Label: Information for the User

ALIMTA 100 mg powder for concentrate for solution for infusion

ALIMTA 500 mg powder for concentrate for solution for infusion

pemetrexed

Read this label carefully before starting to receive this medication, as 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 medicine (listed in section 6).
• if you are breastfeeding, you should 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 or have had kidney problems, tell your doctor or hospital pharmacist as it may be 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 your doctor, as there may be an early or late reaction between the radiation and ALIMTA.

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

If you have heart disease 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 should not be used in children or adolescents, as there is no experience with this medicine in children and adolescents under 18 years.

Use of ALIMTA with other medicines

Inform your doctor if you are using pain or anti-inflammatory medicines (such as non-steroidal 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 medicines you can use and when. If you are unsure, consult your doctor or hospital pharmacist to see if any medicine you are taking is an NSAID.

Inform your doctor or hospital pharmacist if you are using or have recently used other medicines, 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 6 months 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 3 months after treatment with ALIMTA, and therefore should use effective contraceptive methods during and for 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 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 100 mg 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 500 mg powder for concentrate for solution for infusion

This medicine contains 54 mg 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. They will measure your height and weight 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 sodium chloride solution for injection of 9 mg/ml (0.9%), 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 the 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, on 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 that 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 1,000 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 (1,000 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 (rare).
• If you have mouth pain, redness, swelling, or sores (very frequent).
• Allergic reaction: if you develop hives (very frequent), burning or itching sensation (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 (since 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 (since you have fewer platelets than normal, which is frequent).
• If you experience sudden difficulty breathing, intense chest pain, or coughing up blood (rare) (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

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 causing numbness, burning pain, 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

Rare (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

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

Pulmonary inflammation caused by radiation therapy

Very rare (may affect up to 1 in 10,000 people)

Red blood cell destruction

Anaphylactic shock (severe allergic reaction)

Inflammatory liver disease

Skin redness

Rash on the skin that develops in a previously irradiated area

Unknown frequency: the frequency cannot be estimated from available data

Type of diabetes primarily caused by kidney disease

Renal disorder involving the death of tubular epithelial cells forming 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 the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about 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 of the reconstituted and infusion solution in use is 24 hours in refrigeration.

This medication is for single use only. Unused solution must be disposed of in accordance with local requirements.

Composition of ALIMTA

The active ingredient 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. 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 solution for infusion in a vial. It is a white to pale yellow or yellowish-green powder.

It is available in packs of 1 vial.

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

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

Last update of this leaflet: MM/AAAA

For detailed information about this medicinal product, please consult the website of the European Medicines Agency:http://www.ema.europa.eu.

This information is intended solely for healthcare professionals:

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 number of vials of ALIMTA required. Each vial contains an excess of pemetrexed to facilitate the administration of the nominal required amount.

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

ALIMTA 500 mg: Reconstitute each vial of 500 mg with 20 ml of a sodium chloride 0.9 % solution (9 mg/ml), without preservatives, to obtain a solution containing 25 mg/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 yellowish-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 solution to 100 ml with a sodium chloride 0.9 % solution (9 mg/ml) without preservatives and administer as an intravenous infusion over 10 minutes.

1. The pemetrexed solution for infusion prepared according to the above indications 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 alteration of color. If particles are observed, the medicine should not be administered.

1. The pemetrexed solutions are for single use. The medicine and unused material should be disposed of 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 solutions for infusion. 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 abundant water. Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. 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.