Leucovorin

Leucovorin is a substance that replenishes the deficiency of folic acid.

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Indications Leucovorina

It is used in the following conditions:

• poisoning with drugs that are vitamin B9 antagonists (such as methotrexate with pyrimethamine and trimethoprim);
• pernicious anemia associated with vitamin B9 deficiency;
• to prevent the development of toxic effects in the case of using large doses of methotrexate;
• during combination treatment of colorectal oncology (combination of fluorouracil with leucovorin).

Release form

The substance is released in the form of a lyophilisate, from which liquids are made for intramuscular or intravenous use; inside glass vials with a capacity of 20 ml. The box contains 1 or 10 such vials. Liquid for intravenous injections can also be produced in vials with a capacity of 45 or 80 ml (1 piece inside the pack).

In addition, it is available in tablet form (volume 15 mg), 10 or 30 pieces per box.

May be contained in 25 mg (or 2 ml) ampoules, 5 pieces per pack.

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Pharmacodynamics

Leucovorin is a reduced form of vitamin B9 (a derivative of tetrafolic acid). In medicine, it is used as an antidote to drugs that are antagonists of vitamin B9 and interfere with the synthesis of tetrahydrofolate from it, which is considered the main cofactor in the processes of nucleic acid biosynthesis. In this case, the binding of the latter is blocked and the process of cell division is destroyed.

Unlike vitamin B9, folinate Ca does not require the process of conversion into tetrahydrofolate, so when using it, the disrupted biosynthesis of protein components and DNA with RNA can be restored. But such an effect affects only healthy cells.

The drug replenishes the deficiency of vitamin B9 in the body and at the same time potentiates the effect of fluorouracil, which has antitumor properties. The interaction of these drugs leads to the formation of a stable complex, including thymidylate synthetase, which demonstrates a retarding effect on DNA binding.

The medicinal effect after an intramuscular injection develops after 10-20 minutes, and after an intravenous injection - after 5 minutes. This effect lasts for 3-6 hours (with any form of application).

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Pharmacokinetics

After an intramuscular injection of Leucovorin, drug-induced effects are noted after 2 hours; after an intravenous injection – after 10 minutes.

Accumulation occurs mainly within the liver; the substance can penetrate the BBB. Metabolic processes occur within the intestines with the liver, resulting in the formation of a therapeutically active component – 5-methyltetrahydrofolate.

Excretion of 80-90% of the drug dose occurs with urine, and another 5-8% is excreted with feces.

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Dosing and administration

The medication can be taken orally, or administered intramuscularly or intravenously. Various therapeutic regimens are used; when selecting a dosage, the doctor must follow the treatment regimens prescribed for different diseases.

^{When combined with fluorouracil, the drug is administered at a low rate intravenously (0.2 g/ m2} dose ) or through a drip followed by intravenous administration of fluorouracil in a dose of 0.37 g/m2 ⁾. The drugs are used within a 5-day period, with 4-5-week intervals between repeated cycles.

To prevent the development of the toxic effects of trimethoprim, Leucovorin is used in a dose of 3-10 mg per day until hematological values are stabilized.

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Use Leucovorina during pregnancy

B9 vitamin is contained in the composition of combined vitamin preparations prescribed during pregnancy. But special tests with the study of the effect of Leucovorin on such women have not been performed. Therefore, if there is a need to take the drug, the doctor should decide on its appointment.

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Contraindications

Main contraindications:

• severe drug intolerance;
• pernicious anemia with vitamin B12 deficiency.

Caution is necessary when using the medication in people with epilepsy, alcoholism or chronic renal failure, and also when prescribing to children.

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Side effects Leucovorina

The introduction of the drug may provoke local signs of allergy, sleep disorders, dyspeptic symptoms, a feeling of excitement and a state of depression.

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Interactions with other drugs

The drug weakens the activity of vitamin B9 antagonist drugs and also reduces the anticonvulsant effect of phenobarbital and phenytoin with primidone.

The drug is capable of potentiating the toxic and medicinal properties of fluorouracil, which must be taken into account when selecting the dosage of the latter.

It is prohibited to combine Leucovorin with infusion fluids containing bicarbonate.

Mixing the drug and droperidol in the same syringe will result in a precipitate.

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Storage conditions

Leucovorin must be stored in a dry place at a maximum temperature of 25°C.

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Shelf life

Leucovorin can be used within a 36-month period from the date of release of the pharmaceutical product.

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Analogues

The analogs of the drug are Leucovorin calcium, Calcium folinate, Leucovorin-Teva, and also Leucovorin-LENS with Sanficinat and Calciumfolinate-Ebeve.