Prefolic

Package leaflet: Information for the patient

Prefolic 15 mg gastro-resistant tablets

Calcium N5-methyltetrahydrofolate
Read this leaflet carefully before taking 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 pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Prefolic is and what it is used for

Prefolic is a medicine used:

• For the treatment of folate deficiency due to:
• increased demand for folates by the body
• reduced ability of the body to absorb folates
• insufficient dietary intake of folate-containing foods
• Prefolic is also used to increase folate intake in cases of administration of excessive doses of medicines that reduce folic acid in the body (folic acid antagonists);
• To counteract the side effects induced by the intake of medicines containing aminopterin and methotrexate.

2. What you should know before taking Prefolic

Do not use Prefolic

• if you are allergic to calcium N5-methyltetrahydrofolate or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before taking Prefolic.
If you suffer from pernicious anemia (a blood disorder caused by impaired absorption of vitamin B12), it is advisable to also take vitamin B12 together with Prefolic to prevent possible neurological complications of the disease caused by deficiency of vitamin B12.
Other medicines and Prefolic
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are being treated with medicines for epilepsy (anticonvulsants), as taking Prefolic at the same time may increase the frequency of epileptic seizures.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
As it is a vitamin, Prefolic has no adverse effects on the mother or fetus.
Driving and using machines
This medicine does not impair the ability to drive or operate machinery.
Prefolic contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Prefolic contains sodium
Prefolic contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Prefolic

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Recommended dose:

• In the treatment of folate deficiency due to increased demand, reduced absorption, or a diet poor in this vitamin: One 15 mg tablet daily or on alternate days, according to your doctor's prescription. Treatment with this medicine should continue until symptoms of deficiency have completely resolved and blood parameters (hematological parameters) have returned to normal (repletion of endogenous stores).
• To increase folate intake when administering excessive doses of folic acid antagonists (e.g. high-dose methotrexate): One 15 mg tablet every 6–8 hours. Therapy should continue for several days, depending on hematological parameters (blood tests).

Method of administration:
The tablets are gastro-resistant, meaning they release the active substance in the first part of the intestine.
Do not chew the tablets; swallow them whole, preferably in the morning.

If you take more Prefolic than you should
In case of accidental ingestion or overdose of Prefolic, contact your doctor immediately or go to the nearest hospital.

If you forget to take Prefolic
Continue your treatment as prescribed with the next dose. Do not take a double dose to make up for the forgotten dose.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects that may occur after taking this medicine include:

• fever
• urticaria (skin reaction, sometimes with itching)
• hypotension (low blood pressure)
• tachycardia (increased heart rate)
• bronchospasm (breathing difficulty)
• anaphylactic shock (severe allergic reaction)

The frequency of these side effects is not known.
Following the instructions provided in this leaflet reduces the risk of side effects.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via 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 Prefolic

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated on the pack.
Store the tablets protected from light and at a temperature not exceeding 30°C.
Do not dispose of any medicine via 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 Prefolic contains

• The active substance is: Calcium N5-methyltetrahydrofolate pentahydrate.
• The other ingredients are: maize starch, lactose, magnesium stearate, polyethylene glycol 6000, polymethacrylates, polysorbate 80, simethicone, sodium hydroxide, talc.

Description of the appearance of Prefolic and the contents of the pack
Prefolic is available as gastro-resistant tablets. The pack contains 30 tablets.

Marketing Authorization Holder
ZAMBON Italia s.r.l. – Via Lillo del Duca 10 – 20091 Bresso (MI)

Manufacturer
Avara Liscate Pharmaceutical Services S.p.A. – Via Fosse Ardeatine 2, Liscate (MI)
ZAMBON S.p.A. – Via della Chimica 9, Vicenza

Patient Information Leaflet

Prefolic 15 mg/3 ml powder and solvent for injectable solution

Prefolic 50 mg/3 ml powder and solvent for injectable solution
Calcium N5-methyltetrahydrofolate
Please read this leaflet carefully before using 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 pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Prefolic is and what it is used for

Prefolic is a medicine used:

• For the treatment of folate deficiency due to:
  • increased demand for folates by the body
  • reduced ability of the body to absorb folates
  • insufficient dietary intake of folate-containing foods
• To increase folate intake in cases of excessive administration of medicines that reduce folic acid levels in the body (folic acid antagonists);
• To counteract the side effects induced by the intake of medicines containing aminopterin and methotrexate.

2. What you need to know before using Prefolic

Do not use Prefolic

• if you are allergic to calcium N5-methyltetrahydrofolate or to any of the other ingredients of this medicine (listed in section 6).
• if the patient is a newborn (≤28 days of age). Prefolic (or other solutions containing calcium) must not be administered simultaneously with ceftriaxone (an antibiotic), even when using separate infusion lines. There is a fatal risk of particle formation in the newborn's bloodstream.

Warnings and precautions
Talk to your doctor or pharmacist before using Prefolic.
If you suffer from pernicious anemia (a blood disorder caused by impaired vitamin B12 absorption), it is advisable to also take vitamin B12 together with Prefolic to prevent potential neurological complications of the disease caused by vitamin B12 deficiency.
If this medicine is administered by slow infusion (slow intravenous infusion), avoid exposing the solution to air and avoid concomitant administration of bicarbonates.

Other medicines and Prefolic
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are being treated with medicines for epilepsy (anticonvulsants), as concomitant use of Prefolic may increase the frequency of epileptic seizures.
Prefolic interacts with ceftriaxone (an antibiotic) due to the risk of particle formation.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Since this is a vitamin, Prefolic has no adverse effects on the mother or fetus.

Driving and using machines
This medicine does not impair the ability to drive or operate machinery.

Prefolic contains methyl p-hydroxybenzoate (parabens)
May cause allergic reactions (including delayed reactions) and, exceptionally, bronchospasm.

Prefolic contains sodium
Prefolic contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially 'sodium-free'.

3. How to use Prefolic

Use this medicine exactly as prescribed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Prefolic can be administered by intramuscular or intravenous route.
The recommended dose is :

• In the treatment of folate deficiency due to increased requirements, reduced absorption, or a diet poor in this vitamin: One vial daily or on alternate days, as prescribed by your doctor, administered intramuscularly or intravenously. Treatment with this medicine should continue until complete resolution of deficiency symptoms and restoration of normal blood parameters (replenishment of endogenous folate stores).
• To increase folate supply in cases of excessive administration of folic acid antagonists (e.g. high-dose methotrexate): 50–100 mg intravenously every 3–8 hours. Therapy should continue for several days, depending on hematological parameters (blood tests).

Method of administration:
If the medicine is administered intravenously, the injection should be given slowly.
Instructions for use
Prefolic will be prepared by a doctor, pharmacist, or nurse and must not be mixed or administered simultaneously with injections containing ceftriaxone or bicarbonate.
Opening the vial: Position the vial as shown in figure 1 and apply pressure with your thumb placed over the coloured spot as indicated in figure 2.

Preparation of the reconstituted solution:

1. Open the vial as described above
2. Using a sterile syringe, withdraw the solvent from its vial
3. Lift the central portion of the aluminum cap covering the vial
4. Inject the solvent into the vial containing the powder by piercing the rubber stopper
5. Shake the reconstituted solution and administer as prescribed by the doctor (intramuscularly or
   intravenously)
   If you use more Prefolic than you should
   In case of accidental ingestion or administration of an excessive dose of Prefolic, contact your doctor immediately or go to the nearest hospital.
   If you forget to take Prefolic
   Continue your treatment as prescribed. Do not take a double dose to make up for the missed dose.
   If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The side effects that may occur after taking this medicine include:

• fever
• urticaria (skin reaction, sometimes with itching)
• hypotension (low blood pressure)
• tachycardia (increased heart rate)
• bronchospasm (breathing difficulty)
• anaphylactic shock (severe allergic reaction)
• kidney problems caused by calcium-ceftriaxone deposits. This may cause pain when urinating, or a reduced amount of urine produced (anuria), nausea and vomiting.

The frequency of these side effects is not known.
Following the instructions in this leaflet reduces the risk of side effects.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You may also report side effects directly via 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 Prefolic

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated on the package.
Keep the vials protected from light.
Do not dispose of medicines via 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 Prefolic contains

• The active substance is: Calcium N5-methyltetrahydrofolate pentahydrate.
• The other components are: citric acid, glutathione, mannitol, methyl p-hydroxybenzoate, sodium hydroxide. The solvent vial contains: water for injections.

Description of the appearance of Prefolic and contents of the pack
Prefolic is available as a powder and solvent for injectable solution.
Prefolic 15 mg/3 ml powder and solvent for solution for injection
Pack containing 5 vials of powder and 5 solvent vials.
Prefolic 50 mg/3 ml powder and solvent for solution for injection
Pack containing 6 vials of powder and 6 solvent vials.

Marketing Authorization Holder
Zambon Italia s.r.l. – Via Lillo del Duca 10 – 20091 Bresso (MI)

Manufacturer
Avara Liscate Pharmaceutical Services S.p.A. – Via Fosse Ardeatine 2, Liscate (MI)
Zambon S.p.A. – Via della Chimica 9, Vicenza