Pemetrexed Aurobindo

Package leaflet: Information for the user

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 pack sizes of 100 mg and 500 mg)
Please read all of this leaflet carefully before you take 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 give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including 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 taking 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

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

Pemetrexed Aurobindo is a medicine used in the treatment of cancers.
Pemetrexed Aurobindo 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 Aurobindo, in combination with cisplatin, is administered as first-line therapy
in patients with advanced-stage lung cancer.
Pemetrexed Aurobindo may be prescribed for advanced-stage lung cancer if the disease has responded to
treatment or if it remains mostly unchanged after initial chemotherapy.
Furthermore, Pemetrexed Aurobindo is a treatment for patients with advanced-stage lung cancer whose
disease has progressed after a previous initial chemotherapy treatment.

2. What you should know before taking 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 received or are about to receive the yellow fever vaccine.

Warnings and precautions
Talk to your doctor or hospital pharmacist before receiving Pemetrexed Aurobindo.
Tell your doctor or hospital pharmacist if you have or have had kidney problems, as this may affect whether
you can receive Pemetrexed Aurobindo.
Before each infusion, blood tests will be performed to assess whether your liver and kidney functions are
sufficient and to check that you have enough blood cells to receive Pemetrexed Aurobindo. 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.
Inform your doctor if you have undergone or are scheduled to undergo radiation therapy, as Pemetrexed
Aurobindo may cause an early or delayed reaction related to radiation treatment.
Inform your doctor if you have recently been vaccinated, as this could cause harmful effects when taking
Pemetrexed Aurobindo.
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 remove the fluid before
administering Pemetrexed Aurobindo.

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

Other medicines and Pemetrexed Aurobindo
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 varying durations of action. Depending on the
scheduled date for your Pemetrexed Aurobindo infusion and/or your kidney function, your doctor will advise you
on which medicines you can take and when. If you are unsure, ask your doctor or pharmacist whether any of
your medicines are NSAIDs.
Inform your doctor if you are taking medicines called proton pump inhibitors (omeprazole, esomeprazole,
lansoprazole, pantoprazole and rabeprazole) used to treat heartburn and acid reflux.
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. Use of
Pemetrexed Aurobindo during pregnancy should be avoided. Your doctor will discuss with you the potential
risks 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, inform your doctor.
Breastfeeding must be discontinued during treatment with Pemetrexed Aurobindo.

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

Driving and using machines
Pemetrexed Aurobindo may cause tiredness. Be cautious when driving or operating 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 corresponds to 2.7% of the maximum daily recommended dietary intake for 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 corresponds to 5.4% of the maximum daily recommended dietary intake for an adult.

3. How to take Pemetrexed Aurobindo

The dose of Pemetrexed Aurobindo 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 mixed the Pemetrexed Aurobindo powder with a sodium chloride solution 9 mg/ml (0.9%) for injectable preparations before administering it to you.
You will always receive Pemetrexed Aurobindo by intravenous infusion. The infusion will last approximately 10 minutes.
When Pemetrexed Aurobindo is used in combination with cisplatin:
Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight.
Cisplatin is also administered by intravenous infusion, approximately 30 minutes after the Pemetrexed Aurobindo infusion has been completed. The cisplatin infusion will last approximately 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, the day of, and the day after treatment with Pemetrexed Aurobindo. 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 (350–1000 micrograms) to be taken orally once daily during treatment with Pemetrexed Aurobindo. You must take at least 5 doses during the 7 days prior to your first dose of Pemetrexed Aurobindo. You should continue taking folic acid for 21 days after your last dose of Pemetrexed Aurobindo. You will also receive an injection of vitamin B12 (1000 micrograms) during the week before administration of Pemetrexed Aurobindo, and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Aurobindo). Vitamin B12 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 (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 begin to feel chest pain (common) or have 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 serious and may lead to death. Contact your doctor if a severe rash appears, or if you have itching or blistering (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, reddish or slightly pink urine, or unexpected bruising (because you may have fewer platelets than normal, which is common).
• If you suddenly feel short of breath, have severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the lung vessels).

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.
• Damage to motor nerves which may cause stiffness and muscle atrophy, leading to muscle weakness and primary atrophy (wasting) 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 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.
• Itchy skin.
• Widespread red spots.
• Hair loss.
• Hives.
• Kidneys stop working.
• Reduced kidney function.
• Fever.
• Pain.
• Fluid accumulation 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.
• A type of stroke when an artery in the neck 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, of one of the pulmonary arteries.
• Inflammation and scarring of the lung lining causing breathing problems.
• Bright red bleeding from the anus.
• Gastrointestinal tract bleeding.
• Bowel perforation.
• Inflammation of the oesophageal lining.
• Inflammation of the lining of the large intestine, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin).
• Inflammation, oedema, erythema, 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 condition of the liver.
• 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 may be life-threatening).
• Toxic epidermal necrolysis (a type of severe skin reaction that may be life-threatening).
• Autoimmune disorders resulting in sudden skin redness and blisters on the legs, arms, and abdomen.
• Skin inflammation characterised 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 available data):

• A form of diabetes primarily due to kidney disease.
• Kidney disorders leading to death of tubular epithelial cells that form 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 start experiencing any of these side effects.
If you have any concerns about any side effect, discuss them with your doctor.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via 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 stated on the pack and vial after
EXP. The expiry date refers to the last day of that month.
100 mg: Store below 30°C.
500 mg and 1000 mg: This medicine requires no special storage precautions.
Reconstituted and infusion solutions: the chemical and physical stability of reconstituted pemetrexed solutions for infusion has been demonstrated for 24 hours at 2-8°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and 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 any visible signs of deterioration.
This medicine is for single use only.
Do not dispose of any medicine via 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 Aurobindo contains
The active substance 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 by healthcare personnel is required prior to administration.
The other components are mannitol, hydrochloric acid, and sodium hydroxide.

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

Marketing Authorization 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
Arrow Génériques,
26 Avenue Tony Garnier,
Lyon, 69007
France

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium: Pemetrexed Eugia 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 Eugia
Portugal: Pemetrexed Eugia

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

Instructions for use, handling, and disposal

1. During reconstitution and subsequent dilution of pemetrexed for intravenous infusion administration, use aseptic techniques.
2. Calculate the required dose and number of Pemetrexed Aurobindo vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the labeled amount.
3. Pemetrexed Aurobindo 100 mg: Reconstitute the 100 mg vials with 4.2 ml of 9 mg/ml (0.9%) sodium chloride solution for injection, 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 9 mg/ml (0.9%) sodium chloride solution for injection, 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 9 mg/ml (0.9%) sodium chloride solution for injection, 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 colorless to yellow or yellow-green, which does not negatively affect the product quality. The pH of the reconstituted solution ranges 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 9 mg/ml (0.9%) sodium chloride solution for injection, without preservatives, and administered as a 10-minute intravenous infusion.
5. Pemetrexed infusion solutions prepared as described above are compatible with infusion bags and administration sets lined with polyvinyl chloride and polyolefins. Pemetrexed is incompatible with calcium-containing solvents, including Ringer's lactate solution for injection and Ringer's solution for injection.
6. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. Do not administer if particulate matter is observed.
7. 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.

Storage
The chemical and physical in-use stability of reconstituted and diluted pemetrexed solutions has been demonstrated for 24 hours at 2–8°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature between 2°C and 8°C, unless reconstitution/dilution was performed under controlled 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. Glove use 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. Some 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.