Adverse Drug Reaction Classification System

Pharmaceutical Information
Drug Name Folic acid
Drug ID BADD_D00952
Description Folic acid, also known as folate or Vitamin B9, is a member of the B vitamin family and an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. For example, folic acid is present in green vegetables, beans, avocado, and some fruits.[L5744] In order to function within the body, folic acid 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 by anti-metabolite therapies such as [DB00563] as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. When used in high doses such as for cancer therapy, or in low doses such as for Rheumatoid Arthritis or psoriasis, [DB00563] impedes the body's ability to create folic acid. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects. As a result, supplementation with 1-5mg of folic acid is recommended to prevent deficiency and a number of side effects associated with MTX therapy including mouth ulcers and gastrointestinal irritation. [DB00650] (also known as folinic acid) supplementation is typically used for high-dose MTX regimens for the treatment of cancer. Levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF) and are able to bypass DHFR reduction to act as a cellular replacement for the co-factor THF. There are also several antiepileptic drugs (AEDs) that are associated with reduced serum and red blood cell folate, including [DB00564] (CBZ), [DB00252] (PHT), or barbiturates.[A37004] Folic acid is therefore often provided as supplementation to individuals using these medications, particularly to women of child-bearing age. Inadequate folate levels can result in a number of health concerns including cardiovascular disease, megaloblastic anemias, cognitive deficiencies, and neural tube defects (NTDs). Folic acid is typically supplemented during pregnancy to prevent the development of NTDs and in individuals with alcoholism to prevent the development of neurological disorders, for example.
Indications and Usage For treatment of folic acid deficiency, megaloblastic anemia and in anemias of nutritional supplements, pregnancy, infancy, or childhood.
Marketing Status Prescription; Discontinued
ATC Code B03BB01; V04CX02
DrugBank ID DB00158
KEGG ID D00070
MeSH ID D005492
PubChem ID 135398658
TTD Drug ID D0Z0DW
NDC Product Code 70934-597; 63323-184; 14803-516; 59088-167; 11534-165; 70518-3198; 50268-345; 70518-0866; 68071-2204; 11788-001; 72189-199; 39822-1100; 10135-182; 59088-164; 50090-4953; 68071-4736; 68788-7624; 81919-002; 59088-525; 68071-4175; 55154-2064; 55289-492; 73152-141; 66326-505; 68071-4602; 50090-3581; 43063-791; 59088-176; 50090-4152; 68788-7877; 58657-151; 71335-0766; 63238-3400; 70934-732; 68788-7053; 70518-0609; 53746-361; 62584-897; 62135-210; 59088-193; 50090-3119; 65162-361; 69315-127; 0615-7814; 51552-0418; 71610-235; 50090-2604; 71610-545; 63739-537; 43744-151; 51293-846; 71205-913; 71209-007; 59088-171; 58118-0137; 71335-0613; 59088-186; 70518-3105; 66267-217; 67544-989
Synonyms Folic Acid | Vitamin M | Vitamin B9 | B9, Vitamin | Pteroylglutamic Acid | Folic Acid, Monopotassium Salt | Folic Acid, Monosodium Salt | Folic Acid, Potassium Salt | Folic Acid, (DL)-Isomer | Folvite | Folacin | Folate | Folic Acid, (D)-Isomer | Folic Acid, Calcium Salt (1:1) | Folic Acid, Sodium Salt
Chemical Information
Molecular Formula C19H19N7O6
CAS Registry Number 59-30-3
SMILES C1=CC(=CC=C1C(=O)NC(CCC(=O)O)C(=O)O)NCC2=CN=C3C(=N2)C(=O)NC(=N3)N
Chemical Structure
ADR Related Proteins Induced by Drug
ADR Term Protein Name UniProt AC TTD Target ID PMID
HyperphosphatasaemiaMethylenetetrahydrofolate reductaseQ9WU20Not AvailableNot Available
Liver injuryMethylenetetrahydrofolate reductaseQ9WU20Not AvailableNot Available
ADRs Induced by Drug
ADR Term ADReCS ID ADR Frequency (FAERS) ADR Severity Grade (FAERS) ADR Severity Grade (CTCAE)
Congenital diaphragmatic hernia22.09.02.003; 07.16.01.003; 03.16.03.0010.000153%Not Available
Conjunctivitis11.01.06.012; 06.04.01.0020.000235%
Coordination abnormal17.02.02.0040.000235%Not Available
Cough22.02.03.001--
Crohn's disease10.02.01.005; 07.08.01.0150.000588%Not Available
Cryptorchism21.15.01.001; 05.05.02.002; 03.03.01.0010.000706%Not Available
Deafness04.02.01.0010.000235%Not Available
Death08.04.01.001--
Dehydration14.05.05.0010.000941%
Dementia19.20.02.001; 17.03.01.0010.000353%Not Available
Depressed mood19.15.02.0010.000235%Not Available
Depression19.15.01.001--
Dermatitis23.03.04.002--Not Available
Developmental delay08.01.03.0370.000353%Not Available
Diabetes mellitus14.06.01.001; 05.06.01.0010.000235%Not Available
Diarrhoea07.02.01.001--
Discomfort08.01.08.003--Not Available
Disorientation17.02.05.015; 19.13.01.0020.000235%Not Available
Disturbance in attention17.03.03.001; 19.21.02.0020.000353%
Dizziness24.06.02.007; 17.02.05.003; 02.01.02.004--
Drug hypersensitivity10.01.01.001--Not Available
Drug level decreased13.17.01.007--Not Available
Drug withdrawal syndrome neonatal19.07.02.012; 18.04.13.001; 08.06.02.0080.000353%Not Available
Dry eye06.08.02.0010.000353%
Dry mouth07.06.01.002--
Dysgeusia17.02.07.003; 07.14.03.001--
Dyspepsia07.01.02.0010.000353%
Dysphagia07.01.06.003--
Dyspnoea22.02.01.004; 02.01.03.0020.002470%
Dystonia17.01.03.0010.000353%Not Available
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