Isovorin 5 mg tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Isovorin 5 mg tablets

Leucovorin acid

Read the entire leaflet carefully before you start using 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, consult your doctor, pharmacist or nurse.

• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.

• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if these are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Isovorin is and what it is used for
2. What you need to know before using Isovorin
3. How to use Isovorin
4. Possible side effects
5. Storage of Isovorin
6. Contents of the pack and other 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 conditions associated with folate deficiency and as an antidote to folic acid antagonists (it belongs to the group of medicines known as detoxifying agents for tumor treatment).

This medicine is used in the following cases:

• Treatment of disorders associated with folate deficiency (megaloblastic anemias, 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 using Isovorin

Do not use Isovorin

• if you are allergic to levofolinic acid or any of the other components of this medicine (listed in section 6).
• if you have anaemia (a disorder characterized by a reduction in the number of red blood cells and/or haemoglobin in the blood), either pernicious anaemia or other megaloblastic anaemias secondary to vitamin B12 deficiency.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before starting to take 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 drug-related toxicity.

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

• If you have epilepsy and are being treated with phenobarbital, phenytoin, primidone, or succinimides, as there is a risk of increased seizure frequency (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 important that you strictly follow the Isovorin dosage prescribed by your doctor, as failure to do so may result in excessive toxicity or reduced efficacy of methotrexate.
• If you have pernicious anaemia or other megaloblastic anaemias resulting from vitamin B12 deficiency.
• If you are being treated with cytotoxic drugs that directly or indirectly inhibit DNA synthesis, such as hydroxycarbamide, cytarabine, mercaptopurine, or thioguanine, and you have developed microcytosis.

Other medicines and Isovorin

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

In particular, inform your doctor if you are taking the following medicines:

• Folic acid antagonist medicines such as cotrimoxazole, pyrimethamine, or chloramphenicol, as levofolinic acid may reduce their effectiveness.
• 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 a physician experienced in the use of cytotoxic anticancer agents.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Adequate and well-controlled clinical studies have not been conducted in pregnant or breastfeeding women.

It is unknown whether calcium folinate is excreted in human breast milk. Calcium leucovorin may be used during breastfeeding if considered necessary according to therapeutic indications.

Fertility studies have not been conducted with calcium folinate.

Driving and using machines

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

This medicine contains lactose and sodium

This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, consult him before taking this medicine.

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

3. How to use Isovorin

Follow exactly the administration instructions for this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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

Folate deficiency treatment

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

Your doctor will determine the dose and duration of treatment according to your individual condition.

Antidote for folic acid antagonists

Rescue after high-dose Methotrexate: Rescue will be performed with doses of 7.5 mg (approximately 5 mg/m²) of levoleucovorin administered intravenously, intramuscularly, or orally (if tablets are used), every 6 hours for 72 hours, for a total of 10 doses. Treatment should begin 24 hours after the start of methotrexate infusion. The dose will be individualized for each patient and may be adjusted by your doctor depending on the severity of the condition and the patient's response.

Methotrexate overdose: Rescue should be initiated as soon as possible after the overdose and within 24 hours after methotrexate administration when delayed elimination is present. Levoleucovorin 5 mg/m² should be administered intravenously, intramuscularly, or orally every 6 hours until the plasma methotrexate level falls below 0.5 µmol/L.

Trimetrexate, trimethoprim, and pyrimethamine:

• Trimethoprim toxicity: After discontinuation of trimethoprim, a daily dose of 1.5 to 5 mg of calcium levofolinate should be administered until a normal blood count is restored.

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

• Trimetrexate toxicity:

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

Calcium levofolinate may be administered orally in four doses of 20 mg/m² given at equal time intervals. Daily doses of calcium levofolinate should be adjusted according to the hematological toxicity of trimetrexate.

• Overdose (possibly with trimetrexate doses exceeding 90 mg/m² without concomitant calcium folinate administration): after discontinuation of trimetrexate, 20 mg/m² of calcium levofolinate should be administered every 6 hours for 3 days.

If you use more Isovorin than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to use Isovorin

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

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

• Seizures and/or fainting.
• 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 you may feel you are about to faint. This is a serious side effect. You may require urgent medical attention.

Adverse effects with frequency not known (cannot be estimated from available data) include:

• Fever.

Reporting of adverse effects:

If you experience any kind of adverse effect, consult your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Isovorin

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

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

Do not use this medicine after the expiry date 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 and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other 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 components (excipients) are lactose, microcrystalline cellulose, sodium starch glycolate from potato, silicon dioxide, and magnesium stearate.

Appearance of Isovorin and contents of the pack

Oval, biconvex, whitish tablets, marked with “L L” on the lower side and “I 7” on the upper side, packed 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 responsible for manufacturing

Farmasierra Manufacturing, S.L.

Carretera de Irún, Km. 26,200

28700 San Sebastián de los Reyes (Madrid)

Date of the most recent revision of this leaflet: October 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/