Armisarte 25 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

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 questions, ask your doctor or pharmacist.

• If you experience any side effects, talk to your doctor, nurse or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Armisarte is and what it is used for

2. What you need to know before receiving Armisarte

3. How to use Armisarte

4. Possible side effects

5. How to store Armisarte

6. Contents of the pack and other information

1. What Armisarte is and what it is used for

Armisarte is a cancer medicine that contains the active substance pemetrexed. Pemetrexed belongs to a group of medicines known as "folic acid analogues" and interferes with processes essential for cell division.

Armisarte may be given together with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a form of cancer affecting the lining of the lung, in patients who have not previously received chemotherapy.

Armisarte may also be given together with cisplatin as initial treatment for patients with advanced-stage lung cancer.

Armisarte may be prescribed to you if you have advanced-stage lung cancer and your disease has responded to treatment or has remained unchanged after initial chemotherapy.

Armisarte may also be given for the treatment of patients with advanced-stage lung cancer whose disease has progressed, and who have already received prior initial chemotherapy treatment.

2. What you need to know before using Armisarte

Do not use Armisarte

• 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 interrupt breastfeeding during treatment with Armisarte.

• if you have recently received or are scheduled to receive the yellow fever vaccine.

Warnings and precautions

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

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

Before each infusion, you will need to provide blood samples to assess whether your kidney and liver function are adequate and to evaluate whether you have sufficient blood cells to receive Armisarte. Your doctor may decide to adjust 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 ensure that you are properly hydrated and will administer appropriate treatment before and after cisplatin to prevent vomiting.

If you have received or are scheduled to receive radiotherapy, please consult your doctor, as there may be an early or delayed interaction between radiation and Armisarte.

If you have been recently vaccinated, please consult your doctor, as vaccination may potentially cause adverse effects when combined with Armisarte.

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

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

Children and adolescents

This medicine should not be used in children or adolescents, as there is no experience with this medicine in individuals under 18 years of age.

Use of Armisarte with other medicines

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

As with other chemotherapeutic agents, the use of Armisarte together with live attenuated vaccines is not recommended. Inactivated vaccines should be used whenever possible.

Pregnancy

If you are pregnant, think you might be pregnant, or plan to become pregnant, inform your doctor. Armisarte should be avoided during pregnancy. Your doctor will inform you of the potential risks of taking Armisarte during pregnancy. Women should use effective contraceptive methods during treatment with Armisarte.

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding must be discontinued during treatment with Armisarte.

Fertility

Male patients are advised not to father a child during and for 6 months after treatment with Armisarte, and therefore should use effective contraception during and for 6 months after treatment with Armisarte. If you wish to father a child during treatment or within 6 months after treatment, seek advice from your doctor or pharmacist. You may wish to request information about sperm preservation before starting treatment.

Driving and use of machines

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

3. How to use Armisarte

Armisarte 25 mg/ml concentrate for solution for infusion will always be administered by a healthcare professional. The dose of Armisarte is 500 milligrams per square metre of your body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this measurement to determine 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 5% glucose solution for injection or with 0.9% sodium chloride solution for injection before administration.

You will always receive Armisarte as an intravenous infusion (drip) into 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 require based on your height and weight. Cisplatin is also administered by infusion into one of your veins and is given approximately 30 minutes after the Armisarte infusion has finished. The cisplatin infusion lasts approximately two hours.

You will normally receive your infusion once every three weeks.

Additional medication:

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 your Armisarte treatment. Your doctor prescribes 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 containing folic acid (350 to 1,000 micrograms), to be taken once daily during your treatment with Armisarte. You should take at least five doses during the seven days prior to your first dose of Armisarte. You should continue taking folic acid for 21 days after your last dose of Armisarte. In addition, you will receive a vitamin B12 injection (1,000 micrograms) during the week before your first Armisarte dose and then approximately every 9 weeks (corresponding to 3 cycles of Armisarte treatment). Vitamin B12 and folic acid are given to reduce the potential toxic effects of cancer treatment.

During treatment, your condition will be closely monitored, including periodic blood tests to check, among other things, liver and kidney function. Depending on the results of these tests, your dose may be modified or your treatment postponed.

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

4. Possible adverse effects

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

You should 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 (as you may have fewer white blood cells than normal, which is very common). Infections (sepsis) can be severe and may cause death.

• If you begin to feel chest pain (frequent) or your heartbeat becomes 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 severe and may cause death. Contact your doctor if you experience severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).

• If you feel tired or dizzy, are short of breath, or appear pale (due to having lower than normal hemoglobin levels, which is very common).

• If you experience bleeding from gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (due to having fewer platelets than normal, which is very common).

• If you suddenly experience difficulty breathing, severe chest pain, or coughing up blood in sputum (uncommon) (this may indicate a blood clot in the veins of the lungs).

Other adverse effects with Armisarte 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 hemoglobin levels

• Pain, redness, swelling, or sores in the mouth

• Loss of appetite

• Vomiting

• Diarrhea

• Nausea

• Skin rash

• Scaly skin

• Abnormal blood tests showing reduced kidney function

• Asthenia (weakness, fatigue)

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

• Changes in taste sensation

• Damage to motor nerves, which may cause muscle weakness and atrophy (wasting, mainly in arms and legs)

• Damage to sensory nerves, which may cause loss of sensation, burning pain (burning discomfort), 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 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

• Eye disorder with dryness, tearing, irritation, and/or pain

• Heart failure (a condition affecting the heart muscle's ability to pump)

• Irregular heartbeat

• Indigestion

• Constipation

• Abdominal pain

• Liver: increased liver-produced chemicals in the blood

• Increased skin pigmentation

• Itching of the skin

• Rash on the body where each lesion resembles a target (bull's-eye rash)

• Hair loss

• Hives

• Kidney failure

• 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 internally

Uncommon (may affect up to 1 in 100 people)

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

• Ischemia or inadequate blood supply

• Ischemia due to blockage of a cerebral artery

• Intracranial bleeding

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

• Infarction

• Narrowing or blockage of the coronary arteries

• Abnormal heart rhythm

• Poor blood distribution to the extremities

• Blockage in one of the pulmonary arteries in the lungs

• Inflammation and scarring of the lung mucosa causing breathing problems

• Bright red blood loss from the anus

• Bleeding in the gastrointestinal tract

• Intestinal perforation

• Inflammation of the esophageal mucosa

• Inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only in combination with cisplatin)

• Inflammation, edema, erythema, and erosion of the esophageal mucosal surface caused by radiotherapy

• Inflammation of the lung 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 disease

• Skin redness

• Skin rash developing in a previously irradiated area

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 legs, arms, and abdomen

• Skin inflammation characterized by the presence of fluid-filled blisters

• Skin fragility, blistering, erosions, and scarring of the skin

• Redness, pain, and swelling mainly in the lower limbs

• Inflammation of the skin and underlying fat (pseudocellulitis)

• Skin inflammation (dermatitis)

• Skin becomes inflamed, itchy, red, cracked, and rough

• Intensely itchy spots

Frequency not known: frequency cannot be estimated from available data

• A type of diabetes mainly resulting from kidney disease

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

You may experience one or more of these symptoms and/or conditions. You should inform your doctor as soon as you begin to experience any of these adverse effects.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the label and on the carton after EXP. The expiry date is the last day of the month indicated.

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

Do not freeze.

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

Concentrate for solution for infusion: 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 standpoint, the product should be used immediately. If not used immediately, the duration 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 was carried out under controlled and validated aseptic conditions.

Armisarte must not be used if particulate matter is observed.

This medicine is for single use only. Any unused solution should be discarded according to local regulations.

6. Contents of the pack and other information

Composition of Armisarte

The active substance is pemetrexed. Each millilitre of concentrate contains 25 mg of pemetrexed (as pemetrexed diacid).

Each 4 ml vial of concentrate contains 100 mg of pemetrexed (as pemetrexed diacid).

Each 20 ml vial of concentrate contains 500 mg of pemetrexed (as pemetrexed diacid).

Each 34 ml vial of concentrate contains 850 mg of pemetrexed (as pemetrexed diacid).

Each 40 ml vial of concentrate contains 1000 mg of pemetrexed (as pemetrexed diacid).

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

Appearance of the product and contents of the pack

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

Armisarte is supplied in a colourless glass vial, with a rubber stopper and aluminium cap with a polypropylene disc. The vials may or may not be covered with a protective sheath.

Each pack of Armisarte contains one vial.

Pack sizes:

Pack containing 1 vial of 4 ml (100 mg/4 ml).

Pack containing 1 vial of 20 ml (500 mg/20 ml).

Pack containing 1 vial of 34 ml (850 mg/34 ml).

Pack containing 1 vial of 40 ml (1000 mg/40 ml).

Only some pack sizes may be marketed.

Marketing Authorisation 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

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorisation Holder.

Date of the most recent review of this leaflet: June 2021

Other sources of information

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

This information is intended for healthcare professionals only:

Instructions for use, handling and disposal

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

2. Calculate the required dose and number of Armisarte vials needed.

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

4. The prepared pemetrexed infusion solution, as described above, is compatible with polyvinyl chloride and polyolefin infusion bags and systems. Pemetrexed is incompatible with diluents containing calcium, including injection lactated Ringer's solution and injection Ringer's solution.

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

2. Pemetrexed solutions are for single use only. Unused medicinal product and waste material must be disposed of in accordance with local regulations.

Precautions for preparation and administration

As with any other potentially toxic antineoplastic agent, special care should be taken in handling and preparing pemetrexed infusion solutions. The use of gloves is recommended. If pemetrexed solutions come 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, none of which were considered serious by the investigator. Extravasation should be managed according to standard clinical practice for non-vesicant drugs.

Diluted solution

The chemical and physical in-use stability of the pemetrexed infusion solution has been demonstrated for 24 hours at room temperature and for 7 days under refrigeration (2°C–8°C). From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the user's responsibility and must not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

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