ISOVORIN 5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Isovorin 5 mg Tablets

Levofolinic Acid

Read this package leaflet carefully before you start using this medicine, as it contains important information for you.Keep this package leaflet, you may need to read it again.

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

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

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

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

Contents of the Package Leaflet

1. What Isovorin is and what it is used for
2. What you need to know before you take Isovorin
3. How to take Isovorin
4. Possible side effects

5 Conservation of Isovorin

1. Contents of the pack and further information

1. What Isovorin is and what it is used for

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

This medicine is used in the following cases:

• Treatment of disorders that involve folate deficiency (megaloblastic anemia, alcoholism, malabsorption syndrome, nutritional deficiency in children and/or the elderly).
• Antidote to folic acid antagonists such as Methotrexate.

2. What you need to know before you take Isovorin

Do not take Isovorin

• if you are allergic to levofolinic acid or any of the other ingredients of this medicine (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 pernicious or other megaloblastic anemia secondary to vitamin B12 deficiency.

Warnings and Precautions

Talk to your doctor, pharmacist, or nurse before taking 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 medicine.

If you are in any of the following situations, consult your doctor before taking this medicine:

• If you are epileptic and are being treated with phenobarbital, phenytoin, primidone, and succinimides, as there is a risk of increased frequency of seizures (see section "Other Medicines and Isovorin").
• If you are taking folic acid antagonist medicines such as chloramphenicol (an antibiotic).
• If you are being treated with methotrexate or 5-fluorouracil. It is essential that you strictly follow the dose of Isovorin prescribed by your doctor, as non-compliance may cause excessive toxicity or lack of efficacy of methotrexate.
• If you have pernicious anemia and other megaloblastic anemia resulting from vitamin B12 deficiency.
• If you are being treated with cytotoxic medicines that directly or indirectly inhibit DNA synthesis, such as hydroxyurea, cytarabine, mercaptopurine, or thioguanine, and have presented microcytosis.

Other Medicines and Isovorin

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

In particular, tell your doctor if you are using the following medicines:

• Folic acid antagonist medicines such as cotrimoxazole, pyrimethamine, or chloramphenicol, as levofolinic acid may reduce their efficacy.
• Antiepileptic medicines (such as phenobarbital, phenytoin, succinimides, or primidone), as high doses may partially reduce their effect and increase the frequency of seizures (see section "Warnings and Precautions").
• Medicines such as methotrexate or 5-fluorouracil. Calcium folinate should only be used with methotrexate or 5-fluorouracil under the direct supervision of an experienced doctor in the use of cancer chemotherapeutic agents.

Pregnancy, Breastfeeding, and Fertility

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

It is not known whether calcium folinate is excreted in breast milk. Levofolinic acid calcium can be used during breastfeeding if considered necessary according to therapeutic indications.

No fertility studies have been conducted with calcium folinate.

Driving and Using Machines

This medicine has no effects on the ability to drive vehicles or use machines.

This Medicine Contains Lactose and Sodium

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to Take Isovorin

Follow exactly the administration instructions of this medicine 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.

Treatment of Folate Deficiencies

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

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

Antidote to Folic Acid Antagonists

Rescue of high doses of Methotrexate: 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 infusion. The dose will be individual for each patient and may be modified by your doctor depending on the severity of the condition and the patient's response.

Overdose of Methotrexate: 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/m2 will 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, a dose of 1.5 to 5 mg of calcium levofolinate should be administered daily until a normal blood count is recovered.

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

• Trimetrexate toxicity:
  • Prevention: Calcium levofolinate should be administered every day during treatment with trimetrexate and for 72 hours after the last dose of trimetrexate.

Calcium levofolinate can be administered orally with four doses of 20 mg/m2 administered at equal intervals. The daily doses of calcium levofolinate should be adjusted depending on the hematological toxicity of trimetrexate.

• Overdose (possibly with trimetrexate doses higher than 90 mg/m2 without concomitant administration of calcium folinate): After stopping trimetrexate, 20 mg/m2 of calcium levofolinate 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 Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If You Forget to Take Isovorin

Do not take a dose to make up for forgotten doses.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

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

Very rare side 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.

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

• Fever.

Reporting of Side Effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this package leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Isovorin

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

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

Do not use this medicine after the expiry date which is stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the Pack and Further Information

Composition of Isovorin

• The active substance is folinic acid. Each tablet contains 5 mg of levofolinic acid in the form of calcium levofolinate.
• The other ingredients (excipients) are lactose, microcrystalline cellulose, sodium starch glycolate, silicon dioxide, and magnesium stearate.

Appearance of Isovorin and Contents of the Pack

Oval, biconvex tablets, white, marked with "L L" on the lower face and "I 7" on the upper face, packaged in blisters.

Pack containing 30 tablets.

Marketing Authorization Holder:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Manufacturer

Farmasierra Manufacturing, S.L.

Carretera de Irún, Km. 26,200

28700 San Sebastián de los Reyes (Madrid)

Date of Last Revision of this Package Leaflet: October 2023

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/