Pemetrexed Glenmark

Package leaflet: Information for the user

Pemetrexed Glenmark 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion

pemetrexed disodium heptahydrate
Equivalent medicine
Please read all of this leaflet carefully before you 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

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

Pemetrexed Glenmark is a medicine used to treat cancers.
Pemetrexed Glenmark is given 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 previously received chemotherapy.
Additionally, Pemetrexed Glenmark, in combination with cisplatin, is used as first-line therapy
in patients with advanced-stage lung cancer.
Pemetrexed Glenmark may be prescribed for advanced-stage lung cancer if the disease has responded to treatment or remains mostly unchanged after initial chemotherapy.
Furthermore, Pemetrexed Glenmark 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 taking Pemetrexed Glenmark

Do not take Pemetrexed Glenmark

• 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 Glenmark.
• if you have recently received or are about to receive the yellow fever vaccination.

Warnings and precautions
Talk to your doctor, hospital pharmacist, or nurse before using Pemetrexed Glenmark.
If you have or have had kidney problems, inform your doctor or hospital pharmacist, as you may not
be able to receive Pemetrexed Glenmark.
Before each infusion, blood tests will be performed to assess whether you have adequate liver and kidney
function and to check that you have enough blood cells to receive Pemetrexed Glenmark. Your doctor may
decide to adjust the dose or delay treatment depending on your general condition and if blood test results
(white blood cells and platelets) are inadequate (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 will undergo radiotherapy, inform your doctor, as Pemetrexed Glenmark may
cause an early or delayed reaction due to radiation therapy.
If you have recently been vaccinated, inform your doctor, as Pemetrexed Glenmark could cause harmful
effects.
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 Glenmark.
Children and adolescents
This medicine must not be used in children and adolescents, as there is no experience with Pemetrexed
Glenmark in individuals under 18 years of age.
Other medicines and Pemetrexed Glenmark
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 over-the-counter medicines (such as
ibuprofen). There are many types of NSAIDs with different durations of action. Depending on the
scheduled date of pemetrexed infusion and/or your kidney function, your doctor will advise you 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.
Inform your doctor or hospital pharmacist if you are taking or have recently taken any other medicines,
including those obtained without a prescription.
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor or
pharmacist before taking this medicine.
The use of Pemetrexed Glenmark during pregnancy should be avoided. Your doctor will discuss with you
the potential risks of taking Pemetrexed Glenmark during pregnancy. Women must use an effective method
of contraception during treatment with Pemetrexed Glenmark 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 Glenmark.
Fertility
Men are advised not to father a child during treatment with Pemetrexed Glenmark and for up to 3 months
after treatment. Therefore, an effective contraceptive method should be used during treatment with
Pemetrexed Glenmark and for 3 months thereafter. If you wish to father a child during treatment or within
3 months after, consult your doctor or pharmacist. Pemetrexed Glenmark may affect your ability to have
children. Talk to your doctor for advice on sperm preservation before starting therapy.
Driving and using machines
Pemetrexed Glenmark may cause fatigue. Be cautious when driving a vehicle or operating machinery.
Pemetrexed Glenmark contains sodium
Pemetrexed Glenmark 100 mg concentrate powder 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 Glenmark 500 mg concentrate powder 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 maximum daily recommended dietary intake of sodium for an adult.

3. How to take Pemetrexed Glenmark

The dose of Pemetrexed Glenmark 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 Glenmark powder with a sodium chloride solution 9 mg/ml (0.9%) for injectable preparations before administering it to you. Pemetrexed Glenmark will always be given by intravenous infusion. The infusion will last approximately 10 minutes.

When Pemetrexed Glenmark is used in combination with cisplatin:
Your doctor or hospital pharmacist will calculate the dose you require based on your height and weight. Cisplatin is also administered by intravenous infusion, approximately 30 minutes after the Pemetrexed Glenmark infusion has been completed. The cisplatin infusion will last about 2 hours. Usually, you will receive the infusion once every 3 weeks.

Additional medicines:

Corticosteroids: Your doctor will prescribe steroid tablets (equivalent to 4 mg of dexamethasone twice daily) to be taken the day before, on the day of, and the day after treatment with Pemetrexed Glenmark. 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 Glenmark. You must take at least 5 doses during the 7 days before your first dose of Pemetrexed Glenmark. You should continue taking folic acid for 21 days after your last dose of Pemetrexed Glenmark. You will also receive an injection of vitamin B₁₂ (1000 micrograms) during the week before administration of Pemetrexed Glenmark, and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Glenmark). 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 start experiencing chest pain (common) or have an increased heart rate (uncommon).
• If you have pain, redness, swelling, or ulcers in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), a burning or tingling sensation (common), or fever (common). Skin reactions are rarely severe and may be life-threatening. Contact your doctor if you develop a severe rash, itching, or a rash with blisters (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, reddish or slightly pink urine, or unexpected bruising (because you may have fewer platelets than normal, which is common).
• If you suddenly develop shortness of breath, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the blood vessels of the lungs).

Side effects with Pemetredex Glenmark 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
Rash
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 reaction
Loss of body fluids
Altered taste
Nerve damage that may cause stiffness and muscle atrophy, leading to muscle weakness and primary atrophy (wasting) in the arms and legs
Sensory nerve damage that may cause loss of sensation, burning pain, 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
Watery eyes
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)
Swelling of the eyelids
Eye disorder with dryness, tearing, irritation, and/or pain
Heart failure (a condition affecting the heart muscle's pumping ability)
Irregular heart rhythm
Indigestion
Constipation
Abdominal pain
Liver: increased levels in the blood 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
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 in the blood
Stroke
Type of stroke when an artery in the neck is blocked
Bleeding within 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
Intestinal rupture
Inflammation of the oesophageal lining
Inflammation of the lining of the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only in combination with cisplatin)
Inflammation, oedema, erythema, and erosion of the oesophageal mucosa surface caused by radiation therapy
Lung inflammation caused by radiotherapy

Rare (may affect up to 1 in 1,000 people)
Destruction of red blood cells
Anaphylactic shock (severe allergic reaction)
Inflammatory liver condition
Skin redness
Sudden skin rash 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 severe type of skin and mucous membrane reaction that may be life-threatening)
Toxic epidermal necrolysis (a severe type of skin reaction that may be life-threatening)
Autoimmune disorders resulting in sudden skin rashes and blisters on the legs, arms, and abdomen
Skin inflammation characterized by the presence of blisters that fill with fluid
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 the available data
A form of diabetes primarily due to kidney disease
Kidney disorders leading to death of tubular epithelial cells forming the renal tubules

You may experience one or more of these symptoms and/or conditions. You must inform your doctor as soon as possible if you experience any of these side effects.
If you have any questions 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 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 Glenmark

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial 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 should be used immediately. If prepared as
instructed, chemical and physical in-use stability of reconstituted pemetrexed solutions for
infusion has been demonstrated for 48 hours under refrigerated conditions.
Do not dispose of any medicine via waste water. Ask your pharmacist how to dispose of medicines no
longer required. This will help protect the environment.

6. Package contents and other information

What Pemetrexed Glenmark contains
The active substance is pemetrexed.
Pemetrexed Glenmark 100 mg: Each vial contains pemetrexed disodium heptahydrate equivalent to
100 mg of pemetrexed.
Pemetrexed Glenmark 500 mg: Each vial contains pemetrexed disodium heptahydrate equivalent to
500 mg of pemetrexed.
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 (E421), hydrochloric acid (to adjust pH), and sodium hydroxide (to adjust pH).

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

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Glenmark Arzneimittel GmbH
Industriestrasse 31
82194 Groebenzell
Germany
Manufacturer
Apis labor GmbH
Resslstrasse 9
9065 Ebenthal in Kaernten
Austria

This medicinal product is authorized in the European Economic Area countries under the following names:
Germany Pemetrexed Glenmark 100 mg powder for concentrate for solution for infusion
Pemetrexed Glenmark 500 mg powder for concentrate for solution for infusion
Spain Pemetrexed Glenmark 100 mg powder for concentrate for perfusion solution
Pemetrexed Glenmark 500 mg powder for concentrate for perfusion solution
Sweden Pemetrexed Glenmark 100 mg powder for concentrate for infusion solution, solution
Pemetrexed Glenmark 500 mg powder for concentrate for infusion solution, solution
Norway Pemetrexed Glenmark 100 mg powder for concentrate for infusion solution, solution
Pemetrexed Glenmark 500 mg powder for concentrate for infusion solution, solution
Denmark Pemetrexed Glenmark
Finland Pemetrexed Glenmark 100 mg dry substance for intermediate concentrate for infusion solution, solution
Pemetrexed Glenmark 500 mg dry substance for intermediate concentrate for infusion solution, solution
Poland Pemetrexed Glenmark
Italy Pemetrexed Glenmark 100 mg powder for concentrate for solution for infusion
Pemetrexed Glenmark 500 mg powder for concentrate for solution for infusion

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

1. Use aseptic techniques during reconstitution and further dilution of pemetrexed for intravenous infusion administration.
2. Calculate the required dose and number of pemetrexed vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the labeled amount.
3. Pemetrexed Glenmark 100 mg: Reconstitute each 100 mg vial with 4.2 ml of sodium chloride solution 9 mg/ml (0.9%) for injection to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed Glenmark 500 mg:
Reconstitute each 500 mg vial with 20 ml of sodium chloride solution 9 mg/ml (0.9%) for injection 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 in colour 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 sodium chloride solution 9 mg/ml (0.9%) 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 coated with polyvinyl chloride and polyolefins. Pemetrexed is incompatible with calcium-containing solvents, including sodium chloride and potassium chloride with glucose, Ringer lactate solution for injection, and Ringer 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 product and waste material must be disposed of in accordance with local legal requirements.

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, rinse thoroughly with water. Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. Cases of pemetrexed extravasation have been reported but were not considered severe by the investigator.
Extravasation should be managed according to standard procedures for non-vesicant agents.