Leucovorin calcium USP

Leucovorin calcium USP Uses, Dosage, Side Effects, Food Interaction and all others data.

Folinic Acid (also known as 5-formyl tetrahydrofolic acid or leucovorin) is the 5-formyl derivative of tetrahydrofolic acid, a necessary co-factor in the body. Commercially available leucovorin is composed of a 1:1 racemic mixture of the dextrorotary and levorotary isomers, while levoleucovorin contains only the pharmacologically active levo-isomer. In vitro, the levo-isomer has been shown to be rapidly converted to the biologically available methyl-tetrahydrofolate form while the dextro form is slowly excreted by the kidneys. Despite this difference in activity, the two commercially available forms have been shown to be pharmacokinetically identical and may be used interchangeably with limited differences in efficacy or side effects (Kovoor et al, 2009).

As folate analogs, leucovorin and levoleucovorin are both used to counteract the toxic effects of folic acid antagonists, such as methotrexate, which act by inhibiting the enzyme dihydrofolate reductase (DHFR). They are indicated for use as rescue therapy following use of high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Injectable forms are also indicated for use in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible and for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

Folic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects associated with methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.

Leucovorin calcium USP
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Leucovorin calcium USP
Availability	Prescription only
Generic	Leucovorin
Leucovorin Other Names	5-Formyltetrahydrofolate, Acide folinique, Acido folinico, Folinate, Folinic acid, Leucovorinum
Related Drugs	azithromycin, clindamycin, sulfamethoxazole / trimethoprim, Bactrim, folic acid, Zithromax, clarithromycin, Bactrim DS, Keytruda, capecitabine
Type
Formula	C₂₀H₂₃N₇O₇
Weight	Average: 473.446 Monoisotopic: 473.165896109
Protein binding	~15%
Groups	Approved
Therapeutic Class
Manufacturer
Available Country	Canada
Last Updated:	September 19, 2023 at 7:00 am

Uses

Leucovorin calcium USP is a folate analog used to treat the toxic effects of methotrexate and other folate antagonists, to treat megaloblastic anemia, and to provide palliative treatment of colorectal cancer.

For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

Leucovorin calcium USP is also used to associated treatment for these conditions: Advanced Colorectal Cancer, Advanced Esophageal Cancers, Advanced Gastric Cancer, Anemia of Pregnancy, Cancer, Bladder, Folate and iron deficiency, Folate deficiency, Folic acid antagonist overdose, Iron Deficiency (ID), Macrocytic anemia, Megaloblastic anemia, Pancreatic Cancer Metastatic, Postpartum Anemia, Hypochromic anemia, Methotrexate toxicity, Normochromic anemia, Pyrimethamine hematologic toxicity

How Leucovorin calcium USP works

As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin calcium USP enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.

Toxicity

LD₅₀>8000 mg/kg (orally in rats). Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.

Food Interaction

No interactions found.

Leucovorin calcium USP Disease Interaction

Major: anemia, GI toxicityModerate: renal impairment, seizures

Elimination Route

Following oral administration, leucovorin is rapidly absorbed. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg.