PEMETREXED 100 mg Powder For Concentrate For Infusion Solution

Зміст інструкції

1. Pemetrexed Fresenius Kabi 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion
   1. What is Pemetrexed Fresenius Kabi and what is it used for
   2. What you need to know before using Pemetrexed Fresenius Kabi
   3. How to use Pemetrexed Fresenius Kabi
   4. Possible side effects
   5. How to store Pemetrexed Fresenius Kabi
   6. Contents of the pack and other information
2. Pemetrexed Fresenius Kabi 25 mg/ml concentrate for solution for infusion
   1. What is Pemetrexed Fresenius Kabi and what is it used for
   2. What you need to know before using Pemetrexed Fresenius Kabi
   3. How to use Pemetrexed Fresenius Kabi
   4. Possible side effects
   5. How to store Pemetrexed Fresenius Kabi
   6. Package contents and other information

Pemetrexed Fresenius Kabi 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion

pemetrexed

Read this leaflet carefully before you receive this medicine as it contains
important information for you.

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

Contents of this leaflet

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

1. What is Pemetrexed Fresenius Kabi and what is it used for

Pemetrexed Fresenius Kabi is a medicine used in the treatment of tumors.
Pemetrexed Fresenius Kabi is administered in association with cisplatin, another anti-cancer drug
as treatment for malignant pleural mesothelioma, a form of cancer that
affects the tissue lining the lungs, to patients who have not received previous
chemotherapy.
In addition, Pemetrexed Fresenius Kabi, in association with cisplatin, is administered for
first-line therapy in patients with advanced stage lung cancer.
Pemetrexed Fresenius Kabi may be prescribed for advanced stage lung cancer if the
disease has responded to treatment or if it remains largely unchanged after initial chemotherapy.
In addition, Pemetrexed Fresenius Kabi is a treatment for patients with advanced stage lung
cancer whose disease has progressed after a previous initial chemotherapeutic treatment.

2. What you need to know before using Pemetrexed Fresenius Kabi

Do not use Pemetrexed Fresenius Kabi

• if you are allergic 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 Fresenius Kabi.
• if you have recently had or are about to have the vaccination for yellow fever.

Warnings and precautions
Talk to your doctor or hospital pharmacist before taking Pemetrexed Fresenius Kabi.
If you have or have had kidney problems, tell your doctor or hospital pharmacist as you may
not be able to receive Pemetrexed Fresenius Kabi.
Before each infusion, blood tests will be performed to assess whether you have sufficient
liver and kidney function and to check that you have enough blood cells to receive
Pemetrexed Fresenius Kabi. The doctor may decide to change the dose or delay treatment
depending on your general condition and if the blood test (blood cells) results are
inadequate (too low). Also, if you are receiving cisplatin, the 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 had or will be undergoing radiation treatment, tell your doctor, as
Pemetrexed Fresenius Kabi may cause an early or delayed reaction due to
radiation treatment.
If you have been vaccinated recently, tell your doctor, as Pemetrexed Fresenius Kabi
may cause adverse effects.
If you have heart disease or a history of heart disease, tell your doctor.
If you have fluid buildup around your lungs, the doctor may decide to remove the
fluid before administering Pemetrexed Fresenius Kabi.

Children and adolescents
This medicine should not be used in children and adolescents because there is no experience
in children and adolescents under 18 years of age

Other medicines and Pemetrexed Fresenius Kabi
Tell your doctor if you are taking, have recently taken or might take any
medicine for pain or inflammation (swelling), such as medicines called
“non-steroidal anti-inflammatory drugs” (NSAIDs), including over-the-counter medicines
(such as ibuprofen). There are many types of NSAIDs with different durations of action. Based on
the planned date for the infusion of Pemetrexed Fresenius Kabi and/or your kidney function, the 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 if any of your medicines is an NSAID.
Tell your doctor if you are taking medicines called proton pump inhibitors (omeprazole,
esomeprazole, lansoprazole, pantoprazole and rabeprazole), used to treat heartburn and
acid reflux.
Tell your doctor or hospital pharmacist if you are taking or have recently taken any
other medicines, even those available without a prescription.

Pregnancy
If you are pregnant, suspect you are pregnant or are planning a pregnancy, tell your doctor. The use
of Pemetrexed Fresenius Kabi during pregnancy should be avoided. The doctor will talk to you about
the potential risks of taking Pemetrexed Fresenius Kabi during pregnancy. Women must
use an effective method of contraception during treatment with Pemetrexed Fresenius Kabi
and for 6 months after receiving the last dose.

Breastfeeding
If you are breastfeeding, tell your doctor.
Breastfeeding must be stopped during treatment with Pemetrexed Fresenius Kabi.

Fertility
Men are advised not to father a child during treatment with Pemetrexed Fresenius
Kabi until 3 months afterwards and therefore to use effective contraception during treatment with
Pemetrexed Fresenius Kabi or until 3 months afterwards. If you wish to father a child during
treatment or within 3 months afterwards, ask your doctor or pharmacist for advice. Pemetrexed Fresenius
Kabi may affect your ability to have children. Talk to your doctor for advice on
ways to preserve sperm before starting therapy.

Driving and operating machinery
Pemetrexed Fresenius Kabi may cause fatigue. Be careful when driving a vehicle or
operating machinery.

3. How to use Pemetrexed Fresenius Kabi

The dose of Pemetrexed Fresenius Kabi is 500 mg per each square meter of body surface area. Your
height and weight will be measured to calculate your body surface area. The doctor will use this
body surface area to calculate the right dose for you. This dosage may be adjusted or treatment may
be delayed depending on blood tests and your overall condition. A
hospital pharmacist, nurse or doctor will have mixed Pemetrexed Fresenius Kabi with
5% glucose solution for intravenous infusion before administering it to you.
You will always receive Pemetrexed Fresenius Kabi as an infusion into a vein. The infusion will last about 10
minutes.
When Pemetrexed Fresenius Kabi is used in combination with cisplatin:
the doctor or hospital pharmacist will calculate the dose you need based on your height and
your weight. Cisplatin is also administered as an infusion into a vein, approximately 30 minutes after
the Pemetrexed Fresenius Kabi infusion is completed. The cisplatin infusion will last approximately 2
hours.
Generally, the infusion will be given to you once every 3 weeks.
Additional medicines:
Corticosteroids: the 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 Fresenius Kabi. This medicine is given to reduce the
frequency and severity of skin reactions that may occur during cancer treatment.
Vitamin supplement: the doctor will prescribe folic acid (vitamin) or a multivitamin product
containing folic acid (350-1000 micrograms) orally that you must take once a day
while being treated with Pemetrexed Fresenius Kabi. You must take at least 5 doses during the
seven days before the first dose of Pemetrexed Fresenius Kabi. You must continue to take
folic acid for 21 days after the last dose of Pemetrexed Fresenius Kabi. You will also receive
an injection of vitamin B12 (1000 micrograms) in the week before the administration of
Pemetrexed Fresenius Kabi and then approximately every 9 weeks (corresponding to 3 treatment cycles with
Pemetrexed Fresenius Kabi). Vitamin B12 and folic acid are given to reduce the
possible toxic effects of cancer treatment.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
You should immediately contact your doctor if you notice any of the following side effects:

• Fever or infection (common or very common respectively): 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). Infection (sepsis) can be serious and could lead to death.
• If you begin to feel chest pain (common) or experience an increased heartbeat (uncommon).
• If you have pain, redness, swelling or sores in your mouth (very common).
• Allergic reaction: if you develop a skin rash (very common) /burning or tingling sensation (common) or fever (common). Rarely, skin reactions can be severe and could lead to death. Contact your doctor if a severe rash, or itching, or blisters develop (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired, feel faint, feel short of breath easily or are pale (as you may have less hemoglobin than normal, which is very common).
• If you experience bleeding from the gums, nose or mouth or any bleeding that does not tend to stop, reddish or slightly pink urine, unexplained bruising (as you may have fewer platelets than normal, which is common).
• If you experience sudden shortness of breath, severe chest pain or have blood in your sputum when coughing (uncommon) (may indicate a blood clot in the pulmonary blood vessels).

Other side effects with pemetrexed may include:

Very common (may affect more than 1 in 10 people)
Infection
Pharyngitis (sore throat)
Low number of neutrophils (a type of white blood cells)
Low number of white blood cells in the blood
Low level of hemoglobin
Pain, redness, swelling or ulcers in the mouth
Loss of appetite
Vomiting
Diarrhea
Nausea
Redness of the skin
Skin peeling
Abnormal blood tests showing reduced kidney function
Fatigue (tiredness)

Common (may affect up to 1 in 10 people)
Bloodstream infection
Fever with low number of neutrophils (a type of white blood cells)
Low platelet count
Allergic reactions
Loss of body fluids
Taste alteration
Damage to motor nerves that may cause muscle stiffness and atrophy which can cause muscle weakness
and primary atrophy (wasting) in the arms and legs
Damage to sensory nerves that can cause loss of sensation, burning and unstable gait
Dizziness
Inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the white
part of the eye)
Dry eye
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).
Swelling of the eyelids
Eye disorders with dryness, tearing, irritation and/or pain
Heart failure (a condition that affects the heart muscle's ability to pump)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increased levels of chemicals produced by the liver in the blood
Increased skin pigmentation
Skin itching
Widespread red spots
Hair loss
Hives
Kidneys stopping 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
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
Insufficient blood supply to the limbs
Blockage in the lungs, of one of the pulmonary arteries
Inflammation and scarring of the lining of the lungs with breathing problems
Bright red blood from the anus
Bleeding from the gastrointestinal tract
Rupture of the intestine
Inflammation of the lining of the esophagus
Inflammation of the lining 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 mucosa of the esophagus caused by
radiation therapy
Inflammation of the lung 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 that develops 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 lead to life-threatening
conditions)
Autoimmune disorders resulting in sudden skin redness and blisters on the legs, arms and
abdomen
Inflammation of the skin characterized by the presence of blisters that fill with fluid
Skin fragility, blisters and erosion and scarring of the skin
Redness, pain and swelling mainly of the lower limbs
Inflammation of the skin and fat under the skin (pseudocellulitis)
Inflammation of the skin (dermatitis)
Skin that becomes inflamed, itchy, red, cracked and rough
Intensely itchy spots

Not known: (frequency cannot be estimated based on available data)
Form of diabetes primarily due to kidney disease
Kidney disorders involving the death of tubular epithelial cells that form the renal tubules
You may experience one of these symptoms and/or conditions. You should tell your doctor as soon as
possible when you start to have one of these side effects.
If you have any doubts about any side effect, talk to your doctor.
Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also
report side effects directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse .
By reporting side effects you can help provide more information on the safety
of this medicine.

5. How to store Pemetrexed Fresenius Kabi

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 label and on the package after
EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Reconstituted and infusion solutions: the product must be used immediately. If prepared
as indicated, the chemical and physical stability during use of reconstituted pemetrexed solutions has been
demonstrated for 24 hours at refrigerated temperature. For pemetrexed infusion solutions, the
chemical and physical stability during use has been demonstrated for 21 days at refrigerated temperature and for
7 days at 25°C.
This medicine must not be used if there is any trace of particles.
This medicine is for single use only.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Pemetrexed Fresenius Kabi contains
The active ingredient is pemetrexed.
Pemetrexed Fresenius Kabi 100 mg: each vial contains 100 milligrams of pemetrexed (as
pemetrexed diacid).
Pemetrexed Fresenius Kabi 500 mg: each vial contains 500 milligrams of pemetrexed (as
pemetrexed diacid)..
After reconstitution, the solution contains 25 mg/ml of pemetrexed. Further dilution is
required by healthcare professionals before administration.
The other components are mannitol, hydrochloric acid and trometamol.

Description of Pemetrexed Fresenius Kabi and contents of the pack
Pemetrexed Fresenius Kabi is a powder for concentrate for solution for infusion in a
glass vial. It is a lyophilized powder or solid of varying color from white to off-white.
It is available in packs of 1 vial.

Marketing Authorisation Holder
Fresenius Kabi Deutschland GmbH
Else-Kröner-Straße 1,
61352 Bad Homburg v.d. Höhe
Germany
Manufacturer
Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany
Fresenius Kabi Polska Sp. z o.o.
ul. Sienkiewicza 25, Kutno, 99-300, Poland
Fresenius Kabi France- Louviers
6 rue du Rempart
Louviers, 27400
France
For further information on this medicinal product, contact the marketing authorisation holder.

Other sources of information
More detailed information on this medicinal product is available on the website of the
European Medicines Agency http://www.ema/europa.eu
---------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Instructions for use, handling and disposal.

• During the reconstitution and further dilution of pemetrexed for the administration of the intravenous infusion, use aseptic techniques.
• Calculate the dose and the number of vials of Pemetrexed Fresenius Kabi needed. Each vial contains an excess of pemetrexed to facilitate dispensing the amount indicated on the label.
• Pemetrexed Fresenius Kabi 100 mg:
• Reconstitute each 100 mg vial with 4.2 ml of 5% glucose solution for intravenous infusion to obtain a solution containing 25 mg/ml of pemetrexed.
• Pemetrexed Fresenius Kabi 500 mg:
• Reconstitute each 500 mg vial with 20 ml of 5% glucose solution for intravenous infusion 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 ranges from colorless to yellow or yellowish-green without negatively affecting product quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.
• The appropriate volume of reconstituted pemetrexed solution must be further diluted to a volume of 100 ml with 5% glucose solution for intravenous infusion and administered by intravenous infusion over 10 minutes.
• The pemetrexed infusion solutions prepared as described above are compatible with
• polyvinyl chloride and polyolefin-coated infusion bags and administration sets. Pemetrexed is incompatible with solvents containing calcium, including Ringer's lactate for injectable preparations and Ringer's solution for injectable preparations.
• Pemetrexed Fresenius Kabi contains trometamol as an excipient. Trometamol is incompatible with cisplatin, resulting in cisplatin degradation. This medicinal product must not be mixed with other medicinal products. Intravenous administration lines must be flushed after administration of Pemetrexed Fresenius Kabi.
• Before administration, parenteral medicines must be visually inspected for the presence of particles and color changes. Do not administer if particles are observed.
• Pemetrexed solutions are for single use only. Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.

Precautions for preparation and administration:As with other potentially toxic antitumor 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 water and soap. If pemetrexed solutions come into contact with mucous membranes,
wash thoroughly with water. Pregnant women should avoid contact with cytotoxic medicines. Pemetrexed
is not vesicant. There is no specific antidote for pemetrexed extravasation. Some cases of pemetrexed
extravasation have been reported that were not considered serious by the investigator. Extravasation should
be managed according to standard procedures as for other non-vesicant agents.

Pemetrexed Fresenius Kabi 25 mg/ml concentrate for solution for infusion

pemetrexed

Read this leaflet carefully before you receive this medicine as it contains
important information for you.

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

Contents of this leaflet

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

1. What is Pemetrexed Fresenius Kabi and what is it used for

Pemetrexed Fresenius Kabi is a medicine used in the treatment of tumors.
Pemetrexed Fresenius Kabi is administered in association with cisplatin, another anti-cancer drug
as treatment for malignant pleural mesothelioma, a form of cancer that
affects the tissue lining the lungs, to patients who have not received previous
chemotherapy.
In addition, Pemetrexed Fresenius Kabi, in association with cisplatin, is administered for
first-line therapy in patients with advanced stage lung cancer.
Pemetrexed Fresenius Kabi may be prescribed for advanced stage lung cancer if the
disease has responded to treatment or if it remains largely unchanged after initial chemotherapy.
In addition, Pemetrexed Fresenius Kabi is a treatment for patients with advanced stage lung
cancer whose disease has progressed after previous initial chemotherapeutic treatment.

2. What you need to know before using Pemetrexed Fresenius Kabi

Do not use Pemetrexed Fresenius Kabi

• if you are allergic to pemetrexed or to any of the other ingredients of Pemetrexed Fresenius Kabi (listed in section 6).
• if you are breastfeeding; you must stop breastfeeding during treatment with Pemetrexed Fresenius Kabi.
• if you have recently had or are about to have the yellow fever vaccination.

Warnings and precautions
Talk to your doctor or hospital pharmacist before taking Pemetrexed Fresenius Kabi.
If you have or have had kidney problems, tell your doctor or hospital pharmacist as you may
not be able to receive Pemetrexed Fresenius Kabi.
Before each infusion, blood tests will be performed to assess whether you have sufficient
liver and kidney function and to check that you have enough cells in your blood to receive
Pemetrexed Fresenius Kabi. The doctor may decide to change the dose or delay treatment
depending on your general condition and if the blood test (blood cells) results are not
adequate (too low). Also, if you are receiving cisplatin, the 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 had or will be undergoing radiation treatment, tell your doctor, as
with Pemetrexed Fresenius Kabi, an early or delayed reaction due to radiation treatment may occur.
If you have been vaccinated recently, tell your doctor, as with Pemetrexed Fresenius Kabi
this may cause adverse effects.
If you have heart disease or a history of heart disease, tell your doctor.
If you have fluid buildup around your lungs, your doctor may decide to remove the
fluid before giving you Pemetrexed Fresenius Kabi.

Children and adolescents
This medicine should not be used in children and adolescents because there is no experience in
children and adolescents under 18 years of age

Other medicines and Pemetrexed Fresenius Kabi
Tell your doctor if you are taking any medicine for pain or inflammation (swelling), such as medicines called “non-steroidal anti-inflammatory drugs”
(NSAIDs), including over-the-counter medicines (such as ibuprofen). There are
many types of NSAIDs with different durations of activity. Depending on the scheduled date for the
infusion of Pemetrexed Fresenius Kabi and/or your kidney function, the 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 if
any of your medicines is an NSAID.
Tell your doctor if you are taking medicines called proton pump inhibitors (omeprazole,
esomeprazole, lansoprazole, pantoprazole and rabeprazole), used to treat heartburn and
acid reflux.
Tell your doctor or hospital pharmacist if you are taking or have recently taken any
other medicines, even those available without a prescription.

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

Breastfeeding
If you are breastfeeding, tell your doctor.
Breastfeeding must be stopped during treatment with Pemetrexed Fresenius Kabi.

Fertility
Men are advised not to father a child during treatment with Pemetrexed Fresenius
Kabi until 3 months after treatment and to use effective contraception during treatment with
Pemetrexed Fresenius Kabi or until 3 months after treatment. If you want to father a child during
treatment or within 3 months after treatment, ask your doctor or pharmacist for advice. Pemetrexed Fresenius
Kabi may affect the ability to have children. Talk to your doctor for advice on
ways to preserve sperm before starting therapy.

Driving and operating machinery
Pemetrexed Fresenius Kabi can cause fatigue. Be careful when driving a vehicle or
operating machinery.
Pemetrexed Fresenius Kabi contains 964 mg of hydroxypropyl betadex per 100 mg of pemetrexed.
If you have kidney disease, talk to your doctor before receiving this medicine.

3. How to use Pemetrexed Fresenius Kabi

The dose of Pemetrexed Fresenius Kabi is 500 mg per each square meter of body surface area. Your
height and weight will be measured to calculate your body surface area. The doctor will use this
body surface area to calculate the right dose for you. This dosage may be adjusted or treatment may be
delayed depending on blood tests and your overall condition. A
hospital pharmacist, nurse or doctor will have mixed the powder of Pemetrexed Fresenius
Kabi with sodium chloride 9 mg/ml (0.9%) injectable solution or with glucose 5% solution for
intravenous infusion before administering it to you.
You will always receive Pemetrexed Fresenius Kabi via infusion into a vein. The infusion will last about 10
minutes.
When Pemetrexed Fresenius Kabi is used in combination with cisplatin:
The doctor or hospital pharmacist will calculate the dose you need based on your height and
weight. Cisplatin is also administered via infusion into a vein, approximately 30 minutes after
the Pemetrexed Fresenius Kabi infusion is completed. The cisplatin infusion will last about 2
hours.
Generally, the infusion will be given to you once every 3 weeks.
Additional medicines:
Corticosteroids: the doctor will prescribe steroid tablets (equivalent to 4 milligrams of
dexamethasone twice a day) that you must take the day before, the day of and the day after
treatment with Pemetrexed Fresenius Kabi. This medicine is given to you to reduce the
frequency and severity of skin reactions that may occur during cancer treatment.
Vitamin supplement: the doctor will prescribe folic acid (vitamin) or a multivitamin product
containing folic acid (350-1000 micrograms) orally that you must take once a day
while you are being treated with Pemetrexed Fresenius Kabi. You must take at least 5 doses during the seven
days before the first dose of Pemetrexed Fresenius Kabi. You must continue to take folic acid for 21
days after the last dose of Pemetrexed Fresenius Kabi. You will also receive an injection of
vitamin B12 (1000 micrograms) in the week before the administration of Pemetrexed
Fresenius Kabi and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed
Fresenius Kabi). Vitamin B12 and folic acid are given to you to reduce the possible toxic effects of
cancer treatment.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

• Fever or infection (common or very common respectively): 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). Infection (sepsis) can be serious and could lead to death.
• If you start to feel chest pain (common) or have an increased heartbeat (uncommon).
• If you have pain, redness, swelling or sores in your 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 could lead to death. Contact your doctor if a severe rash, or itching, or blisters appear (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired, feel faint, feel short of breath easily or are pale (as you may have less hemoglobin than normal 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, unexplained bruising (as you may have fewer platelets than normal which is common).
• If you experience sudden shortness of breath, severe chest pain or have cough with blood in your sputum (uncommon) (may indicate a blood clot in the pulmonary blood vessels).

Other side effects with Pemetrexed may include:

Very common (may affect more than 1 in 10 people)
Infection
Pharyngitis (sore throat)
Low number of neutrophils (a type of white blood cells)
Low number of white blood cells
Low level of hemoglobin
Pain, redness, swelling or ulcers in the mouth
Loss of appetite
Vomiting
Diarrhea
Nausea
Redness of the skin
Skin peeling
Abnormal blood tests showing reduced kidney function
Fatigue (tiredness)

Common (may affect up to 1 in 10 people)
Bloodstream infection
Fever with low number of neutrophils (a type of white blood cells)
Low platelet count
Allergic reactions
Loss of body fluids
Alteration of taste
Damage to motor nerves that may cause muscle stiffness and atrophy which can cause muscle weakness
and primary atrophy (wasting) in the arms and legs
Damage to sensory nerves that can cause loss of sensation, burning and unstable gait
Dizziness
Inflammation or swelling of the conjunctiva (the membrane that lines the eyelids and covers the white
part of the eye)
Dry eye
Excessive tearing
Dryness of the conjunctiva (the membrane that lines the eyelids and covers the white part of the eye) and
the cornea (the clear layer in front of the iris and pupil).
Swelling of the eyelids
Eye disorders with dryness, tearing, irritation and/or pain
Heart failure (a condition that affects the heart's ability to pump)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increased levels of chemicals produced by the liver in the blood
Increased skin pigmentation
Skin itching
Widespread red spots
Hair loss
Hives
Kidneys stopping 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
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
Poor blood distribution to the limbs
Blockage in the lungs, of one of the pulmonary arteries
Inflammation and scarring of the lining of the lungs with breathing problems
Bright red blood from the anus
Bleeding from the gastrointestinal tract
Rupture of the intestine
Inflammation of the lining of the esophagus
Inflammation of the lining 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 surface of the mucosa of the esophagus caused by
radiotherapy
Inflammation of the lung caused by radiotherapy

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
Redness of the skin
Sudden redness of the skin that develops 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 lead to life
threatening)
Autoimmune disorders resulting in sudden redness of the skin and blisters on the legs, arms and
abdomen
Inflammation of the skin characterized by the presence of blisters that fill with fluid
Fragility of the skin, blisters and erosion and scarring of the skin
Redness, pain and swelling mainly of the lower limbs
Inflammation of the skin and fat under the skin (pseudocellulitis)
Inflammation of the skin (dermatitis)
Skin that becomes inflamed, itchy, red, cracked and rough
Intensely itchy spots

Frequency not known: (frequency cannot be estimated from available data)
A form of diabetes primarily due to kidney disease
Kidney disorders involving the death of tubular epithelial cells that form the renal tubules
You may experience one of these symptoms and/or conditions. You should tell your doctor as
soon as possible when you start to have one of these side effects.
If you get any side effects, talk to your doctor or pharmacist.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through
the national reporting system at https://www.aifa.gov.it/content/segnalazioni-
reazioni-avverse. By reporting side effects you can help provide more information
on the safety of this medicine.

5. How to store Pemetrexed Fresenius Kabi

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 box and label after
EXP. The expiry date refers to the last day of that month.
Store at a temperature below 25 °C
Keep the vial in its outer packaging to protect it from light.
Infusion solutions: the product must be used immediately. If prepared as indicated, the
chemical and physical stability during use of diluted pemetrexed solutions has been demonstrated for 21
days at refrigerated temperature and 7 days at 25°C.
This medicine should not be used if there is any evidence of particles.
This medicine is for single use only.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Pemetrexed Fresenius Kabi contains
The active ingredient is pemetrexed.
One ml of concentrate contains 25 mg of pemetrexed.
After dilution, one 4 ml vial of concentrate contains 100 mg of pemetrexed (as
pemetrexed disacid)
One 20 ml vial of concentrate contains 500 mg of pemetrexed (as pemetrexed disacid)
One 40 ml vial of concentrate contains 1,000 mg of pemetrexed (as pemetrexed disacid)
The other ingredients are hydroxypropyl betadex, hydrochloric acid, trometamol and water for
injections.

Description of the appearance of Pemetrexed Fresenius Kabi and contents of the pack
Pemetrexed Fresenius Kabi is a concentrate for solution for infusion (sterile concentrate) in a
glass vial. It is a solution from colourless to slightly yellowish or yellowish-green.
It is available in packs of 1 vial.

Marketing authorisation holder
Fresenius Kabi Deutschland GmbH
Else Kröner Straße 1,
61352 Bad Homburg v.d. Höhe
Germany

Manufacturer
Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany
Fresenius Kabi Polska Sp. z o.o.
ul. Sienkiewicza 25, Kutno, 99-300, Poland
For further information on this medicinal product, contact the marketing authorisation holder.

Other sources of information
More detailed information on this medicinal product is available on the website of the
European Medicines Agency http://www.ema/europa.eu
<---------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Instructions for use, handling and disposal.

• During the dilution of pemetrexed for the administration of intravenous infusion, use aseptic techniques.
• Calculate the dose and the number of vials of Pemetrexed Fresenius Kabi required.
• The appropriate volume of Pemetrexed Fresenius Kabi must be diluted to a volume of 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection or with glucose 5% for intravenous infusion and administered by intravenous infusion in 10 minutes.
• Infusion solutions of pemetrexed prepared as described above are compatible with polyvinyl chloride and polyolefin coated infusion sets and administration sets. Pemetrexed is incompatible with solvents containing calcium, including Ringer’s lactate for injection and Ringer’s solution for injection.
• Pemetrexed Fresenius Kabi contains trometamol as an excipient. Trometamol is incompatible with cisplatin, resulting in cisplatin degradation. This medicinal product must not be mixed with other medicinal products. Intravenous administration lines must be flushed after the administration of Pemetrexed Fresenius Kabi.
• Before administration, parenteral medicinal products must be visually inspected for the presence of particles and changes in colour. Do not administer if the presence of particles is observed.
• Pemetrexed solutions are for single use only. Unused medicinal product and waste material derived from such medicinal product must be disposed of in accordance with local regulations.

Precautions for preparation and administration:As with other potentially toxic antitumor 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 water and soap. If pemetrexed solutions come into contact with mucous membranes, wash thoroughly with water. Pregnant women
should avoid contact with cytotoxic medicinal products. Pemetrexed is not vesicant. There is no
specific antidote for pemetrexed extravasation. Some cases of pemetrexed extravasation have been reported that were not considered serious by the investigator. Extravasation should be managed
according to standard procedures as for other non-vesicant agents.

APPENDIX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE
MARKETING AUTHORISATION TERMS
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee (PRAC) of the
Periodic Safety Update Report (PSUR) for pemetrexed, the scientific conclusions of the PRAC are as follows:
In light of the available data on the pharmacokinetics of pemetrexed, considering that in vitro studies have indicated that pemetrexed is actively secreted by the organic anion transporter OAT3 (organic anion transporter 3) and considering the IC50 values
for proton pump inhibitors, the PRAC considers that a drug-drug interaction
between proton pump inhibitors and pemetrexed is at least a reasonable possibility. The
PRAC concluded that the product information for medicinal products containing pemetrexed
must be amended accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the related
overall conclusions and with the justification for the recommendation.

Justification for the variation of the marketing authorisation terms
Based on the scientific conclusions on pemetrexed, the CHMP considers that the benefit/risk ratio of medicinal products containing pemetrexed remains unchanged, subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation.