PEMETREXED 100 mg Proszek Do Sporządzania Roztworu Do Infuzji

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1. Pemetrexed Aurobindo 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion, 1000 mg powder for concentrate for solution for infusion
   1. What is Pemetrexed Aurobindo and what is it used for
   2. What you need to know before you take Pemetrexed Aurobindo
   3. How to take Pemetrexed Aurobindo
   4. Possible side effects
   5. How to store Pemetrexed Aurobindo
   6. Contents of the pack and other information

Pemetrexed Aurobindo 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion, 1000 mg powder for concentrate for solution for infusion

Equivalent medicinal product (for 100 mg and 500 mg packs)

Read this leaflet carefully before you start to use 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• 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 Aurobindo is and what it is used for
• 2. What you need to know before you are given Pemetrexed Aurobindo
• 3. How Pemetrexed Aurobindo is given
• 4. Possible side effects
• 5. How to store Pemetrexed Aurobindo
• 6. Contents of the pack and other information

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

Pemetrexed Aurobindo is a medicine used in the treatment of tumors.
Pemetrexed Aurobindo is administered in association with cisplatin, another anti-cancer drug, as
treatment for malignant pleural mesothelioma, a form of cancer that affects the lining tissue
of the lungs, in patients who have not received previous chemotherapy.
Furthermore, Pemetrexed Aurobindo, in association with cisplatin, is administered for first-line therapy in
patients affected by advanced stage lung cancer.
Pemetrexed Aurobindo 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 Aurobindo 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 Aurobindo

Do not take Pemetrexed Aurobindo:

• 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 Aurobindo;
• 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 receiving Pemetrexed Aurobindo.
If you have or have had kidney problems, tell your doctor or hospital pharmacist as you may not
be able to receive Pemetrexed Aurobindo.
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 Aurobindo. The doctor may decide to change the dose or delay treatment depending on
your general condition and if the blood test (white blood cells and platelets) 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 having radiation treatment, tell your doctor, as with
Pemetrexed Aurobindo, an early or delayed reaction due to radiation treatment may occur.
If you have been vaccinated recently, tell your doctor, as with Pemetrexed Aurobindo this
may cause harmful effects.
If you have heart disease or a history of heart disease, tell your doctor.
If you have a build-up of fluid around your lungs, the doctor may decide to remove the fluid
before giving you Pemetrexed Aurobindo.

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 Aurobindo
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 bought without a prescription (such as ibuprofen). There are many types of NSAIDs with different
duration of action. Based on the planned date for the Pemetrexed Aurobindo infusion 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 not
sure, ask your doctor or pharmacist if any of your medicines are NSAIDs.
Tell your doctor or hospital pharmacist if you are taking or have recently taken any other
medicines, even those without a prescription.

Pregnancy
If you are pregnant, if you suspect you are pregnant or are planning a pregnancy, tell your doctor. The use of
Pemetrexed Aurobindo during pregnancy should be avoided. The doctor will talk to you about the potential
risk of taking Pemetrexed Aurobindo during pregnancy. Women must use an effective method
of contraception during treatment with Pemetrexed Aurobindo 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 Aurobindo.

Fertility
Men are advised not to father a child during treatment with Pemetrexed Aurobindo until 3
months afterwards and therefore to use effective contraception during treatment with Pemetrexed Aurobindo
and for 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 Aurobindo may affect your ability to
have children. Talk to your doctor for advice on ways to preserve sperm before
starting therapy.

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

Pemetrexed Aurobindo contains sodium
Pemetrexed Aurobindo 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 Aurobindo 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 is equivalent to 2.7% of the recommended maximum daily intake with the diet of an adult.
Pemetrexed Aurobindo 1000 mg powder for concentrate for solution for infusion
This medicine contains 108 mg of sodium (the main component of table salt) per vial.
This is equivalent to 5.4% of the recommended maximum daily intake with the diet of an adult.

3. How to take Pemetrexed Aurobindo

The dose of Pemetrexed Aurobindo 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, a nurse or a doctor will have mixed the powder of Pemetrexed Aurobindo with a solution of sodium chloride 9 mg/ml (0.9%) for injectable preparations before administering it to you.
You will receive Pemetrexed Aurobindo always by infusion into a vein. The infusion will last approximately 10 minutes.
When Pemetrexed Aurobindo is used in combination with cisplatin:
The doctor or the hospital pharmacist will calculate the dose you need based on your height and weight.
Cisplatin is also administered by infusion into a vein, approximately 30 minutes after the Pemetrexed Aurobindo 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 Aurobindo. 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 Aurobindo. You must take at least 5 doses during the seven days before the first dose of Pemetrexed Aurobindo. You must continue to take folic acid for 21 days after the last dose of Pemetrexed Aurobindo. You will also receive an injection of vitamin B12 (1000 micrograms) in the week before the administration of Pemetrexed Aurobindo and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Aurobindo). 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 everyone gets 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 may lead to death.
• If you begin to experience chest pain (common) or 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 may 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 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 (uncommon) (may indicate a blood clot in the pulmonary blood vessels).

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).
• Few 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.
• Scaling of the skin.
• Abnormal blood tests showing reduced kidney function.
• Fatigue (tiredness).

Common(may affect up to 1 in 10 people):

• Bloodstream infection.
• Fever with a 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 stiffness and muscle atrophy that 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 of the eye).
• Dry eye.
• Excessive tearing.
• Dryness of the conjunctiva (the membrane that lines the eyelids and covers the white 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'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.
• Itching of the skin.
• 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.
• 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 a previously irradiated area.

Very rare(may affect up to 1 in 10,000 people):

• Infection of the skin and soft tissues.
• Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that can be life-threatening).
• Toxic epidermal necrolysis (a type of severe skin reaction that can be 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 underlying fat (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):

• 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 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 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 Aurobindo

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 packaging and vial after
EXP. The expiry date refers to the last day of that month.

100 mg: Store at a temperature below 30°C.

500 mg and 1000 mg: This medicine does not require any special storage precautions.
Reconstituted and infusion solutions: the chemical and physical stability of reconstituted and
infusion pemetrexed solutions has been demonstrated for 24 hours at 2-8°C. From a microbiological point of view, the product must
be used immediately. If not used immediately, the storage times of the product in
use and the conditions prior to use are the responsibility of the user and should not exceed 24 hours
at a temperature between 2°C and 8°C.
Do not use this medicine if you notice visible signs of deterioration.
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 Aurobindo contains
The active ingredient is pemetrexed.
Pemetrexed Aurobindo 100 mg: Each vial contains 100 mg of pemetrexed (as pemetrexed
disodium).
Pemetrexed Aurobindo 500 mg: Each vial contains 500 mg of pemetrexed (as pemetrexed
disodium).
Pemetrexed Aurobindo 1000 mg: Each vial contains 1000 mg of pemetrexed (as pemetrexed
disodium).
After reconstitution, the solution contains 25 mg/ml of pemetrexed. Further dilution is
required by healthcare professionals before administration.
The other ingredients are mannitol, hydrochloric acid and sodium hydroxide.

Description of the appearance of Pemetrexed Aurobindo and contents of the pack
Powder for concentrate for solution for infusion.
Lyophilized powder ranging in colour from white to pale yellow or yellow-green.
It is available in packs of 1 vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront,
Floriana FRN 1914, Malta

Manufacturer
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate,
Hal Far, Birzebbugia, BBG 3000
Malta
Generis Farmacȇutica, S.A.
Rua Joao De Deus, no 19,
Venda Nova, 2700-487 Amadora
Portugal
Arrow Génériques,
26 Avenue Tony Garnier,
Lyon, 69007
France

This medicinal product is authorised in the Member States of the European Economic Area with the following
denominations:
Belgium: Pemetrexed AB 500 mg/ 1000 mg poeder voor concentraat voor oplossing voor infusie /
poudre pour solution à diluer pour perfusion / Pulver für ein Konzentrat zur Herstellung
einer Infusionslösung
Denmark: Pemetrexed Aurobindo
France: Pemetrexed Arrow 100 mg/500 mg/1000 mg poudre pour solution à diluer pour perfusion
Germany: Pemetrexed PUREN 100 mg/ 500 mg/ 1000 mg Pulver zur Herstellung eines
Konzentrates zur Herstellung einer Infusionslösung
Italy: Pemetrexed Aurobindo
Poland: Pemetrexed Aurovitas
Portugal: Pemetrexed Generis
Romania: Pemetrexed Aurobindo 500 mg pulbere pentru concentrat pentru soluţie perfuzabilă
Spain: Pemetrexed Aurovitas 100 mg/500 mg polvo para concentrado para solución para
perfusión EFG
Pemetrexed Aurovitas 1.000 mg polvo para concentrado para solución para perfusión

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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 Aurobindo needed. Each vial contains an excess of pemetrexed to facilitate dispensing the amount indicated on the label.
• 3. Pemetrexed Aurobindo 100 mg: Reconstitute the 100 mg vials with 4.2 ml of sodium chloride 9 mg/ml (0.9%) solution for injections, without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed Aurobindo 500 mg:
Reconstitute the 500 mg vials with 20 ml of sodium chloride 9 mg/ml (0.9%) solution for
injections, without preservatives, to obtain a solution containing 25 mg/ml of
pemetrexed.
Pemetrexed Aurobindo 1000 mg:
Reconstitute the 1000 mg vials with 40 ml of sodium chloride 9 mg/ml (0.9%) solution for
injections, without preservatives, to obtain a solution containing 25 mg/ml of
pemetrexed.
Gently swirl each vial until the powder is completely dissolved. The
resulting solution is clear and ranges from colourless to yellow or yellow-green without negatively
affecting the product quality. 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 a sodium chloride 9 mg/ml (0.9%) solution for injections, without preservatives and administered by intravenous infusion over 10 minutes.
• 5. 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 injections and Ringer's solution for injections.
• 6. Before administration, parenteral medicines should be visually inspected for the presence of particles and colour changes. Do not administer if particles are observed.
• 7. Pemetrexed solutions are for single use only. Unused medicine and waste materials derived from such medicine should be disposed of in accordance with local regulations.

Storage
The chemical and physical stability during use of reconstituted and infusion solutions of pemetrexed has been
demonstrated for 24 hours at 2-8°C.
From a microbiological point of view, the product should be used immediately. If not used
immediately, the storage times and conditions before use are the responsibility of the user and
should normally not exceed 24 hours at a temperature between 2°C and 8°C, unless the
reconstitution/dilution has been carried out in a controlled environment and validated aseptic conditions.

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 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 that were not considered severe by the investigator.
Extravasation should be managed according to standard procedures as for other non-vesicant agents.