PEMETREXED ACCORD 1000 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Pemetrexed Accord 100 mg powder for concentrate for solution for infusion EFG

Pemetrexed Accord 500 mg powder for concentrate for solution for infusion EFG

Pemetrexed Accord 1000 mg powder for concentrate for solution for infusion EFG

pemetrexed

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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Pemetrexed Accord is a medicine used to treat cancer.

Pemetrexed Accord 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 Accord can also be given, along with cisplatin, as an initial treatment for patients with advanced stages of lung cancer.

Pemetrexed Accord 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 Accord 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 you use Pemetrexed Accord

Do not usePemetrexed Accord :

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

Warnings and precautions

Tell your doctor, pharmacist, or hospital nurse before you are given Pemetrexed Accord.

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

Before each infusion, you will have 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 Pemetrexed Accord. 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 Pemetrexed Accord.

If you have been vaccinated recently, please consult your doctor, as this may cause some negative effect with Pemetrexed Accord.

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 remove the fluid before administering Pemetrexed Accord.

Children and adolescents

No relevant data are available on the use of Pemetrexed Accord in the pediatric population.

Use of Pemetrexed Accord with other medicines

Tell your doctor if you are taking medicines for pain or inflammation (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (NSAIDs), including those purchased without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your Pemetrexed Accord 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 unsure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

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

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. During pregnancy, the use of Pemetrexed Accord should be avoided. Your doctor will inform you of the possible risks of taking Pemetrexed Accord during pregnancy. Women must use effective contraceptive methods during treatment with Pemetrexed Accord.

Breast-feeding

If you are breast-feeding, inform your doctor.

Breast-feeding should be discontinued during treatment with Pemetrexed Accord.

Fertility

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

Driving and using machines

Pemetrexed Accord may cause fatigue. Be careful when driving a vehicle or using machines.

Pemetrexed Accord contains sodium

Pemetrexed Accord 100 mg contains less than 1 mmol of sodium (23 mg) per vial, i.e., essentially "sodium-free".

Pemetrexed Accord 500 mg contains approximately 54 mg of sodium per vial, which should be taken into account in patients with low-sodium diets.

Pemetrexed Accord 1000 mg contains approximately 108 mg of sodium per vial, which should be taken into account in patients with low-sodium diets.

3. How to use Pemetrexed Accord

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose of Pemetrexed Accord 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 general condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Accord powder with a sodium chloride solution for injection of 9 mg/ml (0.9%) before it is given to you.

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

When using Pemetrexed Accord 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 Accord infusion has finished. The cisplatin infusion lasts approximately 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 Pemetrexed Accord. 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 that contains folic acid (350 to 1,000 micrograms) that you must take once a day while taking Pemetrexed Accord. You must take at least 5 doses during the 7 days before the first dose of Pemetrexed Accord. You must continue taking folic acid during 21 days after the last dose of Pemetrexed Accord. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before administration of Pemetrexed Accord and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Accord). 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 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 (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 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 experience 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 very frequent).
• If you experience sudden difficulty breathing, severe chest pain, or coughing up blood (uncommon) (may indicate a blood clot in the lungs).

Side effects with Pemetrexed Accord may include:

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

Low white blood cell count

Low hemoglobin levels (anemia)

Low platelet count

Diarrhea

Vomiting

Pain, redness, swelling, or sores in the mouth

Nausea

Lack of appetite

Asthenia (fatigue)

Rash

Hair loss

Constipation

Numbness

Kidney: changes in blood tests

Common (may affect up to 1 in 10 people)

Allergic reaction: rash / burning sensation or itching

Infection including sepsis

Fever

Dehydration

Kidney failure

Skin irritation and itching

Chest pain

Muscle weakness

Conjunctivitis (eye inflammation)

Upset stomach

Abdominal pain

Changes in taste

Liver: changes in blood tests

Tearful eyes

Increased skin pigmentation

Uncommon (may affect up to 1 in 100 people)

Acute kidney failure

Fast heart rate

Esophageal mucositis (inflammation of the esophagus) after combination of Pemetrexed Accord and radiotherapy

Colitis (inflammation of the colon, which may be accompanied by intestinal or rectal bleeding)

Interstitial pneumonitis (scarring of the lung air sacs)

Edema (excess fluid in the body tissues causing swelling)

Some patients have experienced a heart attack, embolism, or "mini-stroke" while receiving Pemetrexed Accord, usually in combination with other anticancer treatment.

Pancytopenia: combination of low white blood cell count, low red blood cell count, and low platelet count.

Radiation pneumonitis (scarring of the lung air sacs associated with radiotherapy) may occur in patients who are being treated with radiation before, during, or after treatment with Pemetrexed Accord.

Pain in the limbs, low body temperature, and changes in skin color have been reported.

Blood clots in the lungs (pulmonary embolism)

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

Delayed skin toxicity (skin rash similar to severe sunburn) that can appear on skin that has been previously exposed to radiation, from days to years after radiation.

Bullous disorders (diseases with blistering of the skin) including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Immune-mediated hemolytic anemia (destruction of red blood cells by antibodies)

Hepatitis (inflammation of the liver)

Anaphylactic shock (severe allergic reaction)

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

Swelling of the lower limbs with pain and redness.

Increased urine output.

Thirst and increased water intake.

Hypernatremia: high sodium levels in the blood.

Skin inflammation, mainly of the lower limbs with swelling, pain, and redness.

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, consult your doctor.

Reporting of side effects

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

5. Storage of Pemetrexed Accord

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.

This medicine does not require any special storage conditions.

Reconstituted and infusion solution: the medicine should be used immediately. When prepared as indicated, the chemical and physical stability in use of the reconstituted and infusion solution is 24 hours in refrigeration.

Do not use this medicine if you notice any visible signs of deterioration.

This medicine is for single use only. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Pemetrexed Accord

The active ingredient is pemetrexed.

Pemetrexed Accord 100 mg: Each vial contains 100 mg of pemetrexed (as pemetrexed disodium hemipentahydrate)

Pemetrexed Accord 500 mg: Each vial contains 500 mg of pemetrexed (as pemetrexed disodium hemipentahydrate)

Pemetrexed Accord 1000 mg: Each vial contains 1000 mg of pemetrexed (as pemetrexed disodium hemipentahydrate)

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

The other components are mannitol, hydrochloric acid, and sodium hydroxide (see section 2).

Appearance of Pemetrexed Accord and Container Content

Pemetrexed Accord is a powder for concentrate for solution for infusion in a glass vial. It is a lyophilized powder of white to pale yellow or yellowish-green color. Each pack of Pemetrexed Accord contains one vial.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Limited

Sage House

319, Pinner Road

North Harrow

Middlesex HA1 4HF

United Kingdom

Wessling Hungary Kft.

Fòti ùt 56., Budapest, 1047,

Hungary

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice, Poland

Date of Last Revision of this Leaflet

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 only for healthcare professionals

Instructions for Use and Handling and Disposal

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

1. Calculate the dose and the number of Pemetrexed Accord vials needed. Each vial contains an excess of pemetrexed to facilitate the administration of the required nominal amount.

1. Pemetrexed Accord 100 mg

Reconstitute each 100 mg vial with 4.2 ml of a 0.9% sodium chloride injection solution (9 mg/ml), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed Accord 500 mg:

Reconstitute each 500 mg vial with 20 ml of a 0.9% sodium chloride injection solution (9 mg/ml), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed

Pemetrexed Accord 1000 mg:

Reconstitute each 1000 mg vial with 40 ml of a 0.9% sodium chloride injection solution (9 mg/ml), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Shake the vial carefully until the powder is completely dissolved. The resulting solution is transparent with a color range that may vary from colorless to yellow or yellowish-green without affecting the product quality. The pH of the reconstituted solution is between 6.6 and 7.8. A subsequent dilution is required.

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

1. The pemetrexed infusion solution prepared according to the instructions described above 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.

1. Parenteral medicinal products should be inspected visually prior to administration for particulate matter or discoloration. If particles are 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 according to local requirements.

Storage

The chemical and physical in-use stability of the reconstituted and infusion solutions of pemetrexed has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C, unless the reconstitution/dilution has taken place in controlled and validated aseptic conditions.

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. 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 for non-vesicant drugs.