Package Leaflet: Information for the Patient

Isovorin 5 mg Tablets

Levofolinic Acid

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

If you have any questions, ask your doctor, pharmacist or nurse.

• 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 harm them.

• If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1.What Isovorin is and what it is used for

2.What you need to know before you start taking Isovorin

3.How to take Isovorin

4.Possible side effects

5Storage of Isovorin

6.Contents of the pack and additional information

Isovorin contains levofolic acid in the form of calcium levofolinate. Levofolic acid is the active form of folic acid. Levofolic acid acts in processes that involve folate deficiency and as an antidote for folic acid antagonists (it belongs to the group of medications known as detoxifying agents for the treatment of tumors).

This medication is used in the following cases:

-Treatment of disorders that involve folate deficiency (megaloblastic anemias, alcoholism, malabsorption syndrome, nutritional deficiency in children and/or the elderly).

-Antidote for folic acid antagonists such as Methotrexate.

Do not use Isovorin

• If you are allergic to levofolic acid or any of the other components of this medication (listed in section 6).
• If you have anemia (a disorder characterized by a decrease in the number of red blood cells and/or hemoglobin in the blood), whether it is pernicious or other megaloblastic anemias secondary to a lack of vitamin B12.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Isovorin tablets.

Your doctor will inform you about the benefits and risks of treatment with Isovorin tablets, as well as the symptoms that may indicate possible toxicity due to the medication.

If you are in any of the following cases, consult your doctor before using this medication:

• If you are epileptic and are being treated with phenobarbital, phenytoin, primidone, and succinimides, as there is a risk of an increase in seizure frequency (see section “Other medications and Isovorin”).
• If you are taking folic acid antagonists such as chloramphenicol (an antibiotic).
• If you are being treated with methotrexate or 5-fluorouracil. It is essential to follow the Isovorin dose prescribed by your doctor strictly, as non-compliance may cause excessive toxicity or a lack of efficacy of methotrexate.
• If you have pernicious anemia and other megaloblastic anemias resulting from a deficiency in vitamin B12.
• If you are being treated with cytotoxic drugs that inhibit direct or indirect DNA synthesis, such as hydroxyurea, cytarabine, mercaptopurine, or thioguanine, and have presented microcytosis.

Other medications and Isovorin

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Particularly, inform your doctor if you are using the following medications:

• Folic acid antagonists such as cotrimoxazole, pyrimethamine, or chloramphenicol, as levofolic acid may reduce their efficacy.
• Antiepileptic medications (such as phenobarbital, phenytoin, succinimides, or primidone), as high doses may partially decrease their effect and increase the frequency of seizures (see section “Warnings and precautions”).
• Medications such as methotrexate or 5-fluorouracil. Folinic acid calcium should only be used with methotrexate or 5-fluorouracil under the direct supervision of an experienced doctor in the use of chemotherapeutic agents.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication. There have been no adequate and well-controlled clinical studies in pregnant women or breastfeeding women.

The excretion of folinic acid calcium in breast milk is unknown. Folinic acid calcium may be used during breastfeeding if considered necessary according to therapeutic indications.

No studies on fertility have been conducted with folinic acid calcium.

Driving and operating machinery

This medication has no effect on the ability to drive vehicles or operate machinery.

This medication contains lactose and sodium

This medication contains lactose. If your doctor has indicated that you have a certain sugar intolerance, consult with them before taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per dose unit; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The tablet can be taken on an empty stomach or after meals.

Folate deficiency treatment

The recommended dose is 2.5 mg to 5 mg per day (usually one tablet per day), administered orally.

Your doctor will indicate the dose and duration of treatment taking into account your situation.

Antidote for folic acid antagonists

High-dose Methotrexate rescue: It will be done with doses of 7.5 mg (approximately 5 mg/m2) of levofolinic acid administered intravenously, intramuscularly or orally if tablets are used, every 6 hours for 72 hours and with a total of 10 doses. Treatment will start 24 hours after the start of methotrexate perfusion. The dose will be individual for each patient and may be modified by your doctor depending on the severity of the case and the patient's response.

Methotrexate overdose: Rescue should be started as soon as possible after accidental overdose and within 24 hours after methotrexate administration when there is a delay in its elimination. Levofolinic acid doses of 5 mg/m2will be administered intravenously, intramuscularly or orally, every 6 hours, until the methotrexate level in plasma is less than 0.5 µmol/l.

Trimetrexate, trimethoprim and pyrimethamine:

•Trimethoprim toxicity: After stopping trimethoprim, levofolinic calcium should be administered at a dose of 1.5 to 5 mg per day until a normal blood count is recovered.

•Pyrimethamine toxicity: In case of administration of high doses or prolonged treatment with low doses of pyrimethamine, levofolinic calcium should be administered simultaneously at a dose of 2.5 to 25 mg, based on peripheral blood counts.

•Trimetrexate toxicity:

• Prevention: Levofolinic calcium should be administered daily during trimetrexate treatment and for 72 hours after the last dose of trimetrexate.

Levofolinic calcium can be administered orally with four doses of 20 mg/m2administered at equal time intervals. Levofolinic calcium daily doses should be adjusted depending on the hematological toxicity of trimetrexate.

• Overdose (possibly with trimetrexate doses greater than 90 mg/m2without concomitant administration of folinic acid): After stopping trimetrexate, 20 mg/m2 levofolinic calcium should be administered every 6 hours for 3 days.

If you take more Isovorin than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Isovorin

Do not take a dose to compensate for the missed doses.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Rare adverse effects (may affect up to 1 in 1,000 people) include:

• Seizures and/or syncope.
• Depression.
• Agitation.
• Digestive problems.
• Difficulty sleeping (insomnia).

Very rare adverse effects (may affect up to 1 in 10,000 people) include:

• Severe allergic reaction: you may experience a sudden rash with itching (urticaria), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and may feel like you are going to faint. This is a serious side effect. You may need urgent medical attention.

Adverse effects of unknown frequency (cannot be estimated from available data) include:

• Fever.

Reporting Adverse Effects:

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaram.es. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

This medication does not require special storage conditions. Store below 25°C and protected from light.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Isovorin

• The active ingredient is folic acid. Each tablet contains 5 mg of levofolic acid in the form of calcium levofolinate.
• The other components (excipients) are lactose, microcrystalline cellulose, sodium glycolate potato starch, silicon dioxide, and magnesium stearate.

Appearance of Isovorin and content of the packaging

Oval, biconvex tablets, white in color, marked with “L L” on the lower face and “I 7” on the upper face, packaged in a blister.

Package with 30 tablets.

Marketing Authorization Holder:

Pfizer, S.L.

Avenida de Europa, 20-B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Responsible for manufacturing

Farmasierra Manufacturing, S.L.

Carretera de Irún, Km. 26,200

28700 San Sebastián de los Reyes (Madrid)

Last review date of this leaflet: October 2023

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/