Alimta 500 mg powder for concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: 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 the entire leaflet carefully before you start receiving this medicine, because it contains important information for you.

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

Contents of the leaflet

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

1. What ALIMTA is and what it is used for

ALIMTA is a medicine used to treat cancer.

ALIMTA may be given together with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a type of cancer affecting the lining of the lung, in patients who have not previously received chemotherapy.

ALIMTA may also be given together with cisplatin as initial treatment for patients with advanced-stage lung cancer.

ALIMTA may be prescribed to you if you have advanced-stage lung cancer and your disease has responded to treatment or has remained stable after initial chemotherapy.

ALIMTA may also be given for the treatment of patients with advanced-stage lung cancer whose disease has progressed after prior initial chemotherapy treatment.

2. What you need to know before using ALIMTA

Do not use ALIMTA

• if you are allergic (hypersensitive) to pemetrexed or to 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 scheduled to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or hospital pharmacist before receiving ALIMTA.

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

Before each infusion, you will need to provide blood samples to assess whether your kidney and liver function are adequate and to evaluate whether you have enough blood cells to receive ALIMTA. Your doctor may decide to adjust 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 you are properly hydrated and will administer appropriate treatment before and after cisplatin to prevent vomiting.

If you have received or are scheduled to receive radiotherapy, please consult your doctor, as there may be an early or delayed interaction between radiation and ALIMTA.

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

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

If you have fluid accumulation 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 of age.

Use of ALIMTA with other medicines

Inform your doctor if you are taking pain or anti-inflammatory (swelling) medicines, such as medicines known as "non-steroidal anti-inflammatory drugs" (NSAIDs), including those obtained without a prescription (such as ibuprofen). There are many types of NSAIDs with different durations of action. Based on the date of your ALIMTA infusion and/or your kidney function status, your doctor will advise you which medicines you may take and when. If you are unsure, consult your doctor or pharmacist to determine whether any medicine you are taking is an NSAID.

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

Pregnancy

If you are pregnant, think you might be pregnant, or plan to become pregnant, inform your doctor. Use of ALIMTA should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking ALIMTA during pregnancy. Women must use effective contraception during treatment with ALIMTA and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding must be discontinued during treatment with ALIMTA.

Fertility

Male patients are advised not to father a child during and for 3 months after treatment with ALIMTA, and therefore must use effective contraception during and for 3 months after treatment with ALIMTA. If you wish to father a child during treatment or within 3 months after treatment, seek advice from your doctor or pharmacist. ALIMTA may affect your ability to have children. Speak with your doctor for advice on sperm preservation before starting treatment.

Driving and use of machines

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

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; 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) per vial. This corresponds to 2.7% of the maximum daily sodium intake recommended 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 determine the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell counts and your general condition. The hospital pharmacist, nurse, or doctor will have reconstituted the ALIMTA powder with a sodium chloride 9 mg/mL (0.9%) injection solution prior to administration.

You will always receive ALIMTA as an intravenous infusion (drip) into 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 by intravenous infusion and is given approximately 30 minutes after the ALIMTA infusion has finished. The cisplatin infusion lasts approximately two hours.

You should normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) to be taken the day before, the day of, and the day after ALIMTA treatment. Your doctor prescribes 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 oral folic acid (vitamin) or a multivitamin containing folic acid (350 to 1000 micrograms), which you must take once daily while receiving ALIMTA. You should take at least five doses during the seven days prior to your first dose of ALIMTA. You must continue taking folic acid for 21 days after your last dose of ALIMTA. Additionally, you will receive a vitamin B12 injection (1000 micrograms) during the week before starting ALIMTA, and then approximately every 9 weeks (corresponding to 3 treatment cycles of ALIMTA). Vitamin B12 and folic acid are given to reduce potential toxic effects of the cancer treatment.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

You must inform your doctor immediately if you notice any of the following symptoms:

• Fever or infection (common and very common, 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 common). Infections (sepsis) can be severe and may cause death.
• If you begin to feel chest pain (common) or your heartbeat becomes faster (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), burning sensation or itching (common), or fever (common). Skin reactions may rarely be severe and may cause death. Contact your doctor if you develop severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, are short of breath, or appear pale (due to lower than normal hemoglobin levels, which is very common).
• If you experience bleeding from the gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruising (due to lower than normal platelet counts, which is common).
• If you suddenly experience difficulty breathing, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the lung veins).

Adverse effects with ALIMTA may include:

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

Infection
Pharyngitis (sore throat)
Low neutrophil granulocyte 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
Skin rash
Scaly skin
Abnormal blood tests showing reduced kidney function

Asthenia (tiredness)

Common (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
Loss of body fluids
Changes in taste sensation
Nerve damage causing muscle weakness and atrophy (mainly in arms and legs)
Sensory nerve damage causing loss of sensation, burning pain, and unsteady gait
Dizziness
Inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye)
Dry eyes
Watery eyes
Dryness of the conjunctiva (the inner membrane of the eyelids and covering the white part of the eye) and cornea (the transparent layer in front of the iris and pupil)
Eyelid swelling
Eye disorder with dryness, tearing, irritation, and/or pain
Heart failure (a condition affecting the heart muscle's ability to pump)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increased levels of liver-produced chemicals in the blood
Increased skin pigmentation
Itchy skin
Rash where each lesion resembles a target
Hair loss
Hives
Kidney failure
Reduced kidney function
Fever
Pain
Excess fluid in body tissues causing swelling
Chest pain
Inflammation and ulceration of the mucous membranes lining the digestive tract

Uncommon (may affect up to 1 in 100 people)

Reduction in red blood cells, white blood cells, and platelets
Ischemia or poor blood supply
Ischemia due to blockage of a cerebral artery
Intracranial hemorrhage
Angina (chest pain caused by reduced blood flow to the heart)
Infarction
Narrowing or blockage of the coronary arteries
Increased heart rate
Poor blood distribution to limbs
Blockage in one of the pulmonary arteries in the lungs
Inflammation and scarring of the lung mucosa causing breathing problems
Passing bright red blood from 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 (observed only in combination with cisplatin)
Inflammation, edema, erythema, and erosion of the esophageal mucosal surface caused by radiotherapy
Lung inflammation 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
Skin rash developing 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 rashes and blisters on the legs, arms, and abdomen
Skin inflammation characterized by the presence of fluid-filled blisters
Skin fragility, blistering, erosions, and scarring of the skin
Redness, pain, and swelling mainly in the lower limbs
Inflammation of the skin and underlying fat (pseudocellulitis)
Skin inflammation (dermatitis)
Skin becomes inflamed, itchy, red, cracked, and rough
Intensely itchy spots

Frequency not known: frequency cannot be estimated from available data

A type of diabetes mainly resulting from kidney disease
Kidney disorder involving death of the tubular epithelial cells forming the renal tubules

You may experience one or more of these symptoms and/or conditions. You must inform your doctor as soon as you begin to experience any of these adverse effects.

If you are concerned about any adverse effect, consult your doctor.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse 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 stated on the vial label and on the outer packaging.

This medicine requires no special storage conditions.

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

This medicine is for single use only. Any unused solution should be discarded according to local requirements.

6. Contents of the pack and other 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. A further dilution by a healthcare professional is required before administration.

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

Appearance of the product and contents of the pack

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

It is available in packs of 1 vial.

Some pack sizes may not be marketed.

Marketing Authorization Holder

Eli Lilly Nederland B.V.

Papendorpseweg 83, 3528 BJ Utrecht

The Netherlands

Manufacturer:

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.

Date of the most recent review of this summary: MM/YYYY

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

This information is intended for medical or healthcare professionals only:

Instructions for use, handling, and disposal

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

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

3. ALIMTA 100 mg:

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

Gently shake the vial until the powder is completely dissolved. The resulting solution is clear, with a color range varying from colorless to yellow or yellow-green, without negatively affecting the product's quality. 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 must be diluted to 100 ml with 0.9% sodium chloride injection solution (9 mg/ml), without preservatives, and administered as an intravenous infusion over 10 minutes.

2. The pemetrexed infusion solution prepared as described above is compatible with polyvinyl chloride and polyolefin infusion bags and systems. Pemetrexed is incompatible with diluents containing calcium, including injection lactated Ringer's solution and injection Ringer's solution.

3. Parenteral medicines should be visually inspected before administration to check for the presence of particles or discoloration. If particles are observed, the medicine must not be administered.

4. Pemetrexed solutions are for single use only. Unused medicine and materials must be discarded according to local requirements.

Precautions in preparation and administration: As with any other potentially toxic antineoplastic agent, special care should be taken in handling and preparing pemetrexed infusion solutions. The use of gloves is recommended. If pemetrexed solutions come into contact with the skin, wash immediately and thoroughly with soap and water. If pemetrexed solutions come into contact with mucous membranes, rinse thoroughly with 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 managed according to standard clinical practice for non-vesicant drugs.