ALIMTA 500 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

ALIMTA 100mg powder for concentrate for solution for infusion

ALIMTA 500mg powder for 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 further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is ALIMTA and what is it used for

ALIMTA is a medicine used to treat cancer.

ALIMTA 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.

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

ALIMTA 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.

ALIMTA 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 ALIMTA

Do not use ALIMTA

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

Warnings and precautions

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

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

Before each infusion, you will need 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 ALIMTA. 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 between radiation and ALIMTA may occur.

If you have recently been vaccinated, please consult your doctor, as this may cause a negative effect with ALIMTA.

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 ALIMTA.

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.

Using ALIMTA 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 ALIMTA 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 or hospital pharmacist if you are using or have recently used 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, tell your doctor. ALIMTA should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking ALIMTA during pregnancy. Women must use effective contraceptive methods during treatment with ALIMTA and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, tell your doctor.

During treatment with ALIMTA, breastfeeding should be stopped.

Fertility

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

Driving and using machines

ALIMTA may make you feel tired. Be careful when driving a vehicle or using machines.

ALIMTA contains sodium

ALIMTA 100mg powder for concentrate for solution for infusion

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free".

ALIMTA 500mg powder for concentrate for solution for infusion

This medicine contains 54 mg of sodium (main component of table/cooking salt) in each vial. This is equivalent to 2.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use ALIMTA

The dose of ALIMTA 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 mixed the ALIMTA powder with a sodium chloride injection solution 9 mg/ml (0.9%) before it is given to you.

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

When using ALIMTA 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 ALIMTA 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 will need to take the day before, the day of, and the day after treatment with ALIMTA. 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 1000 micrograms) that you should take once a day while you are taking ALIMTA. You should take at least 5 doses during the 7 days before the first dose of ALIMTA. You should continue taking folic acid during 21 days after the last dose of ALIMTA. You will also receive a vitamin B12 injection (1000 micrograms) in the week before ALIMTA administration and then approximately every 9 weeks (corresponding to 3 cycles of treatment with ALIMTA). 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 or very frequent, respectively): if you have a temperature of 38°C or higher, sweating, or other signs of infection (as you may have a lower than normal number of white blood cells, 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 a lower than normal number of red blood cells, 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 a lower than normal number of platelets, 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).

Side effects with ALIMTA 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

Lack of appetite

Vomiting

Diarrhea

Nausea

Rash

Scaly skin

Changes in blood tests that show reduced kidney function

Weakness (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

Changes in 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 gait

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

Ocular disorder with dryness, tearing, irritation, and/or pain

Heart failure (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 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)

Decrease in the 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 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

Loss of bright red blood through 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 mucosal surface of the esophagus caused by radiotherapy

Inflammation of the lung caused by radiotherapy

Rare (may affect up to 1 in 1000 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 patches

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 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, even if they are not listed in this leaflet. You can also report them directly to the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of ALIMTA

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 of the vial and on the carton.

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.

This medicine is for single use only. The unused solution should be discarded in accordance with local requirements.

6. Contents of the pack and additional information

Composition of ALIMTA

The active substance is pemetrexed.

ALIMTA 100 mg: Each vial contains 100 mg of pemetrexed (as pemetrexed disodium).

ALIMTA 500 mg: Each vial contains 500 mg of pemetrexed (as pemetrexed disodium).

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.

Appearance and pack contents of the product

ALIMTA is a powder for concentrate for solution for infusion in a vial. It is a lyophilized powder, white to pale yellow or yellowish-green in color.

It is available in packs of 1 vial.

Only certain pack sizes may be marketed.

Marketing authorisation holder

Eli Lilly Nederland B.V.

Papendorpseweg 83, 3528 BJ Utrecht

Netherlands

Manufacturer

Lilly France S.A.S.

rue du Colonel Lilly

F-67640, Fegersheim

France

For further information on this medicinal product, please contact the local representative of the marketing authorisation holder.

Date of last revision of this leaflet: MM/YYYY

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended for healthcare professionals only:

Instructions for use, handling, and disposal

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

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

1. ALIMTA 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.

ALIMTA 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.

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, which does not negatively affect the quality of the product. The pH of the reconstituted solution is between 6.6 and 7.8. Further 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 administered as an intravenous infusion over 10 minutes.

1. The prepared pemetrexed infusion solution is compatible with polyvinyl chloride and polyolefin infusion systems and bags. Pemetrexed is incompatible with diluents containing calcium, including Ringer's lactate for injection and Ringer's injection.

1. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. 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.

Precautions in preparation and administration:As with any 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 flushed 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.