Adverse Drug Reaction Classification System

Pharmaceutical Information
Drug Name Leucovorin
Drug ID BADD_D01258
Description 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.
Indications and Usage 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.
Marketing Status approved
ATC Code V03AF03
DrugBank ID DB00650
KEGG ID D07986; D07987
MeSH ID D002955
PubChem ID 135403648
TTD Drug ID Not Available
NDC Product Code Not Available
UNII Q573I9DVLP
Synonyms Leucovorin | Folinic Acid-SF | Folinic Acid SF | Leukovorin | Leukovorum | Folinic Acid | Acid, Folinic | Leucovorin, (DL)-Isomer | Citrovorum Factor | Factor, Citrovorum | Calcium Leucovorin | Leucovorin, Calcium | Calcium Folinate | Folinate, Calcium | Leucovorin, (R)-Isomer | Leucovorin, Calcium (1:1) Salt | Leucovorin, Calcium (1:1) Salt, Pentahydrate | Leucovorin, Monosodium Salt | Monosodium Salt Leucovorin | N(5)-Formyltetrahydrofolate | 5-Formyltetrahydropteroylglutamate | 5 Formyltetrahydropteroylglutamate | 5-Formyltetrahydrofolate | 5 Formyltetrahydrofolate | Wellcovorin | Leucovorin, (D)-Isomer | Leucovorin, Calcium (1:1) Salt, (DL)-Isomer
Chemical Information
Molecular Formula C20H23N7O7
CAS Registry Number 58-05-9
SMILES C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
Chemical Structure
ADRs Induced by Drug
*The priority for ADR severity classification is based on FAERS assessment, followed by the most severe level in CTCAE rating. If neither is available, it will be displayed as 'Not available'.
**The 'Not Available' level is hidden by default and can be restored by clicking on the legend twice.
ADR Term ADReCS ID ADR Frequency (FAERS) ADR Severity Grade (FAERS) ADR Severity Grade (CTCAE)
Abdominal adhesions07.07.03.001; 12.02.03.0060.001239%-
Abdominal distension07.01.04.0010.007683%
Abdominal pain07.01.05.0020.025402%
Acidosis14.01.03.0020.001239%
Acute hepatic failure09.01.03.0010.001239%-
Acute myocardial infarction02.02.02.001; 24.04.04.0010.001239%-
Acute respiratory failure14.01.04.004; 22.02.06.0010.001239%-
Alopecia23.02.02.001--
Anaemia01.03.02.0010.006196%
Anaphylactic reaction10.01.07.001; 24.06.03.0060.001859%
Anaphylactic shock10.01.07.002; 24.06.02.004---
Anaphylactoid reaction10.01.07.003; 24.06.03.007---
Anorectal disorder07.03.01.0010.001239%-
Apnoea22.02.01.0010.001239%
Ascites02.05.04.002; 07.07.01.001; 09.01.05.0030.004956%
Asthenia08.01.01.0010.015489%-
Atrial fibrillation02.03.03.0020.005576%
Back pain15.03.04.0050.004337%
Bile duct stone09.02.02.0030.001859%-
Blood creatinine increased13.13.01.004--
Blood pressure fluctuation24.06.01.0020.004213%-
Body temperature increased13.15.01.001---
Bradycardia02.03.02.0020.001239%-
Cardiac arrest02.03.04.0010.003098%
Cardio-respiratory arrest02.03.04.002; 22.02.06.0070.001859%-
Cardiomegaly02.04.02.0010.001859%-
Cataract06.06.01.0010.001239%
Cerebral infarction17.08.01.004; 24.04.06.0020.001859%-
Cerebrovascular accident17.08.01.007; 24.03.05.0010.003965%
Chest discomfort02.02.02.009; 08.01.08.019; 22.12.02.0020.001859%-
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ADReCS-Target
Drug Name ADR Term Target
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