Pemetrexed Mylan: detailed information

Package leaflet: Information for the user

Pemetrexed Mylan 25 mg/ml concentrate for solution for infusion

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

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

What is in this leaflet:

What Pemetrexed Mylan is and what it is used for
What you need to know before being given Pemetrexed Mylan
How Pemetrexed Mylan is given
Possible side effects
How to store Pemetrexed Mylan
Contents of the pack and other information

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

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

2. What you need to know before using Pemetrexed Mylan

Do not use Pemetrexed Mylan

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

Children and adolescents
There is no indication for the specific use of Pemetrexed Mylan in the pediatric population.

Other medicines and Pemetrexed Mylan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription.
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 obtained without a prescription (such as ibuprofen). There are many types of NSAIDs with different durations of action. Depending on the scheduled date for Pemetrexed Mylan infusion and/or your kidney function, your doctor will advise you on which medicines you can take and when you can take them. If you are unsure, ask your doctor or pharmacist whether any of your medicines are NSAIDs.

Pregnancy, breastfeeding and fertility

Pregnancy
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using this medicine.
The use of Pemetrexed Mylan during pregnancy should be avoided. Your doctor will discuss with you the potential risks of taking Pemetrexed Mylan during pregnancy.
Women must use an effective method of contraception during treatment with Pemetrexed Mylan.

Breastfeeding
If you are breastfeeding, inform your doctor.
Breastfeeding must be discontinued during treatment with Pemetrexed Mylan.

Fertility
Men are advised not to father a child during treatment with Pemetrexed Mylan and for up to 6 months afterwards; therefore, an effective contraceptive method should be used during treatment with Pemetrexed Mylan and for 6 months afterwards. If you wish to father a child during treatment or within 6 months afterwards, consult your doctor or pharmacist. It is recommended to seek information on sperm preservation methods before starting therapy.

Driving and use of machines
Pemetrexed Mylan may cause fatigue. Be cautious when driving a vehicle or operating machinery.

3. How to use Pemetrexed Mylan

The dose of Pemetrexed Mylan 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 treatment delayed depending on your blood test results and general condition. A hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Mylan solution with a 5% glucose solution for injectable preparations before administering it to you.
You will always receive Pemetrexed Mylan as an intravenous infusion. The infusion will last approximately 10 minutes.
When Pemetrexed Mylan 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 as an intravenous infusion, approximately 30 minutes after completion of the Pemetrexed Mylan infusion. The cisplatin infusion will last about 2 hours.
You will usually receive the infusion once every 3 weeks.
Additional medicines
Corticosteroids
Your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) to be taken the day before, on the day of, and the day after treatment with Pemetrexed Mylan. 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 Mylan. You must take at least 5 doses during the 7 days before your first dose of Pemetrexed Mylan. You should continue taking folic acid for 21 days after your last dose of Pemetrexed Mylan. You will also receive an injection of vitamin B₁₂ (1000 micrograms) during the week before administration of Pemetrexed Mylan, and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Mylan). 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 everyone gets them.
You must contact your doctor immediately if you notice any of the following side effects:

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

Side effects with Pemetrexed Mylan may include:
Very common side effects (may affect more than 1 in 10 people)

Low white blood cell count
Low haemoglobin levels (anaemia)
Low platelet count
Diarrhoea
Vomiting
Pain, redness, swelling or sores in the mouth
Nausea
Loss of appetite
Fatigue (tiredness)
Rash
Hair loss
Constipation
Loss of sensation
Kidney: abnormal blood tests

Common side effects (may affect up to 1 in 10 people)

Allergic reaction: rash/burning or tingling sensation
Infection including sepsis
Fever
Dehydration
Kidney failure
Skin irritation and itching
Chest pain
Muscle weakness
Conjunctivitis (inflammation of the eyes)
Stomach disorders
Abdominal pain
Taste alteration
Liver: abnormal blood tests
Increased tearing
Increased skin pigmentation

Uncommon side effects (may affect up to 1 in 100 people)

Acute kidney failure
Increased heart rate
Inflammation of the oesophageal wall reported with Pemetrexed Mylan/radiotherapy treatment.
Colitis (inflammation of the inner wall of the colon which may be associated with intestinal or rectal bleeding)
Interstitial pneumonia (small scars around the lung alveoli)
Oedema (excess fluid in body tissues, causing swelling). Some patients have experienced heart attack or stroke, even minor ones, during treatment with Pemetrexed Mylan, usually in association with other anti-cancer therapy.
Pancytopenia – low combined count of white blood cells, red blood cells and platelets.
Radiation pneumonitis (small scars around the lung alveoli, related to radiotherapy) may occur in patients receiving radiotherapy before, during or after Pemetrexed Mylan infusion.
Pain in extremities, low body temperature, and skin colour changes have been reported.
Blood clots in the blood vessels of the lungs (pulmonary embolism).

Rare side effects (may affect up to 1 in 1,000 people)

Radiation recall phenomena (rash resembling severe sunburn) that may occur in areas of skin previously exposed to radiotherapy, from days to years after irradiation.
Blister formation (skin diseases causing blisters) – including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Immune-mediated haemolytic anaemia (anaemia due to destruction of red blood cells).
Hepatitis (inflammation of the liver).
Anaphylactic shock (severe allergic reaction).

Not known: frequency cannot be estimated from the available data

Swelling with pain and redness in the lower limbs.
Increased urine production
Thirst and increased water intake
Hypernatraemia (high levels of sodium in the blood)
Skin inflammation, especially of the lower limbs, with swelling, pain and redness.

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 doubts about any side effect, discuss it with your doctor.
Reporting of side effects
If you get 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 Mylan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after Exp.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not freeze.
Diluted solutions: the product should be used immediately. When prepared according to
the instructions, the chemical and physical stability during use of diluted pemetrexed solutions has
been demonstrated for 24 hours under refrigerated conditions. Protect from light.
This medicine is for single use only. Any unused solution must be disposed of in accordance with local regulations.

6. Package contents and other information

What Pemetrexed Mylan contains
The active substance is pemetrexed.
Each 4 ml vial of concentrate contains 100 mg of pemetrexed (as pemetrexed diarginine).
Each 20 ml vial of concentrate contains 500 mg of pemetrexed (as pemetrexed diarginine).
Each 40 ml vial of concentrate contains 1000 mg of pemetrexed (as pemetrexed diarginine).
The solution contains 25 mg/ml of pemetrexed. Further dilution by healthcare personnel is required prior to administration.
The other components are L-arginine, L-cysteine, propylene glycol, citric acid, and water for injections.

Description of the appearance of Pemetrexed Mylan and contents of the pack
Pemetrexed Mylan is a clear solution ranging from colourless to light yellow, brownish, yellow-brown to yellow-green. It is supplied in glass vials. Each pack contains:
1 vial of 4 ml (100 mg/4 ml)
1 vial of 20 ml (500 mg/20 ml)
1 vial of 40 ml (1000 mg/40 ml)
The vials are closed with a rubber stopper (bromobutyl) and an aluminium flip-off seal.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Mylan S.p.A., Via Vittor Pisani, 20, 20124 Milano, Italy

Manufacturer
Synthon Hispania SL, C/ Castelló no1, Pol. Las Salinas, Sant Boi de Llobregat, Barcelona 08830, Spain
Synthon BV, Microweg 22, Nijmegen 6545 CM, The Netherlands
Synthon, s.r.o., Brněnská 32/čp. 597, Blansko 678 01, Czech Republic

The following information is intended exclusively for healthcare professionals:

Instructions for use, handling, and disposal

During dilution of pemetrexed for intravenous infusion administration, use aseptic techniques.
Calculate the required dose and number of Pemetrexed Mylan vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the labeled amount. Each vial contains a solution with 25 mg/ml of pemetrexed.
The appropriate volume of solution must be further diluted to 100 ml with 5% dextrose solution for injection, without preservatives, and administered as an intravenous infusion over 10 minutes.
Pemetrexed infusion solutions prepared as described above are compatible with infusion bags and administration sets coated with polyvinyl chloride and polyolefins. Pemetrexed is incompatible with diluents containing calcium, including Ringer's lactate for injectable preparations and Ringer's solution for injectable preparations.

Pemetrexed Mylan contains L-arginine as an excipient. L-arginine is incompatible with
cisplatin due to degradation of cisplatin. This medicinal product must not be mixed with other medicinal products. Intravenous infusion lines must be flushed
after administration of Pemetrexed Mylan.

Prior to administration, parenteral medicinal products must be visually inspected for the presence of particles and discoloration. Do not administer if particles are observed.
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 governing 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. Use of gloves is recommended. If a pemetrexed solution comes into contact with the skin, wash immediately and thoroughly with soap and water. If pemetrexed solutions come into contact with mucous membranes, rinse thoroughly with water. Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. Cases of pemetrexed extravasation have been reported, which were not considered severe by the investigator. Extravasation should be managed according to standard procedures for non-vesicant agents.