LEDERFOLIN 7.5 mg Coated tablet

Содержание инструкции

1. LEDERFOLIN 7.5 mg tablets, 2.5 mg granules for oral solution, 25 mg powder for injectable solution for intravenous use
   1. What is Lederfolin and what is it used for
   2. What you need to know before taking Lederfolin
   3. How to take Lederfolin
   4. Possible side effects
   5. How to store Lederfolin
   6. Package Contents and Other Information
2. LEDERFOLIN 100 mg powder for solution for infusion, 175 mg powder for solution for infusion
   1. What is Lederfolin and what is it used for
   2. What you need to know before you are given Lederfolin
   3. How to use Lederfolin
   4. Possible side effects
   5. How to store Lederfolin
   6. Package Contents and Other Information
3. Lederfolin must not be administered by the intrathecal route. It has been reported

LEDERFOLIN 7.5 mg tablets, 2.5 mg granules for oral solution, 25 mg powder for injectable solution for intravenous use

Calcium levofolinate

Read this leaflet carefully before taking 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 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 Lederfolin is and what it is used for
• 2. What you need to know before you take Lederfolin
• 3. How to take Lederfolin
• 4. Possible side effects
• 5. How to store Lederfolin
• 6. Contents of the pack and other information

1. What is Lederfolin and what is it used for

Lederfolin contains the active substance calcium levofolinate, which belongs to a group of medicines
called “detoxifying substances for cytostatic treatments”. Calcium levofolinate is derived
from folic acid and is essential for the synthesis of DNA, an organic substance containing all
the genetic information necessary for the functioning of cells.
Lederfolin is used:

• as an antidote to medicines that prevent the action of folic acid and to combat the side effects of two anticancer medicines: aminopterin and methotrexate.
• to treat anemias due to folate deficiency.

2. What you need to know before taking Lederfolin

Do not take Lederfolin:

• if you are allergic to calcium levofolinate or any of the other ingredients of this medicine (listed in section 6); Lederfolin must not be used in conjunction with ceftriaxone (an antibiotic), even if separate infusion lines are used, as kidney problems caused by calcium-ceftriaxone deposits have occurred.

Warnings and precautions
Talk to your doctor or pharmacist before taking LederfolinUse this medicine in
association with methotrexate (an anticancer medicine) only under the direct supervision of a
doctor experienced in the use of drugs for cancer treatment.
This medicine should not be administered by injection into the lumbar region of the
spine (intrathecal administration). Intrathecal administration of Lederfolin,
performed to counteract an overdose of intrathecal methotrexate, can be fatal.
Talk to your doctor beforetaking Lederfolin if you think that any of the following conditions apply to
you:

• you are undergoing treatment for cancer with any of the following medicines: hydroxycarbamide, cytarabine, mercaptopurine, thioguanine, methotrexate, 5-fluorouracil and similar medicines.;
• you suffer from epilepsy and are taking any of the following medicines: phenobarbital, phenytoin, primidone, succinimide. Combination with Lederfolin may cause an increase in the frequency of epileptic seizures.; Laboratory testsIf your condition requires treatment with Lederfolin in association with methotrexate, your doctor will prescribe frequent blood and urine tests. During therapy, foods (e.g. cheeses, egg yolks, white and red meats, fish; dried fruit, legumes and cereals), drinks (e.g. blueberry juice and yogurt) and medicines that can increase urinary acidity (e.g. those containing bicarbonate) should be avoided.

Other medicines and Lederfolin
Tell your doctor if you are taking, have recently taken or might take any other
medicines.
Tell your doctor if you are being treated with:

• methotrexate (a medicine used to treat some cancers, rheumatic diseases and skin conditions)
• cotrimoxazole, ceftriaxone and chloramphenicol (antibiotics used to treat infections caused by bacteria);
• pyrimethamine (a medicine used for malaria);
• phenobarbital, primidone, phenytoin, succinimide (medicines used to treat epilepsy);
• 5-fluorouracil (an anticancer drug) and similar medicines. 5-fluorouracil must not be combined with Lederfolin in the same injection or intravenous infusion.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding with
breast milk, ask your doctor for advice before taking this medicine.
Pregnancy
Anaemia during pregnancy resulting from increased folate requirements can be improved
or normalised with Lederfolin. No harmful effects from folic acid administered during
pregnancy are known.
Breastfeeding
Calcium levofolinate passes into breast milk, your doctor will prescribe Lederfolin only if
actually necessary.

Driving and using machines
It is not known whether Lederfolin affects the ability to drive vehicles or use machines.

Lederfolin 7.5 mg tablets contains lactose.
If your doctor has diagnosed you with intolerance to certain sugars, contact him/her before taking
this medicine.

Lederfolin 2.5 mg granules for oral solution contains sucrose.
If your doctor has diagnosed you with intolerance to certain sugars, contact him/her before taking
this medicine.

Lederfolin contains sodium
Lederfolin 7.5 mg tablets contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is
essentially ‘sodium-free’.
Lederfolin 25 mg Powder for solution for intravenous injection contains less than 1 mmol
(23 mg) of sodium per vial, i.e. it is essentially ‘sodium-free’.

3. How to take Lederfolin

Take this medicine following exactly the instructions of your doctor. If you have any doubts
consult your doctor.
Lederfolin 7.5 mg tablets and Lederfolin 2.5 mg granules for oral solution are administered
orally. Lederfolin 25 mg powder for injectable solution can be administered into a
vein quickly (intravenously) or slowly (infusion).
In case of intravenous administration, no more than 80 mg of calcium
levofolinate must be injected per minute due to the calcium content of the solution.
Lederfolin must not be administered by the intrathecal route (by injection into the
lumbar region of the spinal cord).

• Use in combination with other antitumor drugs
• Lederfolin can be used in combination with antitumor drugs such as methotrexate to reduce their side effects. The doctor will decide the amount of medicine most suitable for you based on your condition and other medicines you are taking. Treatment of folate deficiency anemiasThe recommended initial dose is 7.5 mg per day orally, for 10-15 days.

If there is improvement, your doctor may decide to halve the dose until the anemia and its symptoms disappear.

If you take more Lederfolin than you should
If you take more Lederfolin than recommended, contact your doctor immediately.
No side effects are known in subjects who have taken much higher doses of calcium levo-
folinate than recommended.
If you have any doubts about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Contact your doctor immediatelyif you experience the following side effects as they may be seriousand your doctor may decide to stop treatment with Lederfolin:

• Stevens-Johnson syndrome, a severe acute hypersensitivity reaction of the skin and mucous membranes in various parts of the body, with the formation of areas of necrosis and peeling. This reaction can sometimes be fatal;
• Toxic Epidermal Necrolysis, a severe acute hypersensitivity reaction, with almost total necrosis of the skin and mucous membranes. This reaction can be fatal;
• Very rare(may affect up to 1 in 10,000 people): severe allergic reaction (anaphylactic shock) - may manifest as hives, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), and you may feel like you are going to faint. This is a serious side effect. You may need urgent medical attention. Uncommon side effects(may affect up to 1 in 100 people):
• fever Rare side effects(may affect up to 1 in 1000 people):
• convulsions (sudden, involuntary, and uncontrolled movements);
• increased frequency of seizures (uncontrolled body movements and loss of consciousness)
• sudden and transient loss of consciousness (syncope)
• depression
• agitation
• problems with the gastrointestinal tract (stomach and intestines)
• insomnia (difficulty falling asleep, staying asleep, or poor sleep quality) Side effects following the use of Lederfolin 25 mg powder for injectable solutiontogether with the anticancer medicine 5-fluorouracil:The following side effects depend on the dosage used of the 5-fluorouracil medicine. Contact your doctor immediatelyif you experience the following side effects as they may be serious(sometimes fatal) and your doctor may decide to stop treatment with Lederfolin:
• severe problems with the stomach and intestines, which may also manifest with inflammation of the mucous membranes and diarrhea;
• Very common(may affect more than 1 in 10 people): reduced production of blood cells such as red blood cells (anemia), white blood cells (increased susceptibility to infections) and platelets (bleeding) by the bone marrow (myelosuppression), including fatal cases;
• Very common(may affect more than 1 in 10 people): inflammation of the mouth and throat (mucositis, stomatitis) (deaths from mucositis have occurred) and
• inflammation of the skin of the lips that manifests with cracks, swelling and small ulcers starting from the corners or edge and extending onto the lips (cheilitis). Very common side effects(may affect more than 1 in 10 people):
• nausea
• vomiting
• severe diarrhea
• dehydration which may be caused by diarrhea, which has led to hospitalization for treatment and even death Common side effects(may affect up to 1 in 10 people):
• redness and swelling of the palms of the hands and soles of the feet that may cause peeling (hand-foot syndrome) Side effects with unknown frequency(frequency cannot be estimated based on available data):
• excessive ammonia in the blood (hyperammonemia) Other side effects:
• low blood pressure (hypotension)
• increased heart rate (tachycardia)
• constriction of the bronchi with difficulty breathing (bronchospasm)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Lederfolin

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 package, blister and
vial after “Exp.”. The expiry date refers to the last day of that month.
Lederfolin 7.5 mg tablets
store at a temperature below 25°C
Keep the blister in the outer packaging to protect the medicine from light.
Lederfolin 2.5 mg granules for oral solution
Do not store at a temperature above 25°C.
Lederfolin 25 mg powder for injectable solution
Do not store at a temperature above 25°C.
The reconstituted solution must be used within 12 hours and stored in a refrigerator (2°C – 8°C).
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Lederfolin contains
The active ingredient is calcium levofolinate hydrate.
Each Lederfolin 7.5 mg tablet contains 9.53 mg of calcium levofolinate hydrate, equivalent to
7.5 mg of levofolinic acid.
The other ingredients are: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate,
anhydrous colloidal silica, magnesium stearate.
Each Lederfolin 2.5 mg oral solution granules sachet contains 3.18 mg of calcium levo-
folinate hydrate, equivalent to 2.5 mg of levofolinic acid.
The other ingredients are: sucrose, strawberry aroma.
Each Lederfolin 25 mg powder for injectable solution vial contains 31.77 mg of calcium
levofolinate hydrate, equivalent to 25 mg of levofolinic acid.
The other ingredients are: mannitol, sodium hydroxide and/or hydrochloric acid (for pH adjustment).

Description of the appearance of Lederfolin and package contents
Lederfolin 7.5 mg tablets are oval-shaped tablets, whitish in color, with
“LL” imprinted on one side and “7.5” on the other side. The tablets are available in blisters in
packages of 10 tablets.
Lederfolin 2.5 mg granules for oral solution are packaged in sachets containing granules of
light yellow color. This medicine is available in packs of 20 and 30 sachets.
Lederfolin 25 mg powder for injectable solution is available in a package containing 1
glass vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina

Manufacturer
Lederfolin 7.5 mg tablets
Farmasierra Manufacturing S.L.(CM)
Carretera de Irun, Km. 26,200
28700 San Sebastían de los Reyes
Madrid (Spain)
Lederfolin 2.5 mg granules for oral solution
Pfizer Consumer Manufacturing Italy S.r.l.
Via Nettunense, 90
Aprilia (LT)
Lederfolin 25 mg powder for injectable solution
Wyeth Lederle S.r.l.
Via F. Gorgone 6
Z.na Ind.le Catania
95030 Catania

The following information is intended exclusively for doctors and healthcare professionals
There is no indication for the use of Lederfolin for pernicious anemia or other megaloblastic anemias resulting from vitamin B12 deficiency.
Dosage and Administration
Lederfolin can be administered orally, intravenously or by infusion. In case of
intravenous administration, no more than 80 mg of calcium levofolinate should be injected per
minute due to the calcium content of the solution.
Use of calcium levofolinate (Lederfolin) within the scope of specific chemotherapeutic
antiblastic protocols with high doses of methotrexate.
Based on the latest findings, to improve the therapeutic index of methotrexate, Lederfolin is
used in a sequential antidote treatment (Lederfolin "rescue"). By adopting
therapeutic schemes that involve the use of methotrexate, at high doses, and Lederfolin, it is
possible to achieve better control of tumor forms, without, at the same time, recording significant
increases in toxicity. The therapeutic protocol provides for the use of Lederfolin by
intravenous route in the first phase corresponding to competition antidotism, orally
(tablets) in the second phase in which the biochemical-metabolic component plays a role.
However, dosage schemes are not yet definitively established.
Since calcium levofolinate is an antagonist of methotrexate, their concomitant
administration can only be carried out when, in individual cases, a specific therapeutic protocol has been defined.
To this end, it is advisable to consult the latest
literature on the subject.
Antidote in case of methotrexate overdose.
Lederfolin should not be administered intrathecally.
Lederfolin (calcium levofolinate), a specific antidote to methotrexate, allows to neutralize the
toxic effects exerted by the antimetabolite on the hematopoietic system and on the mucous membranes of the digestive tract.
In its role as an antidote, Lederfolin is used at different dosages depending on
the effect to be achieved. In cases of accidental overdose, to obtain a competitive effect, Lederfolin is recommended for intravenous infusion (up to 50 mg within 12 hours); to
obtain a biochemical-metabolic effect, Lederfolin is recommended by intravenous route (5-6 mg
every 6 hours for 4 doses) or orally (7.5 mg every 6 hours for 4 doses). In cases of accidental administration,
Lederfolin should be administered in doses equal to or greater than those of
methotrexate within the first hour; the administration of Lederfolin at later times is
less effective.

Lederfolin should not be administered intrathecally. Death has been reported with the
intrathecal administration of calcium levofolinate, following intrathecal overdose of
Methotrexate.
Calcium (levo-) folinate should not be combined with 5-fluorouracil in the same injection or
intravenous infusion.

Reconstitution

• The powder for injectable solution can be reconstituted with 5.3 ml of water for injections;
• For infusion use physiological saline.
• The resulting solution can be stored for a maximum of 12 hours and stored in a refrigerator (2°C-8°C). Instructions for use
• The solution after reconstitution must be clear and yellowish in color. Do not administer if the solution appears cloudy or with particles in suspension;
• The reconstituted solution must be used only once. Any unused portion of the solution must be disposed of in accordance with local laws; IncompatibilitiesIncompatibilities have been reported between injectable forms of calcium levofolinate and injectable forms of droperidol, foscarnet, methotrexate and fluorouracil drugs. The following solutions should not be administered in the same infusion line due to the formation of precipitates:
• Droperidol 1.25 mg/0.5 ml and calcium levofolinate 5 mg/0.5 ml
• Droperidol 2.5 mg/0.5 ml and calcium levofolinate 10 mg/0.5 ml
• Foscarnet 24 mg/ml and calcium levofolinate 20 mg/ml
• 5-fluorouracil should not be mixed with calcium levofolinate in the same injection or intravenous infusion. If the two medicines are administered sequentially through the same infusion line, it is recommended to flush the line with 9 mg/ml (0.9%) sodium chloride injection solution.

LEDERFOLIN 100 mg powder for solution for infusion, 175 mg powder for solution for infusion

Calcium levofolinate

Read this leaflet carefully before you are given this medicine because 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 nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What is Lederfolin and what is it used for

Lederfolin contains the active substance calcium levofolinate, which belongs to a group
of medicines called “detoxifying substances for cytostatic treatments”. Calcium
levofolinate is derived from folic acid and is essential for DNA synthesis, an
organic substance containing all the genetic information necessary for the
functioning of cells.
Lederfolin is used in association with antineoplastic drugs called
fluoropyrimidines for:

• the treatment of colon and rectal cancer when it has spread to different areas of the body (metastases) and when it no longer responds to specific treatments;
• the prevention of the return of colon and rectal cancer after radical surgical removal of the tumor.
• Lederfolin is used for:
• counteracting the side effects of methotrexate and other similar antineoplastic drugs when used at high doses in the treatment of cancers that no longer respond to specific treatments.

2. What you need to know before you are given Lederfolin

Lederfolin must not be given:

• if you are allergic to calcium levofolinate or any of the other ingredients of this medicine (listed in section 6); Lederfolin must not be used in combination with ceftriaxone (an antibiotic), even if using separate infusion lines, as kidney problems caused by calcium-ceftriaxone deposits have occurred. Warnings and precautionsTalk to your doctor or nurse before using this medicine.

This medicine must not be administered by injection into the
lumbar region of the spine (intrathecal administration). Intrathecal
administration of Lederfolin, performed to counteract an overdose of
methotrexate administered intrathecally, can be fatal.
Talk to your doctor beforeyou are given Lederfolin if you think any of the
following conditions apply to you:

• you are undergoing treatment for cancer with any of the following medicines: hydroxycarbamide, cytarabine, mercaptopurine, thioguanine, methotrexate, 5-fluorouracil and similar medicines. You suffer from epilepsy and are taking any of the following medicines: phenobarbital, phenytoin, primidone, succinimide. Combination with Lederfolin may increase the frequency of epileptic seizures. Laboratory testsIf your condition requires treatment with Lederfolin in combination with methotrexate or 5-fluorouracil, your doctor will prescribe frequent blood and urine tests. During therapy, foods (e.g. cheeses, egg yolk, white and red meats, fish; dried fruit, legumes and cereals), drinks (e.g. blueberry juice and yogurt) and medicines that can increase urinary acidity (e.g. those containing bicarbonate) should be avoided.

Other medicines and Lederfolin
Tell your doctor if you are taking, have recently taken or might take
any other medicines.
Tell your doctor if you are being treated with:

• methotrexate (a medicine used to treat some cancers, rheumatic diseases and skin diseases)
• cotrimoxazole, ceftriaxone and chloramphenicol (antibiotics used to treat infections caused by bacteria);
• pyrimethamine (a medicine used for malaria);
• phenobarbital, primidone, phenytoin, succinimide (medicines used for the treatment of epilepsy);
• 5-fluorouracil (an anticancer drug) and similar medicines. 5-fluorouracil must not be combined with Lederfolin in the same injection or intravenous infusion.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you
are breastfeeding, ask your doctor or nurse for advice before you are
given this medicine.
Pregnancy
Anaemia during pregnancy resulting from increased folate requirements can
be improved or normalised with Lederfolin Breastfeeding
Calcium levofolinate passes into breast milk, your doctor will prescribe Lederfolin only
if absolutely necessary.

Driving and using machines
It is not known whether Lederfolin affects the ability to drive or operate machines.

Lederfolin contains sodium
Lederfolin contains less than 1 mmol (23 mg) of sodium per vial, i.e. it is
essentially ‘sodium-free’.

3. How to use Lederfolin

The doctor will decide the amount of medicine to use based on the disease to be
treated and any other medicines you are taking.

If you have been given too much Lederfolin
No side effects are known in subjects who have been given much
higher doses of calcium levofolinate than recommended.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Contact your doctor immediatelyif you experience the following side effects
because they may be seriousand your doctor may decide to stop the
treatment with Lederfolin:

• Stevens-Johnson syndrome, a severe acute hypersensitivity reaction of the skin and mucous membranes in various parts of the body, with the formation of areas of necrosis and shedding. This reaction can sometimes be fatal;
• Toxic Epidermal Necrolysis, a severe acute hypersensitivity reaction, with almost total necrosis of the skin and mucous membranes. This reaction can be fatal; Very rare(may affect up to 1 in 10,000 people): severe allergic reaction (anaphylactic shock) - may manifest as hives, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), and you may feel like you are going to faint. This is a serious side effect. You may need urgent medical attention Uncommon side effects(may affect up to 1 in 100 people):
• fever Rare side effects(may affect up to 1 in 1000 people):
• convulsions (involuntary, sudden and uncontrolled movements);
• increased frequency of seizures (uncontrolled body movements and loss of consciousness) sudden and transient loss of consciousness (syncope)
• depression
• agitation
• problems with the gastrointestinal tract (stomach and intestines)
• insomnia (difficulty falling asleep, staying asleep, poor sleep quality) Side effects following the administration of Lederfolin together with theantitumor medicine 5-fluorouracil.The following side effects depend on the dose of 5-fluorouracil used.

Contact your doctor immediatelyif you experience the following side effects
because they may be serious(sometimes fatal) and your doctor may decide to
stop the treatment with Lederfolin:

• severe problems with the stomach and intestines, which can also manifest with inflammation of the mucous membranes and diarrhea; Very common(may affect more than 1 in 10 people): reduced production of blood cells such as red blood cells (anemia), white blood cells (increased susceptibility to infections) and platelets (bleeding) by the bone marrow (myelosuppression), including fatal cases;
• inflammation of the mouth and throat (mucositis, stomatitis) (deaths from mucositis have occurred) and inflammation of the skin of the lips that manifests with cracks, swelling and small ulcers starting from the corners or edge and extending onto the lips (cheilitis).
• nausea
• vomiting
• severe diarrhea
• dehydration that can be caused by diarrhea, which has led to hospitalization for treatment and even death
• Common side effects(may affect up to 1 in 10 people):
• redness, swelling of the palm of the hands and soles of the feet that can cause peeling (hand-foot syndrome)
• Side effects with unknown frequency(frequency cannot be estimated based on available data):
• excessive ammonia in the blood (hyperammonemia)
• Other side effects:
• low blood pressure (hypotension)
• increased heart rate (tachycardia)
• constriction of the bronchi with difficulty breathing (bronchospasm)

Reporting of side effects
If you experience any side effects, including those not listed in this
leaflet, tell your doctor or nurse. You can also report side effects directly through the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverseReporting side effects
can help provide more information on the safety of
this medicine.

5. How to store Lederfolin

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 the
vial after “Exp.”. The expiry date refers to the last day of that
month.
Do not store at a temperature above 25°C.
The reconstituted solution must be used within 12 hours and stored in a refrigerator
(2°C – 8°C)
Do not dispose of any medicine in wastewater or household waste. Ask your
pharmacist how to eliminate medicines that you no longer use. This will help to
protect the environment.

6. Package Contents and Other Information

What Lederfolin contains
The active ingredient is calcium levofolinate.
Each vial of Lederfolin 100 mg powder for solution for infusion contains
127.08 mg of calcium levofolinate hydrate, equivalent to 100 mg of levofolinic acid.
Each vial of Lederfolin 175 mg powder for solution for infusion contains
222.39 mg of calcium levofolinate hydrate, equivalent to 175 mg of levofolinic acid.
The other ingredients are: mannitol, hydrochloric acid (for pH adjustment),
sodium hydroxide (for pH adjustment).

Description of the appearance of Lederfolin and package contents
Lederfolin 100 mg powder for solution for infusion is available in packs
containing 1 colorless glass vial with a rubber stopper and aluminum crimp cap.
Lederfolin 175 mg powder for solution for infusion is available in packs
containing 1 colorless glass vial with a rubber stopper and aluminum crimp cap.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina

Manufacturer
Wyeth Lederle S.r.l.
Via F. Gorgone 6
Z.na Ind.le Catania
95030 Catania

The following information is intended exclusively for doctors and healthcare
professionals
There is no indication for the use of Lederfolin for pernicious anemia or other megaloblastic anemias resulting from vitamin B12 deficiency.
Dosage
When administered intravenously, no more than 80 mg of calcium levofolinate should be injected per minute due to the calcium content of the solution.
In the treatment of colorectal cancer, in association with fluoropyrimidines, the dosage of calcium levofolinate is determined according to the adopted chemotherapeutic protocols.
The dosages most frequently used in association with 5-fluorouracil are
100 mg/m /day for 5 consecutive days in slow infusion (10 min.) every 4 weeks or
250 mg/m /week for 6 weeks followed by 2 weeks off.
In high-dose methotrexate "rescue", calcium levofolinate is effective in preventing myelosuppression at doses of 100 mg/m for serum methotrexate levels of 10 M. Doses may be proportionally increased for higher blood levels of the antineoplastic agent. Lederfolin should not be administered
by the intrathecal route.

Lederfolin must not be administered by the intrathecal route. It has been reported

death with intrathecal administration of calcium levofolinate, following
intrathecal overdose of Methotrexate.
Calcium (levo-) folinate must not be combined with 5-fluorouracil in the same
injection or intravenous infusion.

Reconstitution:

• Lederfolin 100 mg powder for solution for infusion: the powder can be reconstituted with 10 ml of water for injections.
• Lederfolin 175 mg powder for solution for infusion: the powder can be reconstituted with 15-20 ml of water for injections. Instructions for use:
• The solution after reconstitution must be clear and yellowish in color. Do not administer if the solution appears cloudy or with particles in suspension;
• The reconstituted solution must be used only once. Any unused portion of the solution must be disposed of in accordance with local regulations;
• The obtained solution can be stored for a maximum of 12 hours and stored in a refrigerator (2°C-8° C).

Compatibility
The reconstituted solution is compatible with glucose solution and physiological saline solution.

Incompatibility
Incompatibility has been reported between injectable forms of calcium levofolinate and
injectable forms of the drugs droperidol, foscarnet, methotrexate and fluorouracil.
The following solutions must not be administered in the same infusion line
due to the formation of precipitates:

• Droperidol 1.25 mg/0.5 ml and calcium levofolinate 5 mg/0.5 ml
• Droperidol 2.5 mg/0.5 ml and calcium levofolinate 10 mg/0.5 ml
• Foscarnet 24 mg/ml and calcium levofolinate 20 mg/ml
• Fluorouracil 50 mg/ml and calcium levofolinate. If the two drugs are administered sequentially through the same infusion line, it is recommended to flush the line with sodium chloride injectable solution 9 mg/ml (0.9%).