Prospecto: Information for the User

Armisarte 25 mg/ml Concentrate for Solution for Infusion

pemetrexed

Read this prospect carefully before starting to receive this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor, nurse or pharmacist, even if they are not listed in this prospect. See section 4.

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

1. Contents of the package and additional information

Armisarte is a medication used for the treatment of cancer that contains the active ingredient pemetrexed. Pemetrexed belongs to a group of medications known as «folic acid analogs» and interrupts the processes that are essential for cell division.

Armisarte can be administered along with cisplatino, another anticancer medication, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lung mucosa, in patients who have not received prior chemotherapy.

Armisarte can also be administered, along with cisplatino, for the initial treatment of patients in advanced stages of lung cancer.

Armisarte may be prescribed 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 administered for the treatment of patients in advanced stages of lung cancer whose disease has progressed, who have already received initial chemotherapy treatment.

Do not use Armisarte

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

• if you are breastfeeding, you must stop breastfeeding during treatment with Armisarte.
• if you have recently received the yellow fever vaccine or are about to receive it.

Warnings and precautions

Consult your doctor or hospital pharmacist before Armisarte is administered to you.

If you have or have had kidney problems, tell your doctor or hospital pharmacist as it may be possible that you cannot receive Armisarte.

Before each infusion, you will need to provide blood samples to evaluate if your renal and hepatic function is sufficient and to evaluate if you have enough blood cells to receive Armisarte. Your doctor may decide to change your dose or delay treatment depending on your overall condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will ensure that you are properly hydrated and receive the appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are about to receive radiation therapy, please consult with your doctor, as there may be an early or late reaction between the radiation and Armisarte.

If you have recently been vaccinated, please consult with your doctor, as it may be possible that this could cause some negative effect with Armisarte.

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

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

Children and adolescents

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

Use of Armisarte with other medications

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication, including pain or anti-inflammatory medications (such as nonsteroidal anti-inflammatory drugs or NSAIDs), including those obtained 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 your renal function, your doctor will advise you which medications you can use and when. If you are unsure, consult your doctor or pharmacist to see if any medication you are taking is an NSAID.

Like other chemotherapy medications, it is not recommended to use Armisarte with attenuated vaccines. Whenever possible, inactivated vaccines should be used.

Pregnancy

If you are pregnant, think you may be pregnant, or intend to become pregnant,informyour doctor. During pregnancy, the use of Armisarte should be avoided. Your doctor will inform you of the possible risks of taking Armisarte during pregnancy. Women should use effective contraceptive methods during treatment with Armisarte.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with Armisarte, breastfeeding should be interrupted.

Fertility

Men are advised not to father a child during and up to 6 months after treatment with Armisarte, and therefore, should 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, please consult your doctor or pharmacist. You may wish to request information on sperm preservation before starting your treatment.

Driving and operating machinery

Armisarte may make you feel tired. Be careful when driving a vehicle or operating machinery.

Armisarte 25 mg/ml concentrated solution for infusion will be administered by a healthcare professional. The dose of Armisarte is 500 milligrams per square meter of the surface area of your body. 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 overall condition. The hospital pharmacist, nurse, or doctor will have mixed Armisarte with a 5% glucose solution for injection or in a 0.9% sodium chloride solution for injection before it is administered to you.sodium chloride0.9%for injection

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

When using Armisarte in combination with cisplatino:

Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatino is also administered through an infusion in one of your veins and is given approximately 30 minutes after you have finished the Armisarte infusion. The cisplatino infusion lasts approximately two hours.

You should normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe some steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will have to take the day before, on the same day, and the day after treatment with Armisarte. Your doctor will give you this medication to reduce the frequency and severity of skin reactions 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 should take once a day while taking Armisarte. You should take at least five doses during the seven days before the first dose of Armisarte. You should continue taking folic acid for 21 days after the last dose of Armisarte. You will also receive an injection of vitamin B12(1,000 micrograms) the week before administration of Armisarte and approximately every 9 weeks (corresponding to 3 cycles of treatment with Armisarte). Vitamin B12and folic acid are given to reduce possible toxic effects of cancer treatment.

During treatment, close monitoring of your disease will be performed, which involves periodic blood tests to check, among other things, liver and kidney function. Depending on the results obtained in these tests, it may be necessary to modify your dose or postpone your treatment.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• Fever or infection (frequent): if you have a temperature of 38°C or higher, sweating, or other signs of infection (since you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and cause death.

• If you start to feel chest pain (frequent) or your heart rate is faster (rare).
• If you have pain, redness, swelling, or sores in your mouth (very frequent).
• Allergic reaction: if you develop hives (very frequent), burning sensation or itching (frequent), or fever (frequent). In rare cases, skin reactions can be severe and may cause death. Contact your doctor if you present severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you lack breath or are pale (because you have fewer hemoglobin than normal, which is very frequent).
• If you experience bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruises (because you have fewer platelets than normal, which is very frequent).

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

Other side effects that Armisarte may include:

Very frequent (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 hemoglobin levels
• Pain, redness, swelling, or sores in the mouth
• Loss of appetite

• Vomiting
• Diarrhea

• Nausea
• Skin rash
• Scaly skin

• Abnormal blood test results showing reduced kidney function
• Asthenia (fatigue)

Frequent (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
• Fluid loss
• Alterations in taste

• Damage to motor nerves that can cause muscle weakness and atrophy (emaciation mainly in arms and legs)

• Damage to sensory nerves that can cause numbness, burning sensation, and unstable gait
• Dizziness

• Conjunctival inflammation or swelling (membrane covering the eyelids and covering the white part of the eye)
• Dry eye
• Watery eyes
• Dryness of the conjunctiva (inner membrane of the eyelids and covering the white part of the eye) and cornea (transparent layer in front of the iris and pupil)
• Swelling of the eyelids

• Ocular disorder with dryness, tearing, irritation, and/or pain
• Heart failure (condition affecting the heart's pumping ability)
• Irregular heart rhythm

• Indigestion
• Constipation

• Abdominal pain
• Liver: increased substances in the blood produced by the liver
• Increased skin pigmentation

• Itching skin
• Rash on the body where each lesion resembles a target

• Hair loss
• Urticaria
• Renal failure

• Reduced kidney function
• Fever

• Pain
• Excess fluid in the body tissue causing swelling

• Chest pain
• Inflammation and ulceration of the mucous membranes lining the digestive tract internally

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

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

• Inflammatory liver disease
• Skin redness

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

Very rare (may affect 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 can be fatal)

• Toxic epidermal necrolysis (a type of severe skin reaction that can be fatal)
• Autoimmune disorder causing skin rashes and blisters on the legs, arms, and abdomen
• Inflammation of the skin characterized by the presence of blisters filled with fluid
• Skin fragility, blisters, and erosions, and skin scars

• Redness, pain, and swelling mainly in the lower limbs
• Inflammation of the skin and subcutaneous fat (pseudocelulitis)
• Inflammation of the skin (dermatitis)

• The skin becomes inflamed, itches, reddens, cracks, and becomes rough
• Intensely itchy spots

Frequency unknown: the frequency cannot be estimated from available data

• A type of diabetes mainly derived from kidney disease

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

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label and on the box after CAD. The expiration date is the last day of the month indicated.

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

Do not freeze.

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

Infusion solution: chemical and physical stability has been demonstrated during the use of the pemetrexed infusion solution for 24 hours at room temperature and 7 days refrigerated. From a microbiological standpoint, the product must be used immediately. If not used immediately, the time and storage 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 sterile conditions.

Unless the dilution has been performed under controlled and validated sterile conditions.

Armisarte should not be used if particles are observed.

This medication is for single use only. Unused solution should be disposed of in accordance with local regulations.

Composition of Armisarte

The active principle is pemetrexed. Each milliliter of concentrate contains 25 mg of pemetrexed (as pemetrexed diacid).

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

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

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

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

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

Appearance of the product and contents of the package

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

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

Each package of Armisarte contains one vial.

Packaging 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 packaging sizes may be commercially available.

Marketing authorization holder

Actavis Group PTC ehf.

Reykjavíkurvegi 76-78

1. Hafnarfjörður, Iceland

Responsible for manufacturing

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 more information about this medication, please contact the local representative of the marketing authorization holder.

Last review date of this leaflet: June 2021

Other sources of information

More detailed information on this medicine is available on the website of the European Medicines Agency

http://www.ema.europa.euand on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)

http://www.aemps.gob.es/.

-------------------------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Instructions for use and handling and disposal

1. Use aseptic techniques when diluting pemetrexed for intravenous infusion.

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

1. Armisarte should only be diluted with a 5% glucose solution or a 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 a 0.9% sodium chloride solution, and should be administered as an intravenous infusion over 10 minutes.

1. The pemetrexed infusion solution prepared according to the above instructions is compatible with PVC and polyolefin infusion systems and bags. Pemetrexed is incompatible with calcium-containing diluents, including lactated Ringer's injection and Ringer's injection.

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

1. Parenteral medicines should be visually inspected before administration to ensure that there are no particles or color changes. If particles are observed, the medicine should not be administered.

1. The pemetrexed solutions are for single use only. The medicine and unused materials should be disposed of in accordance with local regulations.

Precautions in preparation and administration

As with any other potentially toxic antineoplastic agent, special care should be taken in the handling and preparation of pemetrexed solutions for intravenous infusion. The use of gloves is recommended for handling. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and abundantly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be washed with plenty of 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 serious by the investigator. Extravasation should be treated according to standard clinical practice with non-vesicant medicines.

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 time and storage conditions prior to use are the responsibility of the user and should not exceed 24 hours at 2-8°C, unless the dilution has been performed under controlled and validated sterile conditions.

43