34 91 490 99 00 Tel: +48 22 335 61 00

FR PT
Pfizer Laboratórios Pfizer, Lda.
Tél: + 33 (0)1 58 07 34 40 Tel: + 351 21 423 55 00

HR RO
Pfizer Croatia d.o.o. Pfizer România S.R.L.
Tel: +385 1 3908 777 Tel: +40 (0)21 207 28 00

IE SI
Pfizer Healthcare Ireland Pfizer Luxembourg SARL
Tel: 1800 633 363 (toll free) Pfizer, podružnica za svetovanje s področja
+44 (0) 1304 616161 farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IS SK
Icepharma hf. Pfizer Luxembourg SARL, organizačná zložka
Sími: +354 540 8000 Tel: +421–2–3355 5500

IT FI
Pfizer S.r.l. Pfizer Oy
Tel: +39 06 33 18 21 Puh/Tel: +358 (0)9 430 040

CY SE
Pfizer Ελλάς Α.Ε. (Cyprus Branch) Pfizer AB
Τηλ.: +357 22817690 Tel: +46 (0)8 550 520 00

LV UK (Northern Ireland)
Pfizer Luxembourg SARL filiāle Latvijā Pfizer Limited
Tel.: + 371 670 35 775 Tel: + 44 (0) 1304 616161

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu
This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling, and disposal

1. During dilution of pemetrexed for intravenous infusion administration, use aseptic techniques.
2. Calculate the required dose and number of Pemetrexed Pfizer vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the labeled amount.
3. The appropriate volume of pemetrexed solution must be further diluted to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection, without preservatives, and administered as an intravenous infusion over 10 minutes.
4. The pemetrexed infusion solution prepared as described above is compatible with infusion bags and administration sets lined with polyvinyl chloride and polyolefins. Pemetrexed is incompatible with solvents containing calcium, including sodium lactate (Ringer's lactate) solution for injection and Ringer's solution for injection.
5. Prior to administration, parenteral medicinal products should be inspected visually for particulate matter and discoloration. Do not administer if particulate matter is observed.
6. Pemetrexed solutions are for single use only. Unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local legal requirements.

Precautions for preparation and administration: As with other potentially toxic antineoplastic agents, caution should be exercised when handling and preparing pemetrexed infusion solutions. Use of gloves is recommended. If a pemetrexed solution comes into contact with the skin, immediately and thoroughly wash 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, which were not considered severe by the investigator. Extravasation should be managed according to standard procedures for non-vesicant agents.