PEMETREXED AUROVIT 25 mg/mL concentrate for infusion solution

Introduction

Package Leaflet: Information for the User

Pemetrexed Aurovit 25 mg/ml concentrate for solution for infusion

Read all of this leaflet carefully before you start 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 or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Pemetrexed Aurovit is a medicine used to treat cancer.

Pemetrexed 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.

Pemetrexed can also be given with cisplatin for the initial treatment of patients with advanced lung cancer.

Pemetrexed 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.

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

2. What you need to know before you use Pemetrexed Aurovit

Do not usePemetrexed Aurovit

• if you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding, you must stop breast-feeding during treatment with pemetrexed.
• if you have recently been given the yellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before starting treatment with Pemetrexed Aurovit.

• if you have had or have kidney problems, as you may not be able to receive pemetrexed.

Before each infusion, you will need to give blood samples to check if your kidney and liver function are sufficient and to check if you have enough blood cells to receive pemetrexed. 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 ensure that 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, as an early or late reaction may occur between radiation and pemetrexed.
• if you have been vaccinated recently, as this may cause a negative effect with pemetrexed.
• if you have a heart condition or a history of heart disease.
• if you have fluid accumulated around the lung, your doctor may decide to remove the fluid before administering pemetrexed.

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.

Other medicines andPemetrexed Aurovit

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription.

Tell your doctor or pharmacist if you are taking any medicine for pain or inflammation(swelling), such as medicines called “non-steroidal anti-inflammatory drugs” (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 pemetrexed infusion and/or the status of your kidney function, your doctor will advise you which medicines you can use and when you can take them. If you are not sure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

Tell your doctor if you are taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) used to treat stomach acid and acid reflux.

Pregnancy, breast-feeding and fertility

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor. During pregnancy, the use of pemetrexed should be avoided. Your doctor will inform you of the possible risks of using pemetrexed during pregnancy. Women must use effective contraceptive methods during treatment with pemetrexed and for 6 months after receiving the last dose.

Breast-feeding

If you are breast-feeding, tell your doctor.

Breast-feeding must be stopped during treatment with pemetrexed.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with pemetrexed and must use effective contraceptive methods during and up to 3 months after treatment with pemetrexed. If you wish to have a child during treatment or in the 3 months following treatment, ask your doctor or pharmacist for advice. Pemetrexed may affect your ability to have children. Talk to your doctor about sperm preservation before starting your treatment.

Driving and using machines

Pemetrexed may make you feel tired. Be careful when driving a car or using machines.

Pemetrexed Aurovit contains propylene glycol

This medicine contains 140 mg of propylene glycol in each 4 ml vial, equivalent to 35 mg/ml.

This medicine contains 700 mg of propylene glycol in each 20 ml vial, equivalent to 35 mg/ml.

This medicine contains 1,400 mg of propylene glycol in each 40 ml vial, equivalent to 35 mg/ml.

3. How to use Pemetrexed Aurovit

The dose of pemetrexed 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 diluted pemetrexed with a sodium chloride 9 mg/ml (0.9%) or glucose 5% injection solution before administration.

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

When using Pemetrexed Aurovit 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 approximately 30 minutes after the pemetrexed infusion has finished. The cisplatin infusion lasts approximately 2 hours.

Normally, you should 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 will need to take the day before, the day of, and the day after treatment with pemetrexed. Your doctor gives you this medicine 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 using pemetrexed. You should take at least 5 doses during the 7 days before the first dose of pemetrexed. You should continue taking folic acid during 21 days after the last dose of pemetrexed. Additionally, you will receive a vitamin B12 (1,000 micrograms) injection in the week before pemetrexed administration and then approximately every 9 weeks (corresponding to 3 cycles of treatment with pemetrexed). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

If you have any further questions on the use of this medicine, 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 (frequent or very frequent, respectively): 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 frequent). Infections (sepsis) can be serious and life-threatening.
• if you start to feel chest pain (frequent) or your heart rate is faster (uncommon).
• if you have pain, redness, swelling, or sores in the mouth (very frequent).
• allergic reaction: if you develop a rash (very frequent), burning sensation, or itching (frequent), or fever (frequent). In rare cases, skin reactions can be serious and life-threatening. Contact your doctor if you have a severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• if you feel tired or dizzy, if you are short of breath or are pale (due to having fewer red blood cells than normal, which is very frequent).
• if you experience bleeding from the 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 frequent).
• 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 veins of the lungs).

Side effects with pemetrexed 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 • skin rash • scaly skin • changes in blood tests showing reduced kidney function • fatigue (tiredness).

Common(may affect up to 1 in 10 people)

blood infection • fever with low neutrophil count • low platelet count • allergic reaction • loss of body fluids • changes in taste • nerve damage that can cause muscle weakness and wasting (debilitating) mainly in arms and legs • nerve damage that can cause loss of sensation, burning (pain), and unsteady walking • dizziness • conjunctivitis (inflammation or swelling of the membrane that covers the white part of the eye) • dry eyes • tearing • dryness of the conjunctiva (membrane inside the eyelids and covering the white part of the eye) and cornea (clear 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 • skin rash that 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)

reduction in the number of red blood cells, white blood cells, and platelets • ischemia or lack of blood flow • cerebral artery occlusion • intracranial bleeding • angina (chest pain caused by reduced blood flow to the heart) • heart attack • narrowing or blockage of the coronary arteries • increased heart rate • 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 • bright red blood loss through the anus • bleeding in the gastrointestinal tract • intestinal perforation • esophageal mucosa inflammation • 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)

red blood cell destruction • anaphylactic shock (severe allergic reaction) • liver inflammatory disease • skin redness • skin rash that develops 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 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 • skin inflammation characterized by the presence of blisters filled with fluid • skin fragility, blisters, and erosions and scarring • redness, pain, and swelling mainly of the lower limbs • skin and subcutaneous tissue inflammation (pseudocellulitis) • skin inflammation (dermatitis) • skin becomes inflamed, itchy, red, cracked, and rough • itchy spots.

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

a type of diabetes derived mainly from kidney disease • kidney disorder involving the death of the epithelial cells that form the renal tubules.

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

If you are concerned about any side effect, talk to your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pemetrexed Aurovit

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 refers to the last day of the month shown.

This medicine does not require any special storage conditions.

Do not freeze.

Diluted solution for infusion: The medicine should be used immediately. When prepared as indicated, the chemical and physical stability of pemetrexed during use has been demonstrated for 24 hours at refrigerated temperature. Store protected from light.

This medicine is for single use; the unused solution should be discarded in accordance with local regulations.

6. Container contents and additional information

Composition of Pemetrexed Aurovit

The active ingredient is pemetrexed.

A 4 ml vial of concentrate contains 100 mg of pemetrexed (as pemetrexed diarginine).

A 20 ml vial of concentrate contains 500 mg of pemetrexed (as pemetrexed diarginine).

A 40 ml vial of concentrate contains 1,000 mg of pemetrexed (as pemetrexed diarginine).

The solution contains 25 mg/ml of pemetrexed. Before administration, it is required that the healthcare professional perform further dilution.

The other components are L-arginine, L-cysteine, propylene glycol, citric acid, and water for injectable preparations.

Appearance and container size of the product

Pemetrexed Aurovit is a clear, colorless to slightly yellowish, brown, yellowish-brown or greenish-yellow solution. Pemetrexed Aurovit is presented in a glass vial.

Each container contains:

1 vial of 4 ml (100 mg/4 ml)

1 vial of 20 ml (500 mg/20 ml)

1 vial of 40 ml (1,000 mg/40 ml)

The vials are closed with a rubber stopper (bromobutyl), a closure cap, and a flip-top cap.

Marketing authorization holder and manufacturer

Marketing authorization holder

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Manufacturer:

Synthon Hispania, S.L.

C/ Castelló 1, Pol. Las Salinas

08830 Sant Boi de Llobregat (Barcelona)

Spain

or

Synthon BV

Microweg 22,

6545 CM Nijmegen

Netherlands

or

Synthon s.r.o.

Brnenská 32/cp. 597,

678 01 Blansko

Czech Republic

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Germany: Pemetrexed Ribosepharm 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Spain: Pemetrexed Aurovit 25 mg/ml concentrate for solution for infusion

Finland: Pemetrexed Avansor 25 mg/ml Infuusiokonsentraatti, liuosta varten

France: Pemetrexed Stragen® 25 mg/ml, solution à diluer pour perfusion

Netherlands: Pemetrexed Synthon 25 mg/ml, concentraat voor oplossing voor infusie

Poland: Pemetrexed Adamed

Romania: Pemetrexed Alvogen 25 mg/ml concentrat pentru solutie perfuzabila

Date of the last revision of this leaflet:January 2025

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

This information is intended only for healthcare professionals:

Instructions for use, handling, and disposal

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

1. Calculate the dose and volume of Pemetrexed Aurovit needed. Each vial contains an excess of pemetrexed to facilitate the administration of the required nominal amount. Each vial contains a solution that contains 25 mg/ml of pemetrexed.

1. The appropriate volume of pemetrexed concentrate should be diluted to 100 ml with a 9 mg/ml (0.9%) sodium chloride injectable solution or a 5% glucose solution, without preservatives, and administered as an intravenous infusion over 10 minutes.

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

Pemetrexed Aurovit contains L-Arginine as an excipient. L-Arginine is incompatible with cisplatin, as it degrades cisplatin. This medicinal product should not be mixed with others. After administration of Pemetrexed Aurovit, the intravenous lines should be flushed.

1. Medicines for parenteral administration should be visually inspected before administration to rule out the presence of particles or color alteration. If particles are observed, the medicinal product should not be administered.

1. Pemetrexed solutions are for single use. The medicinal product and unused material should be discarded according to local regulations for cytotoxic agents.

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 infusion solutions. The use of gloves is recommended for handling. 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 rinsed with plenty 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 with other non-vesicant drugs.