leucovorin

Action and Spectrum

Actions and spectrum: 

leucovorin, also known as folinic acid, is a medication used as a rescue therapy after high-dose methotrexate treatment in cancer to decrease the toxicity of the methotrexate and as an adjuvant treatment for colon cancer.

It is also used in combination with 5-fluorouracil for the treatment of colorectal cancer and to enhance the efficacy of chemotherapy regimens in other cancers, such as osteosarcoma and lymphoma.

leucovorin is a derivative of folic acid and works by replenishing depleted levels of folate in the body, which are necessary for DNA synthesis and repair, cell division, and normal hematopoiesis. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Diarrhea 

Vomiting 

Thrombocytosis 

Wheezing 

Anaphylactoid reactions 

Nausea 

Stomatitis 

Anaphylactoid reaction 

Urticaria 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

leucovorin is contraindicated in patients who have shown a previous hypersensitivity to it or to folic acid. It is also contraindicated in the treatment of megaloblastic anemia and pernicious anemias secondary to the lack of vitamin B12.  

Caution: 

• Hypersensitivity: leucovorin should be used with caution in individuals who have a history of hypersensitivity to folic acid or folinic acid. 
• Vitamin B12 deficiency: leucovorin should not be used to treat megaloblastic anemia caused by a deficiency of vitamin B12. 
• Seizure disorders: leucovorin should be used with caution in individuals with a history of seizure disorders, as it may increase the risk of seizures. 
• Renal impairment: leucovorin should be used with caution in individuals with renal impairment, as it may increase the risk of toxicity. 
• Hepatic impairment: leucovorin should be used with caution in individuals with hepatic impairment, as it may increase the risk of toxicity. 
• Gastrointestinal obstruction: leucovorin should be used with caution in individuals with gastrointestinal obstruction, as it may increase the risk of toxicity. 
• Radiation therapy: leucovorin should not be used concomitantly with radiation therapy, as it may decrease the efficacy of the radiation therapy.

Comorbidities: 

leucovorin is often used in combination with chemotherapy drugs to increase its effectiveness in the treatment of various types of cancer. As such, it is important to consider the comorbidities associated with the specific types of cancer being treated. Additionally, since leucovorin is primarily eliminated by the kidneys, caution should be exercised when administering it to patients with impaired renal function.

leucovorin should also be used with caution in patients with folate-dependent tumors, as it may exacerbate the growth of such tumors. Finally, leucovorin may interact with certain medications, such as trimethoprim-sulfamethoxazole, and caution should be exercised when co-administering these drugs. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: C 

Lactation: It is not known whether leucovorin is excreted in human milk  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

leucovorin is a pharmacologically active form of folic acid, a water-soluble B-complex vitamin that is essential for cell growth and development. leucovorin is converted to 5,10-methylene tetrahydrofolate (5,10-MTHF) in the liver and other tissues, which then acts as a co-factor for the enzyme thymidylate synthase. Thymidylate synthase is involved in the synthesis of DNA, and its inhibition by fluoropyrimidines, such as 5-fluorouracil, can be reversed by leucovorin. 

In addition, leucovorin can also rescue normal cells from the toxic effects of high-dose methotrexate therapy by competing with methotrexate for the binding site of dihydrofolate reductase, thereby preventing the depletion of reduced folates necessary for normal cellular functions. leucovorin can also be used as an antidote to folic acid antagonists, such as trimethoprim-sulfamethoxazole and pyrimethamine, by providing a source of reduced folates that are necessary for cell growth and repair.  

Pharmacodynamics: 

leucovorin is a reduced form of folic acid that acts as a coenzyme in the synthesis of nucleotides and thymidylate, which are essential for DNA replication and cell division. leucovorin is rapidly converted to 5,10-methylene tetrahydrofolate, the active form of the drug, in the liver.

The active form of leucovorin enhances the efficacy of fluorouracil, a chemotherapeutic drug, by stabilizing the binding of the drug to thymidylate synthase, which in turn enhances the cytotoxicity of the drug on cancer cells.

leucovorin also enhances the efficacy of other antifolate drugs, such as methotrexate, by increasing the intracellular concentration of reduced folates, which compete with the antifolate drugs for the binding site of dihydrofolate reductase.  

Pharmacokinetics: 

Absorption 

leucovorin is absorbed rapidly and almost completely after oral administration. Following intramuscular injection, it is well absorbed, with peak serum levels usually attained within 1 to 2 hours. When given intravenously, leucovorin is rapidly absorbed into the bloodstream. 

Distribution 

leucovorin is distributed in the extracellular fluid, taken up by the liver, and bound to proteins. It can cross the placenta and is secreted into breast milk. 

Metabolism 

leucovorin is not metabolized. 

Elimination and excretion 

leucovorin is primarily eliminated by the kidneys via glomerular filtration and active tubular secretion. 

Adminstartion

Administration: 

leucovorin can be administered via different routes depending on the indication and the form of the drug. It can be given orally, intravenously, intramuscularly, or as a part of intrathecal chemotherapy. The specific dosing and administration instructions may vary depending on the indication, patient characteristics, and other factors. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: leucovorin 

Pronounced: [ LOO-koe-VOR-in]  

Why do we use leucovorin? 

leucovorin is a medication used to treat or prevent the toxic effects of certain medications or medical conditions. It is commonly used in combination with chemotherapy drugs to enhance the effectiveness of the treatment and reduce its toxic effects on healthy cells.

It is also used to treat folate deficiency and megaloblastic anemia. Additionally, leucovorin is used to treat and prevent toxic effects associated with methotrexate, a medication used in cancer treatment and autoimmune diseases.