Label: information for the user

ALIMTA 100mg powder for concentrate for solution for infusion

ALIMTA 500mg powder for concentrate for solution for infusion

pemetrexed

Read this label carefully before starting to receive this medication,because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

ALIMTA is a medication used for the treatment of cancer.

ALIMTA can be administered along with cisplatino, another anticancer medication, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lung lining, in patients who have not received prior chemotherapy.

ALIMTA can also be administered, along with cisplatino, for the initial treatment of patients in advanced stages of lung cancer.

Alimta may be prescribed 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 administered for the treatment of patients in advanced stages of lung cancer whose disease has progressed, who have already received initial chemotherapy treatment.

Do not use ALIMTA

• If you are allergic (hypersensitive) to pemetrexed or any of the other components of this medication (listed in section6).
• If you are breastfeeding, you must stop breastfeeding during treatment with ALIMTA.
• If you have recently been given or are to be given the yellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before ALIMTA is administered to you.

If you have had or have kidney problems, tell your doctor or hospital pharmacist as it may be possible that you cannot receive ALIMTA.

Before each infusion, you will have to give blood samples to evaluate if your renal and hepatic function is sufficient and to evaluate 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 ensure that you are properly hydrated and receive the appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are to receive radiation therapy, please consult with your doctor, as there may be an early or late reaction between the radiation and ALIMTA.

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

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

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

Children and adolescents

This medication should not be used in children or adolescents, as there is no experience with this medication in children and adolescents under 18years.

Use of ALIMTA with other medications

Inform your doctor if you are using pain or anti-inflammatory medications (such as nonsteroidal anti-inflammatory drugs or 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 ALIMTA infusion and/or your renal function, your doctor will advise you which medications you can use and when. If you are unsure, consult your doctor or pharmacist to see if any medication you are taking is an NSAID.

Inform your doctor or hospital pharmacist if you are using or have recently used other medications, including those obtained without a prescription.

Pregnancy

If you are pregnant, think you may be pregnant, or intend to become pregnant,inform your doctor. During pregnancy, the use of ALIMTA should be avoided. Your doctor will inform you of the possible risks of taking ALIMTA during pregnancy. Women should use effective contraceptive methods during treatment with ALIMTA and for 6months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with ALIMTA, breastfeeding should be interrupted.

Fertility

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

Driving and operating machinery

ALIMTA may make you feel tired. Be careful when driving a vehicle or operating machinery.

ALIMTA contains sodium

ALIMTA 100mg powder for concentrate for solution for infusion

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

ALIMTA500mg powder for concentrate for solution for infusion

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

The dose of ALIMTA is 500 milligrams per square meter of the surface area of your body. 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 overall condition. The hospital pharmacist, nurse, or doctor will have mixed the ALIMTA powder with a 9 mg/ml (0.9%) sodium chloride solution for injection before it is administered to you.

You will always receive ALIMTA through an infusion (IV) 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 administered through an infusion in one of your veins and is given approximately 30 minutes after you have finished the ALIMTA infusion. The cisplatin infusion lasts approximately two hours.

You should normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe you some steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will have to take the day before, the same day, and the day after treatment with ALIMTA. Your doctor gives you this medication to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.

Vitamin supplement: Your doctor will prescribe you oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1000 micrograms) that you must take once a day while taking ALIMTA. You should take at least five doses during the seven days before the first dose of ALIMTA. You should continue taking folic acid for 21 days after the last dose of ALIMTA. You will also receive an injection of vitamin B12 (1000 micrograms) the week before administration of ALIMTA and approximately every 9 weeks (corresponding to 3 cycles of treatment with ALIMTA). Vitamin B12 and folic acid are given to reduce possible toxic effects of cancer treatment.

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

Like all medicines, this medicine can cause side 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 or very frequent, respectively): if you have a temperature of 38°C or higher, sweating, or other signs of infection (since you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and cause death.
• If you start to feel chest pain (frequent) or your heart rate is faster (infrequent).
• If you have pain, redness, swelling, or sores in your mouth (very frequent).
• Allergic reaction: if you develop hives (very frequent), burning sensation, or itching (frequent), or fever (frequent). In rare cases, skin reactions can be severe and may cause death. Contact your doctor if you present severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you lack breath or are pale (because you have fewer hemoglobin than normal, which is very frequent).
• If you experience bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruises (because you have fewer platelets than normal, which is frequent).
• If you experience sudden difficulty breathing, intense chest pain, or coughing up blood in your sputum (infrequent) (which may indicate that there is a blood clot in the pulmonary veins).

The side effects of ALIMTA may include:

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

Infection

Pharyngitis (sore throat)

Low count of neutrophil granulocytes (a type of white blood cell)

Low white blood cell count

Low hemoglobin levels

Mouth pain, redness, swelling, or sores

Loss of appetite

Vomiting

Diarrhea

Nausea

Skin rash

Dry skin

Abnormal blood test results showing reduced kidney function

Weakness (fatigue)

Frequent (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

Fluid loss

Changes in taste

Muscle weakness and atrophy (wasting, mainly in arms and legs) due to nerve damage

Sensory nerve damage that may cause numbness, burning sensation, and unstable gait

Dizziness

Conjunctivitis (inflammation or swelling of the membrane covering the eyes and the white part of the eye)

Dry eyes

Watery eyes

Dryness of the conjunctiva (membrane inside 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

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

Heart failure (condition affecting the heart's pumping ability)

Irregular heart rhythm

Indigestion

Constipation

Abdominal pain

Liver: increased substances in the blood produced by the liver

Increased skin pigmentation

Itching skin

Rash on the body where each lesion resembles a target

Hair loss

Urticaria

Renal failure

Reduced kidney function

Fever

Pain

Excess fluid in the body tissue causing swelling

Chest pain

Inflammation and ulceration of the mucous membranes lining the digestive tract

Infrequent (may affect up to 1 in 100 people)

Reduced count 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)

Myocardial infarction

Coronary artery narrowing or blockage

Increased heart rate

Poor blood distribution to the extremities

Obstruction of 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

Inflammation of the esophageal mucosa

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

Inflammation, edema, erythema, and erosion of the esophageal mucosa surface caused by radiation therapy

Inflammation of the lung caused by radiation therapy

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)

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 eruptions and blisters on the legs, arms, and abdomen

Inflammation of the skin characterized by the presence of blisters filled with fluid

Skin fragility, blisters, and erosions, and skin scars

Redness, pain, and swelling mainly of the lower limbs

Inflammation of the skin and subcutaneous fat (pseudocellulitis)

Inflammation of the skin (dermatitis)

The skin becomes inflamed, itches, reddens, cracks, and becomes rough

Intensely itchy spots

Unknown frequency: the frequency cannot be estimated from available data

A type of diabetes primarily caused by kidney disease

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

You may experience some of these side effects and/or situations. 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 side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the vial label and on the packaging.

This medication does not require any special storage conditions.

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

This medication is for single use only. Unused solution must be disposed of according to local requirements.

Composition of ALIMTA

The active ingredient is pemetrexed.

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

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

After reconstitution, the solution contains 25mg/ml of pemetrexed. Prior to administration, a healthcare professional must perform another dilution.

The other components are mannitol, hydrochloric acid, and sodium hydroxide.

Appearance of the product and contents of the pack

ALIMTA is a lyophilized powder for concentrate for solution for infusion in a vial. It is a white to pale yellow or greenish-yellow powder.

It is available in packs of 1vial.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Eli Lilly Nederland B.V.

Papendorpseweg 83, 3528 BJ Utrecht

Netherlands

Responsible for manufacturing:

Lilly France S.A.S.

rue du Colonel Lilly

F-67640, Fegersheim

France

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorization holder.

Last review date of this leaflet: MM/AAAA

Further information on this medicinal product can be obtained by visiting the website of the European Medicines Agency: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 required. Each vial contains an excess of pemetrexed to facilitate the administration of the nominal required amount.

1. ALIMTA 100mg:

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

ALIMTA 500mg:

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

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

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

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

1. Parenteral medicines should be visually inspected prior to administration to discard the appearance of particles or color change. If particles are observed, the medicine should not be administered.

1. The pemetrexed solutions are for single use only. Dispose of the medicine and unused material according to local requirements.

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, wash with plenty of water. Pemetrexed is not a vesicant. 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 non-vesicant drugs.