PEMETREXED 25 mg /Ml Koncentrat Do Sporządzania Roztworu Do Infuzji

Treść ulotki

1. Pemetrexed Sandoz BV 25 mg/ml concentrate for solution for infusion
   1. What is Pemetrexed Sandoz BV and what is it used for
   2. What you need to know before using Pemetrexed Sandoz BV
   3. How to use Pemetrexed Sandoz BV
   4. Possible side effects
   5. How to store Pemetrexed Sandoz BV
   6. Contents of the pack and other information

Pemetrexed Sandoz BV 25 mg/ml concentrate for solution for infusion

Generic medicine

Read this leaflet carefully before you start using 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.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even if not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Pemetrexed Sandoz BV and what is it used for

Pemetrexed Sandoz BV is a medicine used in the treatment of tumors.
Pemetrexed Sandoz BV is administered in association with cisplatin, another anticancer drug,
as treatment for malignant pleural mesothelioma, a form of cancer that affects the tissue
lining the lungs, in patients who have not received previous chemotherapy.
Furthermore Pemetrexed Sandoz BV in association with cisplatin, is administered for first-line therapy in
patients affected by advanced stage lung cancer.
Pemetrexed Sandoz BV 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 Pemetrexed Sandoz BV is a treatment for patients affected by advanced stage
lung cancer whose disease has progressed after a previous initial chemotherapeutic treatment.
This medicine is only for use in adults.

2. What you need to know before using Pemetrexed Sandoz BV

Do not use Pemetrexed Sandoz BV:

• if you are allergic 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 Pemetrexed Sandoz BV.
• 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 Pemetrexed Sandoz BV.
If you have or have previously had kidney problems, tell your doctor or hospital pharmacist
because you may not be able to receive Pemetrexed Sandoz BV.
Before each infusion, you will have blood tests to assess whether you have sufficient
kidney and liver function and to check that you have enough cells in your blood to receive
Pemetrexed Sandoz BV. The doctor may decide to change the dose or delay treatment
depending on your general condition and if the number of cells in your blood is too
low. Also, if you are receiving cisplatin, the doctor will 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 having radiotherapy, tell your doctor, as Pemetrexed Sandoz BV may cause an early or delayed reaction due to radiotherapy.
If you have been vaccinated recently, tell your doctor, as Pemetrexed Sandoz BV may cause adverse effects.
If you have heart disease or a history of heart disease, tell your doctor.
If you have fluid build-up around your lungs, the doctor may decide to remove the
fluid before giving you Pemetrexed Sandoz BV.

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 Pemetrexed Sandoz BV
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 action. Based on the planned date for the
infusion of Pemetrexed Sandoz BV 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 or hospital pharmacist if you are taking or have recently taken any other
medicines, including over-the-counter medicines.

Pregnancy, breastfeeding and fertility

Pregnancy
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, tell your doctor.
The use of Pemetrexed Sandoz BV during pregnancy should be avoided. The doctor will talk to you
about the potential risk of taking Pemetrexed Sandoz BV during pregnancy.
Women must use effective contraception during treatment with
Pemetrexed Sandoz BV.

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

Fertility
Men are advised not to father a child during treatment with Pemetrexed Sandoz BV and
for up to 6 months afterwards and therefore to use effective contraception during treatment with
Pemetrexed Sandoz BV and for 6 months afterwards. If you wish to father a child during treatment
or within 6 months afterwards, ask your doctor or pharmacist for advice. You are advised to ask
about ways to store sperm before starting therapy.

Driving and using machines
Pemetrexed Sandoz BV can cause fatigue. Be careful when driving a vehicle or using
machines.

Pemetrexed Sandoz BV contains sodium and propylene glycol
Pemetrexed Sandoz BV 100 mg (4 ml vial):
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e. it is essentially
sodium-free. This medicine contains 200 mg of propylene glycol in each vial.
Pemetrexed Sandoz BV 500 mg (20 ml vial):
This medicine contains 55.6 mg of sodium (the main component of table salt) per vial.
This is equivalent to 3% of the recommended maximum daily intake of salt with the diet
of an adult. This medicine contains 1000 mg of propylene glycol in each vial.
Pemetrexed Sandoz BV 1000 mg (40 ml vial):
This medicine contains 111.2 mg of sodium (the main component of table salt) per vial.
This is equivalent to 6% of the recommended maximum daily intake of salt with the diet
of an adult. This medicine contains 2000 mg of propylene glycol in each vial.

3. How to use Pemetrexed Sandoz BV

Pemetrexed Sandoz BV must be administered only under the supervision of a doctor
qualified in the use of anticancer chemotherapy.
The dose of Pemetrexed Sandoz BV 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 Pemetrexed Sandoz
BV solution with a solution for injectable preparations of sodium chloride 9 mg/ml (0.9%) or glucose 50
mg/ml (5%) before administering it to you.
You will receive Pemetrexed Sandoz BV always by infusion into a vein. The infusion will last about 10
minutes.
When Pemetrexed Sandoz BV is used in combination with cisplatin:
The doctor or hospital pharmacist will calculate the dose you need based on your height and
your weight. Cisplatin is also administered by infusion into a vein, approximately 30 minutes after
the Pemetrexed Sandoz BV infusion is completed. The cisplatin infusion will last approximately 2 hours.
Normally 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 Pemetrexed Sandoz BV. This medicine is given to you to reduce the frequency and
severity of skin reactions that may occur during anticancer 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 Pemetrexed Sandoz BV. You must take at least 5 doses during the seven
days before the first dose of Pemetrexed Sandoz BV. You must continue to take folic acid
for 21 days after the last dose of Pemetrexed Sandoz BV. You will also receive an injection of vitamin
B (1000 micrograms) in the week before the administration of Pemetrexed Sandoz BV and
then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Sandoz BV). Vitamin B and folic acid are administered to you to reduce the possible toxic effects of anticancer
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 could lead to death.
• If you begin to experience chest pain(common) or have an increased heart rate (uncommon).
• If you have pain, redness, swellingor 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 could lead to death. Contact your doctor if a severe rash, or itching, or blisters(Stevens-Johnson syndrome or toxic epidermal necrolysis) appear.
• If you experience fatigue, feel faint, feel short of breatheasily or are pale (as you may have less hemoglobin than normal, which is very common).
• If you have bleeding from the gums, nose or mouthor 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 painor have blood in your sputum when coughing (uncommon) (may indicate a blood clot in the pulmonary vessels).

Side effects with Pemetrexed Sandoz BV 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 number of white blood cells
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 primary atrophy (wasting) in the arms and legs
Damage to sensory nerves that can cause loss of sensation, burning and unstable gait
Dizziness
Inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the
white part of the eye)
Dry eye
Excessive tearing
Dryness of the conjunctiva (the membrane lining the eyelids and covering 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 heart muscle's ability to pump)
Irregular heartbeat
Indigestion
Constipation
Abdominal pain
Liver: increased 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
Insufficient blood supply 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 1000 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)
Skin and soft tissue infection
Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that could be life-threatening)
Toxic epidermal necrolysis (a type of severe skin reaction that can lead to
life-threatening)
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 renal tubules
You may experience one of these symptoms and/or conditions. You should tell your doctor as soon as
possible when you start to have one 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. You can also report side effects directly through
the national reporting system at www.aifa.gov.it/content/come-segnalare-una-sospetta-
reazione-avversa .
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Pemetrexed Sandoz BV

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 pack and on the label after
Exp. The expiry date refers to the last day of that month.
Closed vial
Do not store above 25 °C. Store in the original package to protect
the medicine from light.
After first opening
The product must be used immediately. Unused portions of the product must be
discarded.
After dilution

100 mg vial
The stability of the solution prepared for infusion has been demonstrated for 3 days in a refrigerator at 2–
8°C, protected from light.

500 mg and 1000mg vial
The stability of the solution prepared for infusion has been demonstrated for 7 days at room
temperature protected from light and for 14 days in a refrigerator at 2°C–8°C, protected from light
From a microbiological point of view, the product must be used immediately. If not used
immediately, the storage times and conditions in use are the responsibility of the user
and should normally not exceed 24 hours at 2°C-8°C, unless the dilution has been
carried out under controlled and validated aseptic conditions.
Do not dispose of any medicine in the wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Pemetrexed Sandoz BV contains
The active substance is pemetrexed (as pemetrexed disodium hemipenta hydrate).
Each ml of concentrate for solution for infusion contains 25 mg of pemetrexed (as pemetrexed
disodium hemipenta hydrate).
Each vial of 4 ml contains 100 mg of pemetrexed (as pemetrexed disodium hemipenta hydrate).
Each vial of 20 ml contains 500 mg of pemetrexed (as pemetrexed disodium
hemipenta hydrate).
Each vial of 40 ml contains 1000 mg of pemetrexed (as pemetrexed disodium
hemipenta hydrate).
The other ingredients are sodium thiosulfate pentahydrate (E539), propylene glycol (E1520), hydrochloric
acid (for pH adjustment), sodium hydroxide (E524) (for pH adjustment), water for
injections.

Description of the appearance of Pemetrexed Sandoz BV and contents of the pack
Pemetrexed Sandoz BV is a concentrate for solution for infusion. It is a clear,
colourless to yellow or yellowish-green solution. Solution practically free from particles.
Pemetrexed Sandoz BV is packaged in a type I glass vial, with a bromobutyl rubber stopper and an aluminium
tear-off cap with a plastic blue tamper-evident seal.
Each vial contains 4 ml, 20 ml or 40 ml of concentrate for solution for infusion.
Each pack contains 1 vial (with or without coating).

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
Sandoz BV
Veluwezoom 22
1327 AH Almere
The Netherlands

Local Representative for Italy: Sandoz S.p.A., L.go U. Boccioni 1, 21040 Origgio (VA), Italy

Manufacturer
Ebewe Pharma Ges.m.b.H. Nfg.KG
Mondseestrasse 11,
4866 Unterach am Attersee,
Austria

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
Austria Pemetrexed Sandoz 25 mg/ml – Concentrate for the preparation of an
infusion solution
Belgium Pemetrexed Sandoz 25 mg/ml concentrate for solution for infusion
Bulgaria Пеметрексед Сандоз 25 mg/ml концентрат за инфузионен разтвор
Denmark Pemetrexed Hexal
Finland Pemetrexed Hexal 25 mg/ml
Infusion concentrate, for solution
France Pemetrexed GNR 25 mg/ml, solution à
diluer pour perfusion
Germany Pemetrexed HEXAL 25 mg/ml Concentrate for the preparation of an infusion solution
Greece Pemetrexed/EBEWE 25mg/ml πυκνό διάλυμα για παρασκευή διαλύματος
προς έγχυση
Ireland Pemetrexed Rowex 25 mg/ml concentrate for solution for Infusion
Iceland Pemetrexed Hexal 25 mg/ml Concentrate for infusion fluid, solution
Italy Pemetrexed Sandoz BV
Lithuania Pemetrexed Ebewe 25mg/ml koncentratas infuziniam tirpalui
Norway Pemetrexed Hexal
Netherlands Pemetrexed Sandoz 25 mg/ml, concentrate for solution for infusion
Poland Pemetrexed Sandoz
Portugal Pemetrexed Sandoz
Slovenia Pemetreksed Sandoz 25 mg/ml koncentrat za raztopino za infundiranje
Spain Pemetrexed Ebewe 25mg/ml concentrado para solución para perfusión
Sweden Pemetrexed Hexal 25 mg/ml Concentrate for infusion fluid, solution
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The following information is intended exclusively for healthcare professionals:
Special precautions for use and handling

Pemetrexed solutions are for single use. Any unused medicinal product and waste materials derived
from it must be disposed of in accordance with local regulations for cytotoxic agents

• 1. Use aseptic techniques when diluting pemetrexed for intravenous infusion.
• 2. Calculate the dose and the number of vials of Pemetrexed Sandoz BV needed. Each vial contains an excess of pemetrexed concentrate to facilitate dispensing the amount indicated on the label.
• 3. The appropriate volume of pemetrexed concentrate must be further diluted to 100 ml with a solution (without preservatives) for injections of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) and administered by intravenous infusion over 10 minutes.
• 4. Infusion solutions of pemetrexed prepared as above are compatible with polyolefin-coated infusion bags and administration sets.
• 5. Before administration, parenteral medicines should be visually inspected for the presence of particles and colour changes. Do not administer if particles are observed.

Precautions for preparation and administration:As with other potentially toxic anti-cancer 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, wash thoroughly with water.
Pemetrexed is not 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 procedures as for other non-vesicant agents.
Monitoring
Patients receiving pemetrexed should undergo a complete blood count, including white blood cell count with
differential (WBC) and platelet count, before each administration. Biochemical hematological tests should be
performed before each chemotherapy administration to assess renal and hepatic function. Before starting a
chemotherapy cycle, patients must have the following values: absolute neutrophil count (ANC) must be  1,500
cells/mm3 and platelets must be  100,000 cells/mm3. Creatinine clearance must be  45 ml/min.
Total bilirubin must be  1.5 times the upper limit of the normal value. Alkaline phosphatase (AP), aspartate
aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) must be  3 times the upper
limit of the normal value. Alkaline phosphatase, AST and ALT  5 times the upper limit of the normal value are
acceptable if the liver is the site of metastases.
Dose adjustments
Dose adjustments at the start of a subsequent cycle must be made based on the hematological count at the nadir
or the maximum degree of non-hematological toxicity observed during the previous cycle of therapy. Treatment
may be delayed to allow a sufficient period of recovery. Once patients have recovered, they should be
retreated according to the guidelines indicated in Tables 1, 2 and 3 which are applicable for Pemetrexed Sandoz
BV used as a single agent or in combination with cisplatin.

Bleeding ≥ Grade 2 according to the National Cancer Institute Common Toxicity Criteria
(CTC) (v2.0; NCI 1998)
If patients develop non-hematological toxicity  Grade 3 (excluding neurotoxicity), Pemetrexed
Sandoz BV should be suspended until the value returns to a value less than or equal to that the
patient had before therapy. Treatment should be restarted according to the guidelines
indicated in Table 2.

National Cancer Institute Common Toxicity Criteria (CTC v2.0; NCI 1998)
Excluding neurotoxicity
In case of neurotoxicity, the recommended dose adjustment for Pemetrexed Sandoz BV and
cisplatin is described in Table 3. Patients should discontinue therapy if neurotoxicity of Grade 3 or 4 is observed.
National Cancer Institute Common Toxicity Criteria (CTC v2.0; NCI 1998)
Treatment with Pemetrexed Sandoz BV should be discontinued if a patient develops any
hematological or non-hematological toxicity of Grade 3 or 4 after 2 dose reductions or immediately
if neurotoxicity of Grade 3 or 4 is observed.

Elderly
In clinical studies, there was no evidence that patients aged 65 years or older were at increased risk for
adverse reactions compared to younger patients under 65 years of age. No dose reductions are necessary
beyond those recommended for all patients.

Patients with renal impairment(Standard Cockcroft and Gault formula or Method for calculating
glomerular filtration with Tc99m-DPTA)
Pemetrexed is primarily eliminated unchanged by renal excretion. In clinical studies,
patients with creatinine clearance  45 ml/min did not require dose adjustments
beyond those recommended for all patients. There are insufficient data on the use of pemetrexed in
patients with creatinine clearance less than 45 ml/min; therefore the use of pemetrexed is
not recommended (see section 4.4).

Patients with hepatic impairment
No relationships have been identified between AST (SGOT), ALT (SGPT) or total bilirubin and the
pharmacokinetics of pemetrexed. However, patients with hepatic impairment, such as those with bilirubin > 1.5
times the upper limit of the normal value and/or with aminotransferases > 3.0 times the upper limit of the
normal value (in the absence of hepatic metastases) or > 5.0 times the upper limit of the normal value (in the
presence of hepatic metastases) have not been specifically studied.