Leucovorin

Leucovorin is a folic acid deficiency agent.

[1], [2], [3], [4], [5],

Indications Leucovorin

It is used in such conditions:

• poisoning with drugs that are B9 vitamin antagonists (such as methotrexate with pyrimethamine and trimethoprim);
• pernicious anemia associated with B9-vitamin deficiency;
• to prevent the development of a toxic effect in the case of using large portions of methotrexate;
• during the combined treatment of colorectal cancer (combination of fluorouracil and leukovorin).

Release form

The release of a substance is realized in the form of a lyophilisate, from which liquids are prepared for intramuscular or intravenous administration; inside the bottle of glass with a capacity of 20 ml. The box contains 1 or 10 of these bottles. Fluid for IV injection can also be made in bottles 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 inside the box.

May be contained inside ampoules with a capacity of 25 mg (or 2 ml), 5 pieces per pack.

[6],

Pharmacodynamics

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

Unlike B9-vitamin, Ca folinate does not need a process of conversion to tetrahydrofolate, therefore, when it is used, impaired biosynthesis of protein components and DNA with RNA can be restored. But this effect affects only healthy cells.

The drug compensates for the deficiency of B9-vitamin inside the body and, together with this, it 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 drug effect after a / m injection develops after 10–20 minutes, and after intravenous injection, after 5 minutes. This effect lasts within 3-6 hours (in any form of application).

[7], [8]

Pharmacokinetics

After a / m injection of leucovorin, drug indicators are noted after 2 hours; after i / w - after 10 minutes.

Cumulation occurs mainly inside the liver; substance can penetrate the BBB. Metabolic processes take place inside the intestine with the liver, as a result of which a therapeutically active component, 5-methyltetrahydrofolate, is formed.

The excretion of 80-90% of the dose of drugs is carried out with the urine, and another 5-8% is excreted in the feces.

[9], [10], [11], [12], [13], [14],

Dosing and administration

The drug can be taken orally or administered intramuscularly or intravenously. A variety of therapeutic regimens are used; During the selection of the dosage, the doctor must comply with the prescribed treatment regimens for various diseases.

When combined with fluorouracil, the drug is injected at a low speed intravenously (a portion of 0.2 g / m ² ) or through an IV line, followed by a / in the use of fluorouracil in a portion of 0.37 g / m ² ). Medicines 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 the hematological values are stabilized.

[22], [23], [24], [25], [26]

Use Leucovorin during pregnancy

B9-vitamin is contained in the combination of vitamin means prescribed during pregnancy. But special tests to study the effect of Leucovorin on such women were not performed. Therefore, when a need arises to receive a drug, the doctor should decide on his appointment.

[15], [16], [17],

Contraindications

The main contraindications:

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

Caution is necessary in the case of the use of the drug in people with epilepsy, alcoholism or chronic renal failure, and also when prescribing for children.

[18],

Side effects Leucovorin

Administration of the medication can provoke local signs of allergies, sleep disorders, dyspeptic symptoms, a feeling of arousal and depression.

[19], [20], [21]

Interactions with other drugs

The drug weakens the activity of B9-vitamin antagonists and also reduces the anticonvulsant effects of phenobarbital and phenytoin with primidone.

The drug is able to potentiate the toxic and drug properties of fluorouracil, to which it is necessary to pay attention, selecting the dosage of the latter.

It is forbidden to combine leucovorin with infusion liquids containing bicarbonate.

Mixing the drug and droperidol inside a single syringe leads to a precipitate.

[27], [28]

Storage conditions

Leucovorin is required to be kept in a place protected from the ingress of moisture, with a temperature reading of at most 25 ° C.

[29], [30], [31], [32], [33]

Shelf life

Leucovorin can be used within a 36-month period from the time a pharmaceutical product is released.

[34]

Analogs

Analogues of the drug are the substances Leucovorin calcium, Calcium folinate, Leucovorin-Teva, and in addition Leucovorin-LENS with Sanitaryatin and Calcium-folinate-Ebevé.