ARMISARTE 25 mg/mL concentrate for infusion solution

Introduction

Package Leaflet: Information for the User

Armisarte 25 mg/ml concentrate for solution for infusion

pemetrexed

Read all of this leaflet carefully before you start receiving 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 or pharmacist.
• If you experience any side effects, talk to your doctor, nurse or pharmacist, even if it is not listed in this leaflet. See section 4.

Contents of the pack

1. What is Armisarte and what is it used for
2. What you need to know before using Armisarte

1. How to use Armisarte
2. Possible side effects
3. Storage of Armisarte

1. Contents of the pack and further information

1. What is Armisarte and what is it used for

Armisarte is a medicine used to treat cancer that contains the active substance pemetrexed. Pemetrexed belongs to a group of medicines known as "folinic acid analogues" and disrupts processes that are essential for cell division.

Armisarte can be given with cisplatin, another anticancer medicine, as a treatment for malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received chemotherapy before.

Armisarte can also be given, along with cisplatin, for the initial treatment of patients with advanced stages of lung cancer.

Armisarte may be prescribed for you if you have advanced lung cancer, if your disease has responded to treatment or if it remains unchanged after initial chemotherapy.

Armisarte can also be given for the treatment of patients with advanced stages of lung cancer whose disease has progressed, who have already received other initial chemotherapy treatment.

2. What you need to know before using Armisarte

Do not use Armisarte

• if you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).

• if you are breastfeeding, you must stop breastfeeding during treatment with Armisarte.
• if you have recently been given or are going to be given the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or hospital pharmacist before you are given Armisarte.

If you have had or have kidney problems, tell your doctor or hospital pharmacist, as you may not be able to receive Armisarte.

Before each infusion, you will need to give blood samples to check if your kidney and liver function is sufficient and to check if you have enough blood cells to receive Armisarte. Your doctor may decide to change your dose or delay treatment depending on your general condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will make sure you are properly hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are going to receive radiotherapy, please consult your doctor, as an early or late reaction may occur between radiation and Armisarte.

If you have been vaccinated recently, please consult your doctor, as this may cause a negative effect with Armisarte.

If you have a heart condition or a history of heart disease, please consult your doctor.

If you have fluid accumulated around the lung, your doctor may decide to drain the fluid before administering Armisarte.

Children and adolescents

This medicine must not be used in children or adolescents, as there is no experience with this medicine in children and adolescents under 18 years.

Using Armisarte with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines for pain or inflammation (swelling), such as non-steroidal anti-inflammatory medicines (NSAIDs), including those bought without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your Armisarte infusion and/or the status of your kidney function, your doctor will advise which medicines you can use and when you can take them. If you are unsure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

As with other chemotherapy medicines, the use of Armisarte with live vaccines is not recommended. Inactivated vaccines should be used whenever possible.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, tellyour doctor. Armisarte should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking Armisarte during pregnancy. Women must use effective contraceptive methods during treatment with Armisarte.

Breastfeeding

If you are breastfeeding, tell your doctor.

During treatment with Armisarte, breastfeeding should be stopped.

Fertility

Male patients are advised not to father a child during and up to 6 months after treatment with Armisarte, and must use effective contraceptive methods during and up to 6 months after treatment with Armisarte. If you wish to have a child during treatment or in the 6 months following treatment, seek advice from your doctor or pharmacist. You may want to ask about sperm preservation before starting your treatment.

Driving and using machines

Armisarte may make you feel tired. Be careful when driving a vehicle or using machines.

3. How to use Armisarte

Armisarte 25 mg/ml concentrate for solution for infusion will always be given to you by a healthcare professional. The dose of Armisarte is 500 milligrams per square meter of your body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this surface area to calculate the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell count and your general condition. The hospital pharmacist, nurse or doctor will have mixed Armisarte with a 5% glucose solution for injection or sodium chloride 0.9% solution for injection before it is given to you.

You will always receive Armisarte through an infusion (drip) in one of your veins. The infusion will last at least 10 minutes.

When using Armisarte in combination with cisplatin:

Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also given through an infusion in one of your veins and is given about 30 minutes after the Armisarte infusion has finished. The cisplatin infusion lasts about 2 hours.

You should normally receive your infusion once every 3 weeks.

Additional medication:

Corticosteroids: your 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 Armisarte. Your doctor gives you this medicine to reduce the frequency and severity of skin reactions that you may experience during your cancer treatment.

Vitamin supplement: your doctor will prescribe oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms) that you must take once a day while you are taking Armisarte. You must take at least 5 doses during the 7 days before the first dose of Armisarte. You must continue taking folic acid during the 21 days after the last dose of Armisarte. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before Armisarte is given and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Armisarte). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

During treatment, your disease will be closely monitored, which involves regular blood tests to check, among other things, liver and kidney function. Depending on the results of these tests, your dose may be changed or your treatment may be postponed.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

You must tell your doctor immediately if you notice any of the following symptoms:

• Fever or infection (common): if you have a 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). Infections (sepsis) can be serious and life-threatening.

• If you start to feel chest pain (common) or your heart rate is faster (uncommon).
• If you have pain, redness, swelling or sores in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), burning sensation or itching (common) or fever (common). In rare cases, skin reactions can be serious and life-threatening. Contact your doctor if you experience a severe rash, itching or blisters (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you are short of breath or are pale (because you 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 stop, red or pink urine or unexpected bruising (because you have fewer platelets than normal, which is very common).

• If you experience sudden difficulty breathing, severe chest pain or coughing up blood in your sputum (uncommon) (may indicate that there is a blood clot in the lungs).

Other side effects with Armisarte may include:

Very common (may affect more than 1 in 10 people)

• Infection
• Pharyngitis (sore throat)

• Low neutrophil count (a type of white blood cell)
• Low white blood cell count

• Low hemoglobin levels
• Pain, redness, swelling or sores in the mouth
• Loss of appetite

• Vomiting
• Diarrhea

• Nausea
• Rash
• Scaly skin

• Changes in blood tests that show reduced kidney function
• Asthenia (tiredness)

Common (may affect up to 1 in 10 people)

• Blood infection

• Fever with low neutrophil count (a type of white blood cell)
• Low platelet count

• Allergic reaction
• Loss of body fluids
• Changes in taste

• Nerve damage that can cause muscle weakness and wasting (mainly in arms and legs)

• Nerve damage that can cause loss of sensation, burning (pain) and unsteady walking
• Dizziness

• Inflammation or swelling of the conjunctiva (membrane that covers the eyelids and the white part of the eye)
• Dry eyes
• Watery eyes
• Dryness of the conjunctiva (inner membrane of the eyelids) and the cornea (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 that affects the heart's pumping ability)
• Irregular heartbeat

• Indigestion
• Constipation

• Abdominal pain
• Liver: increased levels of chemicals in the blood produced by the liver
• Increased skin pigmentation

• Itching of the skin
• Rash on the body where each lesion looks like a target

• Hair loss
• Hives
• Kidney failure

• Reduced kidney function
• Fever

• Pain
• Excess fluid in the body tissue that causes swelling

• Chest pain
• Inflammation and ulceration of the mucous membranes that line the digestive tract

Uncommon (may affect up to 1 in 100 people)

• Decrease in the number of red blood cells, white blood cells and platelets

• Ischemia or lack of blood flow
• Ischemia due to blockage of a cerebral artery
• Intracranial bleeding

• Angina (chest pain caused by reduced blood flow to the heart)
• Heart attack

• Narrowing or blockage of the coronary arteries
• Abnormal heart rhythm
• Poor blood distribution to the limbs

• Blockage in one of the pulmonary arteries in the lungs
• Inflammation and scarring of the lung mucosa with respiratory problems

• Loss of bright red blood through the anus
• Bleeding in the gastrointestinal tract
• Perforation of the intestine

• Inflammation of the esophagus
• Inflammation of the mucosa 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 mucous membrane surface of the esophagus caused by radiotherapy
• Radiation-induced lung inflammation

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

• Destruction of red blood cells
• Anaphylactic shock (severe allergic reaction)

• Inflammatory liver disease
• Redness of the skin

• Rash on the skin that develops in a previously irradiated area

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

• Infections 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 disorder that causes skin rashes and blisters on the legs, arms and abdomen
• Inflammation of the skin characterized by the presence of blisters that are filled with fluid
• Frailty of the skin, blisters and erosions and scarring of the skin

• Redness, pain and swelling mainly of the lower limbs
• Inflammation of the skin and the fat under the skin (pseudocellulitis)
• Inflammation of the skin (dermatitis)

• The skin becomes inflamed, itchy, red, cracked and rough
• Itchy patches

Frequency not known: frequency cannot be estimated from the available data

• A type of diabetes derived mainly from kidney disease

• Kidney disorder that involves the death of the epithelial cells that form the renal tubules

You may experience some of these symptoms and/or situations. You should tell your doctor as soon as you start experiencing any of these side effects.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Armisarte

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 label and carton after EXP. The expiry date is the last day of the month shown.

Store and transport refrigerated (2°C - 8°C).

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Solution for infusion: the chemical and physical stability of the pemetrexed infusion solution has been demonstrated for 24 hours at room temperature and for 7 days in refrigeration. From a microbiological point of view, the product should be used immediately. If not used immediately, the time and conditions of storage prior to use are the responsibility of the user and should not exceed 24 hours at 2°C - 8°C, unless the dilution has been made under controlled and validated sterile conditions.

Armisarte should not be used if particles are observed.

This medicine is for single use only. The unused solution should be disposed of in accordance with local regulations.

6. Container Content and Additional Information

Armisarte Composition

The active ingredient is pemetrexed. Each milliliter of concentrate contains 25 mg of pemetrexed (as pemetrexed disodium).

Each 4 ml vial of concentrate contains 100 mg of pemetrexed (in the form of pemetrexed disodium).

Each 20 ml vial of concentrate contains 500 mg of pemetrexed (in the form of pemetrexed disodium).

Each 34 ml vial of concentrate contains 850 mg of pemetrexed (in the form of pemetrexed disodium).

Each 40 ml vial of concentrate contains 1000 mg of pemetrexed (in the form of pemetrexed disodium).

The other components are trometamol (for pH adjustment), citric acid, methionine, and water for injectable preparations.

Product Appearance and Container Content

Armisarte concentrate for solution for infusion (sterile concentrate) is a clear, colorless solution, ranging from colorless to pale yellow or yellow-green.

Armisarte is presented in a colorless glass vial, with a rubber stopper and an aluminum cap with a polypropylene disc. The vials may or may not be covered with a protective sleeve.

Each Armisarte container contains one vial.

Package sizes:

Package with 1 vial of 4 ml (100 mg/4 ml).

Package with 1 vial of 20 ml (500 mg/20 ml).

Package with 1 vial of 34 ml (850 mg/34 ml).

Package with 1 vial of 40 ml (1000 mg/40 ml).

Only some package sizes may be marketed.

Marketing Authorization Holder

Actavis Group PTC ehf.

Reykjavíkurvegi 76-78

1. Hafnarfjörður Iceland

Manufacturer

PLIVA CROATIA Ltd.

10000 Zagreb

Prilaz baruna Filipovica 25

Croatia

Actavis Italy S.p.A.

Viale Pasteur 10

20014 Nerviano (Milan)

Italy

S.C. Sindan-Pharma S.R.L.

11 Ion Mihalache Blvd.

011171 Bucharest

Romania

For further information on this medicinal product, please contact the local representative of the marketing authorization holder.

Date of Last Revision of this Prospectus: June 2021

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended solely for healthcare professionals:

Instructions for use and handling and disposal

1. Use aseptic techniques during the dilution of pemetrexed for intravenous infusion administration.

1. Calculate the dose and the number of Armisarte vials needed.

1. Armisarte should only be diluted with a 5% glucose solution or 0.9% sodium chloride solution, without preservatives. The appropriate volume of pemetrexed concentrate should be diluted to 100 ml with a 5% glucose solution or 0.9% sodium chloride solution and should be administered as an intravenous infusion over 10 minutes.

1. The prepared pemetrexed infusion solution is compatible with polyvinyl chloride and polyolefin infusion systems and bags. Pemetrexed is incompatible with diluents containing calcium, including Ringer's lactate for injection and Ringer's injection.

Armisarte contains trometamol as an excipient. Trometamol is incompatible with cisplatin, as it degrades cisplatin. This medicinal product should not be mixed with other medicinal products, except those mentioned in section 6.6. After administration of Armisarte, the intravenous lines should be flushed.

1. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is observed, the medicinal product should not be administered.

1. Pemetrexed solutions are for single use. The medicinal product and any unused material should be disposed of in accordance with local regulations.

Precautions in preparation and administration

As with any potentially toxic antineoplastic agent, special care should be taken in the handling and preparation of pemetrexed infusion solutions. The use of gloves is recommended. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be flushed with copious amounts of water. Pemetrexed is not a vesicant drug. There is no specific antidote for pemetrexed extravasation. Some cases of pemetrexed extravasation have been reported, which were not considered serious by the investigator. Extravasation should be treated according to standard clinical practice for non-vesicant drugs.

Diluted solution

The chemical and physical stability of the pemetrexed infusion solution has been demonstrated for 24 hours at room temperature and for 7 days under refrigeration. From a microbiological point of view, 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 2°C-8°C, unless the dilution has been performed under controlled and validated aseptic conditions.

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