PEMETREXED ACCORD 25 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Pemetrexed Accord 25 mg/ml concentrate for solution for infusion

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 experience 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 Pemetrexed Accord is and what it is 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 Pemetrexed Accord is and what it is 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 prior chemotherapy.

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, and who have already received other initial chemotherapy treatment.

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

Do not use Pemetrexed Accord:

• if you are allergic (hypersensitive) to pemetrexed or any of the other ingredients of Pemetrexed Accord (listed in section 6).
• if you are breastfeeding, you must discontinue breastfeeding during treatment with Pemetrexed Accord.
• if you have recently received or are going to receive the yellow fever vaccine.

Warnings and precautions

Talk to 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 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 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 a reaction may occur between the radiation and Pemetrexed Accord.

If you have recently been vaccinated, please consult your doctor, as this may cause a 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 drain the fluid before administering Pemetrexed Accord.

Children and adolescents

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

Using 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 bought 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 bought 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 and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with Pemetrexed Accord, breastfeeding must be discontinued.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with Pemetrexed Accord, and must use effective contraceptive methods during and up to 3 months after treatment with Pemetrexed Accord. If you wish to father a child during treatment or in the 3 months following treatment, consult your doctor or pharmacist. Pemetrexed Accord may affect your ability to father a child. Talk to your doctor about 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

The maximum daily dose of this medicine contains 304 mg of sodium (a component of table salt). This is equivalent to 15.2% of the maximum recommended daily intake of sodium for an adult.

Consult your pharmacist or doctor if you need to take Pemetrexed Accord for a prolonged period, especially if you have been advised to follow a low-salt diet.

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 your general condition.

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 that 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 you are 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 for 21 days after the last dose of Pemetrexed Accord. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before Pemetrexed Accord administration 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 inform 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 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 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 lungs).

Other side effects with Pemetrexed Accord 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

Abnormal blood tests showing reduced kidney function

Asthenia (fatigue)

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

Abnormal 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

Tearing

Dryness of the conjunctiva (membrane inside the eyelids and covering the white part of the eye) 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)

Decreased 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

Increased heart rate

Poor distribution of blood 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 from the anus

Bleeding in the gastrointestinal tract

Perforation of the intestine

Inflammation of the esophagus mucosa

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

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

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 spots

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 tubular cells that form the renal tubules

You may experience some of these symptoms and/or conditions. You should inform your doctor as soon as you start to experience 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, pharmacist or nurse. This includes any possible side effects 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 on the carton after EXP.

Store at a temperature below 25°C.

Solution for infusion: the medicine must be used immediately. When prepared as indicated, the chemical and physical stability of the solution for infusion is 72 hours at room temperature.

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 contents and additional information

Composition of Pemetrexed Accord

The active substance is pemetrexed. One ml of concentrate contains pemetrexed disodium hemipentahydrate equivalent to 25 mg of pemetrexed.

A 4 ml vial of concentrate contains pemetrexed disodium hemipentahydrate equivalent to 100 mg of pemetrexed.

A 20 ml vial of concentrate contains pemetrexed disodium hemipentahydrate equivalent to 500 mg of pemetrexed.

A 34 ml vial of concentrate contains pemetrexed disodium hemipentahydrate equivalent to 850 mg of pemetrexed.

A 40 ml vial of concentrate contains pemetrexed disodium hemipentahydrate equivalent to 1000 mg of pemetrexed.

The other components are citric acid, L-methionine, monothioglycerol, sodium hydroxide, concentrated hydrochloric acid, and water for injectable preparations (see section 2 "Pemetrexed Accord contains sodium").

Appearance of Pemetrexed Accord and container contents

Pemetrexed Accord is a concentrate for solution for infusion in a glass vial. It is a clear, colorless to pale yellow solution.

Each pack of Pemetrexed Accord contains a vial of 4 ml, 20 ml, 34 ml or 40 ml of concentrate.

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 Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice, Poland

LABORATORI FUNDACIÓ DAU

C/ C, 12-14 Pol. Ind. Zona Franca, Barcelona, 08040, Spain

Date of last revision of this prospectus:

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/

This information is intended only for doctors or healthcare professionals:

Instructions for use and handling and disposal

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

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

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

1. The prepared pemetrexed infusion solution, as 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 drugs should be inspected visually prior to administration to rule out the appearance of particles or color alteration. If particles are observed, the drug should not be administered.

1. Pemetrexed solutions are for single use. The drug and unused material should be discarded according to local requirements.

Storage

The chemical and physical stability in use of pemetrexed infusion solutions has been demonstrated for 72 hours at a temperature of 20°C to 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 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 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 rinsed with abundant 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 usual clinical practice with other non-vesicant drugs.