PEMETREXED 25 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. Pemetrexed Zentiva 25 mg/ml concentrate for solution for infusion
   1. What is Pemetrexed Zentiva and what is it used for
   2. What you need to know before you take Pemetrexed Zentiva
   3. How to take Pemetrexed Zentiva
   4. Possible side effects
   5. How to store Pemetrexed Zentiva
   6. Contents of the pack and other information

Pemetrexed Zentiva 25 mg/ml concentrate for solution for infusion

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, pharmacist or nurse.
• If any side effect occurs, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

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

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

2. What you need to know before you take Pemetrexed Zentiva

Do not take Pemetrexed Zentiva:

• if you are allergic to pemetrexed or any of the other ingredientsof this medicine (listed in section 6).
• if you are breast-feeding; you must stop breast-feeding during treatment with Pemetrexed Zentiva.
• if you have recently had or are about to have the vaccination for yellow fever.

Warnings and precautions:
Talk to your doctor, pharmacist or nurse before you receive Pemetrexed Zentiva.
If you have or have had kidney problems, tell your doctor or hospital pharmacist because you may not
be able to receive Pemetrexed Zentiva.
Before each infusion, you will have blood tests to assess whether you have sufficient
liver and kidney function and to check that you have enough cells in your blood to receive
Pemetrexed Zentiva. The doctor may decide to change the dose or delay treatment depending on
your overall condition and if your blood cell count is 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 having radiation treatment, tell your doctor, as
Pemetrexed Zentiva may cause an early or delayed reaction due to radiation treatment.
If you have been vaccinated recently, tell your doctor, as Pemetrexed Zentiva
may cause harmful effects.
If you have heart disease or a history of heart disease, tell your doctor.
If you have fluid build-up around your lungs, your doctor may decide to remove the
fluid before giving you Pemetrexed Zentiva.

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

Other medicines and Pemetrexed Zentiva
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including those available without a prescription.
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 medicines purchased without a prescription (such as ibuprofen). There are many
types of NSAIDs with different durations of action. Depending on the date scheduled for the infusion of Pemetrexed
Zentiva 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 if any of your medicines
is an NSAID.

Pregnancy, breast-feeding and fertility

Pregnancy
If you are pregnant, if you suspect you are pregnant or are planning to have a baby, ask your
doctor or pharmacist for advice before taking this medicine. Use of Pemetrexed Zentiva during
pregnancy should be avoided. The doctor will discuss with you the potential risk of taking Pemetrexed
Zentiva during pregnancy. Women must use effective contraception during
treatment with Pemetrexed Zentiva.

Breast-feeding
If you are breast-feeding, tell your doctor.
Breast-feeding must be stopped during treatment with Pemetrexed Zentiva.

Fertility
Men are advised not to father a child during treatment with Pemetrexed Zentiva until
6 months after treatment and therefore to use effective contraception during treatment with Pemetrexed
Zentiva or until 6 months after treatment. If you wish to father a child during treatment or within 6 months
afterwards, ask your doctor or pharmacist for advice. You should ask about
methods of sperm preservation before starting therapy.

Driving and using machines
Pemetrexed Zentiva can cause fatigue. Be careful when driving a vehicle or using
machines.

3. How to take Pemetrexed Zentiva

The dose of Pemetrexed Zentiva 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 your blood cell count and your general condition.
A hospital pharmacist, a nurse or a doctor will have mixed the Pemetrexed
Zentiva solution with an injectable solution of 0.9% sodium chloride or 5% dextrose before it is
administered to you.
You will receive Pemetrexed Zentiva always by infusion into a vein. The infusion will last approximately 10 minutes.

When Pemetrexed Zentiva 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 by infusion into a vein, approximately 30 minutes after
the Pemetrexed Zentiva infusion has been completed. The cisplatin infusion will last approximately 2 hours.
Usually you should receive the infusion 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 Zentiva. 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 you are being treated
with Pemetrexed Zentiva. You must take at least 5 doses during the 7 days before the first dose of
Pemetrexed Zentiva. You must continue to take folic acid for 21 days after the last dose of
Pemetrexed Zentiva. You will also receive an injection of vitamin B (1000 micrograms) in the week
before the administration of Pemetrexed Zentiva and then approximately every 9 weeks (corresponding to 3
treatment cycles with Pemetrexed Zentiva). Vitamin B and folic acid are administered 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 begin to experience chest pain(common) or have an increased heart rate(uncommon).
• If you have pain, redness, swelling or sores in your mouth(very common).
• Allergic reaction: if you develop 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 skin rash, or itching, or blistersappear (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired, feel faint, feel short of breatheasily or are pale(as you may have less haemoglobin than normal, which is very common).
• If you experience bleeding from the gums, nose or mouthor 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 painor have coughing up blood in your sputum(uncommon) (this may indicate a blood clot in the lung vessels).

Side effects with Pemetrexed Zentiva can 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 in the
blood) ·Few white blood cells in the blood ·Loss of appetite ·Vomiting ·Diarrhoea ·Nausea

• Skin peeling ·Abnormal blood tests showing reduced kidney function
• Fatigue (tiredness).

Common(may affect up to 1 in 10 people):
Bloodstream infection ·Low number of platelets ·Loss of body fluids ·Altered taste ·Damage
to motor nerves which may cause muscle weakness and atrophy (wasting) primarily in the arms
and legs ·Damage to sensory nerves which may 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
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
ability of the heart muscle to pump) ·Irregular heartbeat ·Indigestion ·Constipation

• Abdominal pain ·Liver: increase in blood of chemicals produced by the liver · Increased skin pigmentation ·Itching of the skin ·Skin rash on the body where each mark resembles a target ·Hair loss ·Hives ·Kidneys stopping working ·Reduced kidney function · Pain ·Excess fluid in body tissues, causing swelling ·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 a
reduction in 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 ·Loss of 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 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 ·Redness of the skin ·Sudden redness of the skin that develops in an
previously irradiated area.

Very rare(may affect up to 1 in 10,000 people):
Skin and soft tissue infection ·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, with cracks 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 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 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 Zentiva

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 after “EXP”. The expiry
date refers to the last day of that month.
This medicine does not require special storage conditions.
Do not freeze.
Diluted solutions: the product must be used immediately.
The chemical and physical stability during use of the pemetrexed infusion solution diluted with 5% dextrose in a
polyvinyl chloride or polyolefin infusion bag and diluted with 0.9% sodium chloride (saline) infusion solution in a
polyvinyl chloride infusion bag has been demonstrated for 24 hours in the dark at refrigerated temperature (from 2 °C to 8 °C).
The chemical and physical stability during use of the pemetrexed infusion solution diluted with 0.9% sodium chloride
(saline) infusion solution in a polyolefin infusion bag has been demonstrated for 3 days in the dark at refrigerated
temperature (from 2 °C to 8 °C).
Chemotherapy syringes - in-use validity and storage conditions:
The chemical and physical stability during use of Pemetrexed 25 mg/ml concentrate for infusion solution
inserted with a chemotherapy syringe into a vial has been demonstrated for 7 days in the dark at
refrigerated temperature (from 2 °C to 8 °C).
This medicine is for single use only, unused solution must be disposed of in
accordance with local legal requirements.

6. Contents of the pack and other information

What Pemetrexed Zentiva contains
The active ingredient is pemetrexed.
A 4 ml vial of concentrate contains 100 mg of pemetrexed (as pemetrexed disarginine).
A 20 ml vial of concentrate contains 500 mg of pemetrexed (as pemetrexed disarginine).
A 40 ml vial of concentrate contains 1,000 mg of pemetrexed (as pemetrexed disarginine).
The solution contains 25 mg/ml of pemetrexed. Further dilution by a
healthcare professional is required before administration.
The other ingredients are L-arginine, L-cysteine, propylene glycol, citric acid and water for
injections.

Description of the appearance of Pemetrexed Zentiva and contents of the pack
Pemetrexed Zentiva is a clear solution, from colourless to slightly yellow or brown, yellow-brown
or yellow-green. It is supplied in glass vials. Each pack contains:
Vial 1 x 4 ml (100 mg / 4 ml)
Vial 1 x 20 ml (500 mg / 20 ml)
Vial 1 x 40 ml (1,000 mg / 40 ml)
The vials are closed with a rubber stopper (bromobutyl), a cap and a flip-off seal.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milan

Manufacturer
Synthon Hispania S.L.
C/Castelló n°1
Pol. Las Salinas, Sant Boi de Llobregat
08830 Barcelona, Spain
Synthon BV
Microweg 22
Nijmegen
6545 CM Netherlands
Synthon s.r.o.
Brnĕnská 32 /čp. 597
Blansko
67801 Czech Republic

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
France Pemetrexed Zentiva 25 mg/ml, solution for infusion
Estonia Pemetrexed Zentiva k.s.
Germany Pemetrexed Zentiva 25 mg/ml Concentrate for the preparation of a solution for infusion
Italy Pemetrexed Zentiva 25 mg/ml
Lithuania: Pemetrexed Zentiva k.s. 25 mg/ml concentrate for solution for infusion
Netherlands Pemetrexed Zentiva 25 mg/ml, concentrate for solution for infusion
Romania Pemetrexed Zentiva 25 mg/ml concentrate for solution for infusion
United Kingdom Pemetrexed Zentiva 25 mg/ml, concentrate for solution for infusion

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

• 1. During the reconstitution and further dilution of pemetrexed for the administration of the intravenous infusion, use aseptic techniques.
• 2. Calculate the dose and the number of vials of Pemetrexed Zentiva needed. Each vial contains an excess of pemetrexed to facilitate dispensing the amount indicated on the label. Each vial contains a solution containing 25 mg/ml of pemetrexed.
• 3. The appropriate volume of the solution must be further diluted to 100 ml with 0.9% sodium chloride solution or 5% dextrose solution, without preservatives, and administered as an intravenous infusion over 10 minutes.
• 4. Infusion solutions of pemetrexed 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 solution for injections and Ringer’s solution for injections. Pemetrexed Zentiva contains L-Arginine as an excipient. L-arginine is incompatible with cisplatin resulting in cisplatin degradation. This medicinal product should not be mixed with other medicinal products. Intravenous lines should be flushed after administration of Pemetrexed Zentiva.
• 5. Before administration, parenteral products should be visually inspected for particulate matter and colour changes. Do not administer if particulate matter is observed.
• 6. Pemetrexed solutions are for single use only. Unused product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations for cytotoxic agents. 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 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. Pemetrexed is not vesicant. There is no specific antidote for pemetrexed extravasation. Some cases of pemetrexed extravasation have been reported which were not considered serious by the investigator. Extravasation should be managed according to standard procedures as for other non-vesicant agents.