ALIMTA 500 mg Proszek Do Sporządzania Roztworu Do Wstrzykiwań

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1. ALIMTA 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion
   1. What is ALIMTA and what is it used for
   2. What you need to know before you take ALIMTA
   3. How to take ALIMTA
   4. Possible side effects
   5. How to store ALIMTA
   6. Package contents and other information

ALIMTA 100 mg powder for concentrate for solution for infusion, 500 mg powder for concentrate for solution for infusion

pemetrexed

Read this leaflet carefully before you receive this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is ALIMTA and what is it used for

ALIMTA is a medicine used in the treatment of tumors.
ALIMTA is administered in association with cisplatin, another anticancer drug, as
treatment for malignant pleural mesothelioma, a form of tumor that affects the tissue
lining the lungs, to patients who have not received previous chemotherapy.
Furthermore ALIMTA, in association with cisplatin, is administered for first-line therapy in
patients affected by advanced stage lung cancer.
ALIMTA may be prescribed in case of advanced stage lung cancer if the disease has
responded to treatment or if it remains largely unchanged after initial chemotherapy.
Furthermore ALIMTA is a treatment for patients affected by advanced stage lung cancer whose
disease has progressed after a previous initial chemotherapeutic treatment.

2. What you need to know before you take ALIMTA

Do not take 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 had or are about to have the yellow fever vaccination.

Warnings and precautions
Talk to your doctor or hospital pharmacist before receiving ALIMTA.
If you have or have had kidney problems, tell your doctor or hospital pharmacist as you may
not be able to receive ALIMTA.
Before each infusion, blood tests will be performed to assess whether you have sufficient
liver and kidney function and to check that you have enough cells in your blood to receive
ALIMTA. The doctor may decide to change the dose or delay treatment depending on your
general condition and if the blood test (white blood cells and platelets) results are inadequate
(too low). Also, if you are receiving cisplatin, the doctor must ensure that you are
adequately hydrated and that you receive appropriate treatment before and after receiving cisplatin
to prevent vomiting.
If you have had or will be undergoing radiation treatment, tell your doctor, as
with ALIMTA, an early or delayed reaction due to radiation treatment may occur.
If you have been vaccinated recently, tell your doctor, as with ALIMTA this could
cause adverse effects.
If you have heart disease or a history of heart disease, tell your doctor.
If you have fluid buildup around your lungs, the doctor may decide to remove the
fluid before administering ALIMTA.

Children and adolescents
This medicine should not be used in children and adolescents because there is no experience in
children and adolescents under 18 years of age.

Other medicines and ALIMTA
Tell your doctor if you are taking any medicine for pain or inflammation (swelling), such as medicines called “non-steroidal anti-inflammatory drugs”
(NSAIDs), including over-the-counter medicines (such as ibuprofen). There are
many types of NSAIDs with different durations of activity. Based on the planned date for the ALIMTA
infusion and/or your kidney function, the doctor will advise you on which medicines you can take and when
you can take them. If you are unsure, ask your doctor or pharmacist if any of your medicines is an
NSAID.
Tell your doctor if you are taking medicines called proton pump inhibitors (omeprazole,
esomeprazole, lansoprazole, pantoprazole and rabeprazole) used to treat heartburn and
acid reflux.
Tell your doctor or hospital pharmacist if you are taking or have recently taken any
other medicines, even those available without a prescription.

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, tell your doctor. The use
of ALIMTA during pregnancy should be avoided. The doctor will discuss with you the potential risk
of taking ALIMTA during pregnancy. Women must use an effective method of contraception
during treatment with ALIMTA and for 6 months after receiving the last dose.

Breastfeeding
If you are breastfeeding, tell your doctor.
Breastfeeding must be stopped during treatment with ALIMTA.

Fertility
Men are advised not to father a child during treatment with ALIMTA for up to 3 months
afterwards and therefore to use effective contraception during treatment with ALIMTA and for up to 3
months afterwards. If you wish to father a child during treatment or within 3 months afterwards, ask
for advice from your doctor or pharmacist. ALIMTA may affect your ability to have children. Talk
to your doctor for advice on ways to preserve sperm before starting
therapy.

Driving and operating machinery
ALIMTA may cause fatigue. Be careful when driving a vehicle or operating machinery.

ALIMTA contains sodium

ALIMTA 100 mg powder concentrate for solution for infusion
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is essentially
“sodium-free”.

ALIMTA 500 mg powder concentrate for solution for infusion
This medicine contains 54 mg of sodium (the main component of table salt) per
vial. This is equivalent to 2.7% of the maximum recommended daily intake of sodium for a
adult from the diet.

3. How to take ALIMTA

The dose of ALIMTA is 500 mg per each square meter of body surface area. Your height and weight will be measured to calculate your body surface area. The doctor will use this body surface area to calculate the right dose for you. This dosage may be adjusted or treatment may be delayed depending on blood tests and your overall condition. A hospital pharmacist, nurse or doctor will have mixed the ALIMTA powder with a solution of sodium chloride 9 mg/ml (0.9 %) for injectable preparations before administering it to you.
You will receive ALIMTA always by infusion into a vein. The infusion will last approximately 10 minutes.
When ALIMTA is used in combination with cisplatin:
The doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also administered by infusion into a vein, approximately 30 minutes after the ALIMTA infusion has been completed. The cisplatin infusion will last approximately 2 hours.
Usually you should receive the infusion once every 3 weeks.
Additional medicines:
Corticosteroids: the 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 ALIMTA. This medicine is given to you to reduce the frequency and severity of skin reactions that may occur during cancer treatment.
Vitamin supplement: the doctor will prescribe folic acid (vitamin) or a multivitamin product containing folic acid (350-1000 micrograms) orally that you must take once a day while you are being treated with ALIMTA. You must take at least 5 doses during the seven days before the first dose of ALIMTA. You must continue to take folic acid for 21 days after the last dose of ALIMTA. You will also receive an injection of vitamin B (1000 micrograms) in the week before the administration of ALIMTA and then approximately every 9 weeks (corresponding to 3 treatment cycles with ALIMTA). Vitamin B and folic acid are given to you to reduce the possible toxic effects of cancer treatment.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
You should immediately contact your doctor if you notice any of the following side effects:

• Fever or infection (common or very common, respectively): if you have a body 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). Infection (sepsis) can be serious and may lead to death.
• If you begin to experience chest pain (common) or an increased heart rate (uncommon).
• If you have pain, redness, swelling, or sores in your mouth (very common).
• Allergic reaction: if you develop a skin rash (very common)/burning or tingling sensation (common) or fever (common). Rarely, skin reactions can be severe and may lead to death. Contact your doctor if a severe rash, or itching, or blisters appear (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired, feel faint, feel short of breath easily, or are pale (as you may have less hemoglobin than normal, which is very common).
• If you experience bleeding from the gums, nose, or mouth, or any bleeding that does not tend to stop, reddish or slightly pink urine, unexplained bruising (as you may have fewer platelets than normal, which is common).
• If you experience sudden shortness of breath, severe chest pain, or cough up blood in your sputum (uncommon) (may indicate a blood clot in the pulmonary vessels).

Side effects with ALIMTA may include:

Very common (may affect more than 1 in 10 people)
Infection
Pharyngitis (sore throat)
Low number of neutrophils (a type of white blood cells)
Low white blood cell count
Low level of hemoglobin
Pain, redness, swelling, or ulcers in the mouth
Loss of appetite
Vomiting
Diarrhea
Nausea
Skin redness
Skin peeling
Abnormal blood tests showing reduced kidney function
Fatigue (tiredness)

Common (may affect up to 1 in 10 people)
Bloodstream infection
Fever with low number of neutrophils (a type of white blood cells)
Low platelet count
Allergic reactions
Loss of body fluids
Taste alteration
Damage to motor nerves that may cause muscle stiffness and atrophy that can cause muscle weakness and atrophy (wasting) primarily in the arms and legs
Damage to sensory nerves that can cause loss of sensation, burning, and unsteady gait
Dizziness
Inflammation or swelling of the conjunctiva (the membrane that lines the eyelids and covers the white part of the eye)
Dry eye
Excessive tearing
Dryness of the conjunctiva (the membrane that lines the eyelids and covers the white part of the eye) and the cornea (the clear layer in front of the iris and pupil).
Swelling of the eyelids
Eye disorders with dryness, tearing, irritation and/or pain
Heart failure (a condition that affects the ability of the heart muscle to pump)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increase in blood levels of chemicals produced by the liver
Increased skin pigmentation
Skin itching
Widespread red spots
Hair loss
Hives
Kidneys stopping working
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 the number of white and red blood cells and platelets
Stroke
Type of stroke when an artery in the brain is blocked
Bleeding in the skull
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 the lungs, of one of the pulmonary arteries
Inflammation and scarring of the lining of the lungs with breathing problems
Bright red blood from the anus
Bleeding from the gastrointestinal tract
Rupture of the intestine
Inflammation of the lining of the esophagus
Inflammation of the lining 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 surface of the mucosa of the esophagus caused by radiation therapy
Inflammation of the lung caused by radiation therapy

Rare (may affect up to 1 in 1,000 people)
Destruction of red blood cells
Anaphylactic shock (severe allergic reaction)
Inflammatory condition of the liver
Skin redness
Sudden skin redness that develops in a previously irradiated area

Very Rare (may affect up to 1 in 10,000 people)
Infection of the skin and soft tissues
Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that may be life-threatening)
Toxic epidermal necrolysis (a type of severe skin reaction that may lead to life-threatening conditions)
Autoimmune disorders resulting in sudden redness of the skin and blisters on the legs, arms, and abdomen
Inflammation of the skin characterized by the presence of blisters that fill with fluid
Fragility of the skin, blisters and erosion and scarring of the skin
Redness, pain and swelling mainly of the lower limbs
Inflammation of the skin and fat under the skin (pseudocellulitis)
Inflammation of the skin (dermatitis)
Skin that becomes inflamed, itchy, red, cracked and rough
Intensely itchy spots

Not known: frequency cannot be estimated based on available data
Form of diabetes primarily due to kidney disease
Kidney disorders involving the death of tubular epithelial cells that form the kidney tubules
You may experience one of these symptoms and/or conditions. You should tell your doctor as soon as possible when you begin to experience any of these side effects.
If you have any doubts about any side effect, talk to your doctor.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store 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 vial label and on the
pack.
This medicine does not require special storage conditions.
Reconstituted and infusion solutions: the product must be used immediately. If prepared
as directed, the chemical and physical stability during use of reconstituted and
infusion pemetrexed solutions has been demonstrated for 24 hours at refrigerated temperature.
This medicine is for single use only, unused solution must be disposed of in
accordance with local legal requirements.

6. Package contents and other information

What ALIMTA contains
The active ingredient is pemetrexed.
ALIMTA 100 mg: Each vial contains 100 milligrams of pemetrexed (as pemetrexed
disodium)
ALIMTA 500 mg: Each vial contains 500 milligrams of pemetrexed (as pemetrexed
disodium)
After reconstitution, the solution contains 25 mg/ml of pemetrexed. Further dilution by healthcare professionals is
necessary before administration.
The other ingredients are mannitol, hydrochloric acid and sodium hydroxide.

Description of the appearance of ALIMTA and contents of the pack
ALIMTA is a powder for concentrate for solution for infusion in a vial. It is a
lyophilized powder of variable color from white to pale yellow or yellowish-green.
It is available in packs of 1 vial.
Not all pack sizes may be marketed.

Marketing authorization 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 medicine, contact the local representative of the marketing
authorization holder:

Belgique/België/Belgien
Eli Lilly Benelux S.A./N.V.
Tél/Tel: + 32-(0)2 548 84 84

Lietuva
Eli Lilly Lietuva
Tel. +370 (5) 2649600

България
TP "Eli Lilly Nederland" B.V. - България
tel. + 359 2 491 41 40

Luxembourg/Luxemburg
Eli Lilly Benelux S.A./N.V.
Tél/Tel: + 32-(0)2 548 84 84

Česká republika
ELI LILLY ČR, s.r.o.
Tel: + 420 234 664 111

Magyarország
Lilly Hungária Kft.
Tel: + 36 1 328 5100

Danmark
Eli Lilly Danmark A/S
Tlf: +45 45 26 6000

Malta
Charles de Giorgio Ltd.
Tel: + 356 25600 500

Deutschland
Lilly Deutschland GmbH
Tel. + 49-(0) 6172 273 2222

Nederland
Eli Lilly Nederland B.V.
Tel: + 31-(0) 30 60 25 800

Eesti
Eli Lilly Nederland B.V.
Tel: +372 6817 280

Norge
Eli Lilly Norge A.S.
Tlf: + 47 22 88 18 00

Ελλάδα
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε.
Τηλ: +30 210 629 4600

Österreich
Eli Lilly Ges. m.b.H.
Tel: + 43-(0) 1 711 780

España
Lilly S.A.
Tel: + 34 91-663 50 00

Polska
Eli Lilly Polska Sp. z o.o.
Tel.: +48 22 440 33 00

France
Lilly France
Tél: +33-(0) 1 55 49 34 34

Portugal
Lilly Portugal - Produtos Farmacêuticos, Lda
Tel: + 351-21-4126600

Hrvatska
Eli Lilly Hrvatska d.o.o.
Tel: +385 1 2350 999

România
Eli Lilly România S.R.L.
Tel: + 40 21 4023000

Ireland
Eli Lilly and Company (Ireland) Limited
Tel: + 353-(0) 1 661 4377

Slovenija
Eli Lilly farmacevtska družba, d.o.o.
Tel: +386 (0)1 580 00 10

Ísland
Icepharma hf.
Sími + 354 540 8000

Slovenská republika
Eli Lilly Slovakia s.r.o.
Tel: + 421 220 663 111

Italia
Eli Lilly Italia S.p.A.
Tel: + 39- 055 42571

Suomi/Finland
Oy Eli Lilly Finland Ab
Puh/Tel: + 358-(0) 9 85 45 250

Κύπρος
Phadisco Ltd
Τηλ: +357 22 715000

Sverige
Eli Lilly Sweden AB
Tel: + 46-(0) 8 7378800

Latvija
Eli Lilly (Suisse) S.A Pārstāvniecība Latvijā
Tel: +371 6 7364000
More detailed information on this medicine is available on the website of the European
Medicines Agency, https://www.ema.europa.eu/
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The following information is intended exclusively for physicians or healthcare professionals:
Instructions for use, handling and disposal

• 1. Use aseptic techniques during reconstitution and further dilution of pemetrexed for the administration of the intravenous infusion.
• 2. Calculate the dose and the number of vials of ALIMTA needed. Each vial contains an excess of pemetrexed to facilitate dispensing the amount indicated on the label.
• 3. ALIMTA 100 mg: Reconstitute each 100 mg vial with 4.2 ml of sodium chloride 9 mg/ml (0.9 %) solution for injections, without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed. ALIMTA 500 mg: Reconstitute each 500 mg vial with 20 ml of sodium chloride 9 mg/ml (0.9 %) solution for injections, without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed. Gently shake each vial until the powder is completely dissolved. The resulting solution is clear and is variable from colorless to yellow or yellowish-green without negatively affecting the quality of the product. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.
• 4. The appropriate volume of reconstituted pemetrexed solution must be further diluted to 100 ml with sodium chloride 9 mg/ml (0.9 %) solution for injections, without preservatives, and administered by intravenous infusion over 10 minutes.
• 5. Pemetrexed infusion solutions prepared as described above are compatible with polyvinyl chloride and polyolefin coated infusion bags and administration sets. Pemetrexed is incompatible with solvents containing calcium, including Ringer's lactate for injections and Ringer's solution for injections.
• 6. Before administration, parenteral products must be visually inspected for particles and color changes. Do not administer if particles are observed.
• 7. Pemetrexed solutions are for single use only. Unused product and waste materials from this medicine must be disposed of in accordance with local legal requirements.

Precautions for preparation and administration:As with other potentially toxic antitumor agents,
caution should be exercised when handling and preparing pemetrexed infusion solutions. The use of
gloves is recommended. If a pemetrexed solution comes 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 vesicant. There is no specific antidote for pemetrexed extravasation. Some
cases of pemetrexed extravasation have been reported that were not considered serious by the investigator. Extravasation
should be managed according to standard procedures as for other non-vesicant agents.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Report (PSUR) for pemetrexed, the scientific conclusions of the PRAC are as follows:
In light of the available data on the pharmacokinetics of pemetrexed, considering that in vitro studies
have indicated that pemetrexed is actively secreted by the organic anion transporter OAT3 (organic anion
transporter 3) and considering the IC50 values for proton pump inhibitors, the PRAC considers that a drug-drug
interaction between proton pump inhibitors and pemetrexed is at least a reasonable possibility. The PRAC
concluded that the product information for medicines containing pemetrexed should be amended accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products
(CHMP) agrees with the related overall conclusions and with the justification of the recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on pemetrexed, the CHMP considers that the benefit/risk ratio of the
medicines containing pemetrexed remains unchanged, subject to the proposed changes to the product
information.
The CHMP recommends the variation of the terms of the marketing authorisation.