Pemetrexed glenmark

Package leaflet: Information for the user

Pemetrexed Glenmark, 100 mg, powder for preparation of concentrate for infusion solution
Pemetrexed Glenmark, 500 mg, powder for preparation of concentrate for infusion solution
Pemetrexedum
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents

1. What Pemetrexed Glenmark is and what it is used for
2. Important information before using 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 in the treatment of malignant tumours.
Pemetrexed Glenmark, in combination with cisplatin, another anticancer medicine, is used to treat malignant pleural mesothelioma, a type of cancer affecting the membrane covering the lungs, in patients who have not previously received chemotherapy.
Pemetrexed Glenmark in combination with cisplatin is used as first-line treatment in patients with advanced lung cancer.
Pemetrexed Glenmark may be prescribed to patients with advanced stage lung cancer who have responded to initial chemotherapy or whose disease has remained largely stable following initial chemotherapy.
Pemetrexed Glenmark is also used to treat patients with advanced stage lung cancer in whom the disease has progressed after initial chemotherapy.

2. Important information before using Pemetrexed Glenmark

When not to use Pemetrexed Glenmark

• if the patient is allergic to pemetrexed or to any of the other ingredients of this medicine (listed in section 6);
• if the patient is breastfeeding; breastfeeding must be discontinued during treatment with Pemetrexed Glenmark;
• in patients who have recently been vaccinated or are scheduled to be vaccinated against yellow fever.

Warnings and precautions
Before starting treatment with Pemetrexed Glenmark, discuss this with your doctor, hospital pharmacist, or nurse.
If the patient currently has or has previously had kidney problems, consult a doctor or hospital pharmacist, as Pemetrexed Glenmark may not be allowed.
Before each infusion, medical staff will take blood samples from the patient to assess whether liver and kidney function are normal and whether there is an adequate number of blood cells to allow administration of Pemetrexed Glenmark. The doctor may decide to adjust the dose or delay treatment depending on the patient's general condition and low blood cell counts. If the patient is also receiving cisplatin, the doctor will ensure that the patient is adequately hydrated and will administer appropriate treatment before and after receiving cisplatin to prevent vomiting.
If the patient has undergone or will undergo radiotherapy, inform the doctor, as early or delayed radiation reactions may occur after administration of Pemetrexed Glenmark.
If the patient has recently been vaccinated, inform the doctor, as adverse reactions may occur after administration of Pemetrexed Glenmark.
If the patient has or has had heart disease, inform the doctor.
If fluid accumulates around the patient's lungs, the doctor may decide to perform a procedure to remove the fluid before administering Pemetrexed Glenmark.

Children and adolescents
This medicine must not be used in children and adolescents due to lack of experience with its use in patients under 18 years of age.

Pemetrexed Glenmark and other medicines
Inform the doctor about all pain-relieving and anti-inflammatory medicines (medicines that reduce swelling) being taken, including non-steroidal anti-inflammatory drugs (NSAIDs), even those available without a prescription (e.g. ibuprofen). There are many types of non-steroidal anti-inflammatory drugs (NSAIDs) with different durations of action. Depending on the planned date of Pemetrexed Glenmark infusion and/or the patient's kidney function, the doctor will advise which medicines can be taken and when. If in doubt whether a medicine belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs), ask the doctor or pharmacist.
Inform the doctor if the patient is taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lanzoprazole, pantoprazole, and rabeprazole) used to treat heartburn and acid reflux.
Inform the doctor or hospital pharmacist if the patient is taking or has recently taken any other medicines, including those available without a prescription.

Pregnancy
If the patient is pregnant, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Pemetrexed Glenmark must not be used during pregnancy. The doctor will inform the patient about the possible risks associated with using the medicine during pregnancy. Women must use an effective method of contraception during treatment with Pemetrexed Glenmark and for 6 months after the last dose.

Breastfeeding
If the patient is breastfeeding, inform the doctor.
Breastfeeding must be discontinued during treatment with Pemetrexed Glenmark.

Fertility
Men are advised not to attempt to father a child during treatment and for 3 months after completion of treatment with Pemetrexed Glenmark. Men should use effective contraception during treatment with Pemetrexed Glenmark and for 3 months after treatment ends. If a man wishes to father a child during treatment with Pemetrexed Glenmark or within 3 months after treatment ends, he should seek advice from his doctor or pharmacist. Pemetrexed Glenmark may affect the ability to have children. Before starting treatment, patients may consult their doctor about sperm preservation.

Driving and operating machinery
Pemetrexed Glenmark may cause fatigue. Exercise caution when driving or operating machinery.

Pemetrexed Glenmark contains sodium
Pemetrexed Glenmark 100 mg, powder for concentrate for infusion solution
This medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".
Pemetrexed Glenmark 500 mg, powder for concentrate for infusion solution
This medicine contains 54 mg of sodium (a main component of table salt) in each vial. This corresponds to 2.7% of the maximum recommended daily intake of sodium for adults.

3. How to use Pemetrexed Glenmark

The dose of Pemetrexed Glenmark is 500 milligrams per square metre of the patient's body surface area. The patient's body surface area is calculated based on measurements of height and weight. The physician will determine the dose of the medicine according to the calculated body surface area. This dose may be adjusted or treatment may be delayed depending on blood cell counts and the patient's general condition. Prior to administration, the hospital pharmacist, nurse, or physician will reconstitute the powder with 9 mg/ml (0.9%) sodium chloride solution for injection.
Pemetrexed Glenmark is always administered as an intravenous infusion. The infusion will last approximately 10 minutes.

Administration of Pemetrexed Glenmark together with cisplatin:
The physician or hospital pharmacist will calculate the dose based on the patient's height and weight. Cisplatin is also administered as an intravenous infusion and is given approximately 30 minutes after completion of the Pemetrexed Glenmark infusion. The cisplatin infusion will last about 2 hours.
Infusions are usually administered once every 3 weeks.

Additional medications:

Corticosteroids: Your doctor will prescribe steroid tablets (in a dose equivalent to 4 milligrams of dexamethasone twice daily) to be taken on the day before, the day of, and the day after the infusion of Pemetrexed Glenmark. This medication is used to reduce the frequency and severity of skin reactions that may occur during anticancer therapy.

Vitamin supplementation: Your doctor will prescribe oral folic acid (vitamin) or a multivitamin product containing folic acid (350 to 1000 micrograms), to be taken once daily during treatment with Pemetrexed Glenmark. At least five doses of folic acid should be taken during the seven days preceding the first dose of Pemetrexed Glenmark. Folic acid supplementation should continue for 21 days after the last dose of Pemetrexed Glenmark. In the week prior to the first administration of Pemetrexed Glenmark, and then at intervals of approximately 9 weeks (corresponding to three cycles of chemotherapy with Pemetrexed Glenmark), patients will also receive vitamin B({12}) (1000 micrograms) by injection. Vitamin B({12}) and folic acid are administered to reduce potential adverse effects of anticancer drugs.

If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following symptoms occur, you should inform your doctor immediately:

• Fever or infection (appropriately often or very often): if the patient develops a fever of 38°C or higher, sweating, or other signs of infection (because the patient may have fewer white blood cells than usual, which is very common). Infection (sepsis) may be severe and lead to death.
• If the patient begins to experience chest pain (often) or rapid heartbeat (not very often).
• If the patient develops pain, redness, swelling or ulcers in the mouth (very often).
• Hypersensitivity reaction: if the patient develops a skin rash (very often), or a burning or stinging sensation (often), or fever (often). Rarely, skin reactions may be severe and lead to death. Inform your doctor if the patient develops severe rash, itching or blisters (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If the patient experiences fatigue, fainting, shortness of breath or paleness (because the patient may have lower hemoglobin levels than normal, which is very common).
• If the patient experiences bleeding from gums, nose or mouth, or any bleeding that cannot be stopped, red or pink discoloration of urine, unexpected bruising (because the patient may have lower platelet count than normal, which is common).
• If the patient suddenly develops shortness of breath, severe chest pain or cough with bloody sputum (not very often) (these may indicate a blood clot in the blood vessels of the lungs).

Adverse reactions of Pemetrexed Glenmark may include:
Very common (may occur in more than 1 in 10 people)
Infection
Sore throat (pharyngitis)
Low neutrophil count (a type of white blood cell)
Low white blood cell count
Low hemoglobin levels
Pain, redness, swelling or ulcers in the mouth
Loss of appetite
Vomiting
Diarrhea
Nausea
Skin rash
Skin desquamation (peeling)
Abnormal blood test results indicating worsening kidney function
Fatigue (tiredness)

Common (may occur in up to 1 in 10 people)
Blood infection
Fever with low neutrophil count (a type of white blood cell)
Low platelet count
Hypersensitivity reaction
Dehydration
Taste disturbances
Damage to motor nerves, which may lead to muscle weakness and atrophy (wasting), mainly in arms and legs
Damage to sensory nerves, which may lead to 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)
Eyelid swelling
Eye disorders with dryness, watering, irritation and (or) pain
Heart failure (a condition causing weakened pumping ability of the heart muscle)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increased blood levels of chemicals produced in the liver
Increased skin pigmentation
Itchy skin
Skin rash with target-like lesions resembling a bull's eye
Hair loss
Urticaria (hives)
Kidney shutdown
Worsening kidney function
Fever
Pain
Excessive fluid in body tissues causing swelling
Chest pain
Inflammation and ulceration of the mucous membranes lining the gastrointestinal tract

Uncommon (may occur in up to 1 in 100 people)
Decreased number of red blood cells, white blood cells and platelets
Stroke
A type of stroke caused by blockage of an artery supplying blood to the brain
Intracranial hemorrhage
Angina (chest pain caused by reduced blood flow to the heart)
Heart attack
Narrowing or blockage of coronary arteries
Rapid heartbeat
Inadequate blood flow to limbs
Blockage of one of the pulmonary arteries in the patient's lungs
Inflammation and scarring of the membrane lining the lungs, causing breathing problems
Bright red blood discharge from the anus
Gastrointestinal bleeding
Intestinal wall rupture
Inflammation of the membrane lining the esophagus
Inflammation of the membrane lining the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only when used in combination with cisplatin)
Inflammation, swelling, redness and erosions of the mucous membrane of the esophagus caused by radiotherapy
Radiation-induced lung inflammation

Rare (may occur in up to 1 in 1,000 people):
Hemolysis (breakdown of red blood cells)
Anaphylactic shock (severe allergic reaction)
Inflammation of the liver
Skin redness
Rash appearing on the skin in previously irradiated areas

Very rare (may occur in up to 1 in 10,000 people)
Skin and soft tissue infections
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 causing rash and blistering skin lesions on legs, arms and abdomen
Skin inflammation characterized by fluid-filled blisters
Fragile skin, presence of blisters and erosions, and skin scarring
Redness, pain and swelling, mainly in the lower limbs
Inflammation of the skin and subcutaneous fat tissue (erythema nodosum-like reaction)
Skin inflammation (dermatitis)
Skin inflammation, itching, redness, cracking and roughness
Severely itchy skin lesions

Frequency not known (frequency cannot be estimated from available data)
Diabetes mellitus mainly caused by kidney disease
Kidney disorders leading to necrosis of renal tubular epithelial cells

Any of these symptoms and (or) diseases may occur in the patient. If any of these adverse reactions occur, you should inform your doctor as soon as possible.
Inform your doctor if you are concerned about any of these symptoms.

Reporting of adverse reactions
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to collect more information on the safety of this medicine.
Adverse reactions can also be reported to the marketing authorization holder.

5. How to store Pemetrexed Glenmark

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after EXP. The expiry date refers to the last day of the stated month.
There are no special storage requirements for this medicine.
Reconstituted solutions for infusion: the product should be used immediately. Chemical and physical stability of pemetrexed solutions for infusion, reconstituted according to the instructions, has been demonstrated for 48 hours when stored refrigerated.
Medicines must not be disposed of via the sewage system. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack 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. Prior to administration, further dilution must be performed by a healthcare professional.
The other ingredients are mannitol (E421), hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment).

What Pemetrexed Glenmark looks like and contents of the pack
Pemetrexed Glenmark is a powder for concentrate solution for infusion, supplied in a vial.
It is a white to pale yellow or greenish-yellow lyophilized cake or powder.

Pack sizes available:
Available in packs of 1 vial in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2b
140 78 Prague 4
Czech Republic

Manufacturer/Importer
Apis Labor GmbH
Resslstrasse 9
Zell
Ebenthal In Kaernten
9065 Austria

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany: Pemetrexed Glenmark 100 mg Powder for a concentrate for solution for infusion
Pemetrexed Glenmark 500 mg Powder for a 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 powder for concentrate for infusion solution, solution
Pemetrexed Glenmark 500 mg powder for concentrate for infusion solution, solution
Poland: Pemetrexed Glenmark
Italy: Pemetrexed Glenmark 100 mg powder for concentrate for infusion solution
Pemetrexed Glenmark 500 mg powder for concentrate for infusion solution

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Glenmark Pharmaceuticals Sp. z o.o.
ul. Dziekonińskiego 3
00-728 Warsaw
Email: [email protected]

Information intended exclusively for healthcare professionals:

Instructions for preparation, administration, and disposal of the drug.

1. Reconstitution and subsequent dilution of the pemetrexed infusion solution must be performed under aseptic conditions.
2. Calculate the required dose and number of vials of Pemetrexed Glenmark. Each vial contains slightly more pemetrexed than stated, which facilitates delivery of the amount indicated on the label.
3. Pemetrexed Glenmark, 100 mg
   Reconstitute the contents of the 100 mg vial with 4.2 ml of sodium chloride injection solution at a concentration of 9 mg/ml (0.9%), to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed Glenmark, 500 mg
Reconstitute the contents of the 500 mg vial with 20 ml of sodium chloride injection solution at a concentration of 9 mg/ml (0.9%), to obtain a solution containing 25 mg/ml of pemetrexed.
Each vial should be gently rotated until the powder is completely dissolved. The resulting solution is clear, colorless to yellow or greenish-yellow, which does not affect the quality of the product. The pH of the reconstituted solution ranges from 6.6 to 7.8. The solution must be further diluted.

4. The appropriate volume of the reconstituted pemetrexed solution should be further diluted to a final volume of 100 ml using sodium chloride injection solution at a concentration of 9 mg/ml (0.9%) without preservatives, and administered as a 10-minute intravenous infusion.
5. Infusion solutions of pemetrexed prepared as described above are compatible with infusion sets and infusion bags whose inner layer is made of polyvinyl chloride and polyolefin.
6. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If visible particulate matter is present in the solution, the drug should not be administered.
7. Pemetrexed solutions are for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

Precautions during preparation and administration of the drug: As with other potentially toxic antineoplastic agents, caution should be exercised when handling the drug and preparing pemetrexed infusion solutions. The use of gloves is recommended. In case of contact of pemetrexed solution with the skin, the skin should be washed immediately and thoroughly with soap and water. In case of contact with mucous membranes, the affected area should be thoroughly rinsed with water. Pemetrexed is not a vesicant. There is no known specific antidote in the event of extravasation of pemetrexed. Several cases of pemetrexed extravasation have been reported, which were not considered serious by investigators. In case of extravasation, manage according to established guidelines, as with other non-vesicant substances.