folic acid Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	1231	59-30-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: folic acid acifolic aspol cytofol folacid pteroylglutamic acid folate sodium	A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. Molecular weight: 441.40 Formula: C19H19N7O6 CLOGP: -2.04 LIPINSKI: 2 HAC: 13 HDO: 6 TPSA: 207.93 ALOGS: -3.74 ROTB: 9

Molecule

Description

Molfile Inchi Smiles

Synonyms:

folic acid
acifolic
aspol
cytofol
folacid
pteroylglutamic acid
folate sodium

A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.

Molecular weight: 441.40
Formula: C19H19N7O6
CLOGP: -2.04
LIPINSKI: 2
HAC: 13
HDO: 6
TPSA: 207.93
ALOGS: -3.74
ROTB: 9

Drug dosage:

Dose	Unit	Route
0.40	mg	O
10	mg	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.00 mg/mL	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	11.43 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	75 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	9.70 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	52 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.50 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	2.60 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Aug. 13, 1946	FDA	LEDERLE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Pemphigus	2732.82	44.52	358	1437	318	2355972
Systemic lupus erythematosus	2091.23	44.52	360	1435	3861	2352429
Alopecia	1567.18	44.52	373	1422	21628	2334662
Glossodynia	1538.80	44.52	249	1546	1696	2354594
Abdominal discomfort	1433.98	44.52	333	1462	17123	2339167
Rheumatoid arthritis	1387.53	44.52	330	1465	18810	2337480
Pain	1240.85	44.52	386	1409	61471	2294819
Hand deformity	933.91	44.52	150	1645	936	2355354
Maternal exposure during pregnancy	930.13	44.52	229	1566	14634	2341656
Drug ineffective	872.84	44.52	338	1457	101286	2255004
Contraindicated product administered	700.06	44.52	137	1658	2884	2353406
Fatigue	687.24	44.52	272	1523	84601	2271689
Hip arthroplasty	626.83	44.52	116	1679	1778	2354512
Swelling	625.85	44.52	171	1624	16179	2340111
Knee arthroplasty	582.13	44.52	117	1678	2818	2353472
Exposure during pregnancy	497.68	44.52	158	1637	25061	2331229
Wound	407.00	44.52	86	1709	2642	2353648
Condition aggravated	406.31	44.52	144	1651	31835	2324455
Drug intolerance	385.00	44.52	113	1682	13604	2342686
Loss of personal independence in daily activities	294.77	44.52	75	1720	5236	2351054
Joint swelling	236.34	44.52	82	1713	16737	2339553
Anti-cyclic citrullinated peptide antibody positive	231.95	44.52	36	1759	167	2356123
Foetal exposure during pregnancy	227.68	44.52	61	1734	5191	2351099
Premature delivery	221.47	44.52	54	1741	3146	2353144
Treatment failure	203.89	44.52	60	1735	7179	2349111
Product use issue	177.12	44.52	61	1734	12108	2344182
Rash	172.00	44.52	95	1700	59463	2296827
Arthropathy	168.71	44.52	52	1743	7264	2349026
Live birth	148.78	44.52	33	1762	1258	2355032
Synovitis	148.47	44.52	38	1757	2688	2353602
Rheumatoid factor positive	141.18	44.52	27	1768	485	2355805
Discomfort	137.41	44.52	41	1754	5118	2351172
Haematocrit decreased	135.61	44.52	39	1756	4279	2352011
Infusion related reaction	134.27	44.52	47	1748	9749	2346541
Pneumonia aspiration	122.88	44.52	35	1760	3707	2352583
Coma	122.36	44.52	43	1752	9013	2347277
Gastrooesophageal reflux disease	122.18	44.52	43	1752	9052	2347238
Haemoglobin decreased	119.24	44.52	51	1744	18100	2338190
Somnolence	119.03	44.52	55	1740	23430	2332860
Arthralgia	112.46	44.52	70	1725	54215	2302075
Pericarditis	106.44	44.52	26	1769	1514	2354776
Hepatic enzyme increased	100.56	44.52	38	1757	9764	2346526
Completed suicide	99.51	44.52	47	1748	20987	2335303
Red blood cell count decreased	88.46	44.52	28	1767	4238	2352052
Tenderness	86.33	44.52	23	1772	1895	2354395
Abortion spontaneous	85.63	44.52	37	1758	13408	2342882
Developmental hip dysplasia	84.51	44.52	15	1780	174	2356116
Hypersensitivity	82.68	44.52	43	1752	23550	2332740
Pregnancy	82.16	44.52	31	1764	7918	2348372
Grip strength decreased	78.93	44.52	19	1776	1038	2355252
Spinal stenosis	78.27	44.52	20	1775	1398	2354892
Vomiting	75.05	44.52	61	1734	71541	2284749
Premature baby	74.66	44.52	23	1772	3181	2353109
Disability	72.78	44.52	17	1778	815	2355475
Foetal death	72.35	44.52	20	1775	1892	2354398
Body mass index decreased	64.79	44.52	10	1785	44	2356246
Duodenal ulcer perforation	63.95	44.52	13	1782	322	2355968
Therapeutic product effect decreased	63.16	44.52	28	1767	10761	2345529
Pre-eclampsia	62.79	44.52	17	1778	1487	2354803
Fall	62.03	44.52	46	1749	47053	2309237
Hyperkalaemia	60.93	44.52	23	1772	5870	2350420
Adverse event	58.47	44.52	24	1771	7635	2348655
Red blood cell sedimentation rate abnormal	58.18	44.52	13	1782	510	2355780
Drug hypersensitivity	57.94	44.52	44	1751	46599	2309691
Forceps delivery	57.70	44.52	9	1786	43	2356247
Caesarean section	57.41	44.52	20	1775	4061	2352229
Haemorrhage in pregnancy	57.37	44.52	12	1783	343	2355947
Osteoarthritis	57.25	44.52	23	1772	6923	2349367
Gait disturbance	56.59	44.52	33	1762	22512	2333778
Therapeutic response decreased	56.47	44.52	23	1772	7172	2349118
Helicobacter infection	56.23	44.52	13	1782	595	2355695
Arthritis	55.55	44.52	25	1770	9943	2346347
Off label use	53.51	44.52	51	1744	73547	2282743
Hypertension	53.17	44.52	34	1761	27327	2328963
Monocyte count increased	52.32	44.52	12	1783	530	2355760
Diarrhoea	51.66	44.52	53	1742	83511	2272779
Nasopharyngitis	49.38	44.52	30	1765	22026	2334264
C-reactive protein increased	49.09	44.52	20	1775	6235	2350055
Sciatica	48.41	44.52	15	1780	2110	2354180
Haemodynamic instability	47.68	44.52	13	1782	1166	2355124
Toxicity to various agents	47.61	44.52	34	1761	32720	2323570
Viral infection	47.41	44.52	18	1777	4658	2351632
Contusion	46.66	44.52	24	1771	12786	2343504
Metabolic acidosis	46.46	44.52	19	1776	5979	2350311
Premature rupture of membranes	46.19	44.52	12	1783	894	2355396
Abdominal pain	46.14	44.52	34	1761	34340	2321950
Pain in extremity	46.01	44.52	37	1758	42503	2313787

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Foetal exposure during pregnancy	562.13	44.66	124	739	6235	1739683
Premature baby	375.24	44.66	78	785	2864	1743054
Low birth weight baby	219.06	44.66	41	822	846	1745072
Arthralgia	188.82	44.66	71	792	23373	1722545
Pain	115.59	44.66	52	811	26605	1719313
Foetal disorder	108.87	44.66	16	847	63	1745855
Completed suicide	90.67	44.66	38	825	16274	1729644
Hypotension	89.08	44.66	45	818	29609	1716309
Neutropenia neonatal	84.40	44.66	12	851	35	1745883
Drug ineffective	82.63	44.66	56	807	63745	1682173
Rheumatoid arthritis	76.04	44.66	24	839	4561	1741357
Steatorrhoea	73.57	44.66	12	851	104	1745814
Drug intolerance	73.37	44.66	25	838	6037	1739881
Weight decrease neonatal	72.04	44.66	10	853	23	1745895
Liver function test abnormal	70.80	44.66	24	839	5702	1740216
Nasopharyngitis	68.09	44.66	27	836	9983	1735935
Therapeutic product effect decreased	64.74	44.66	23	840	6274	1739644
Joint swelling	60.77	44.66	22	841	6331	1739587
Seizure	58.20	44.66	30	833	20411	1725507
Gangrene neonatal	57.83	44.66	7	856	1	1745917
Medical device implantation	57.64	44.66	9	854	57	1745861
Loss of personal independence in daily activities	54.45	44.66	16	847	2383	1743535
Exposure via breast milk	51.19	44.66	10	853	256	1745662
Infusion related reaction	49.05	44.66	19	844	6574	1739344
Condition aggravated	48.79	44.66	27	836	21123	1724795
Genitalia external ambiguous	48.35	44.66	7	856	24	1745894
Leukopenia	47.76	44.66	20	843	8460	1737458
Congenital bladder anomaly	47.31	44.66	7	856	29	1745889
Maternal exposure during breast feeding	47.17	44.66	10	853	388	1745530
Insomnia	46.59	44.66	24	839	16252	1729666
Overdose	46.00	44.66	24	839	16677	1729241
Peripheral swelling	45.56	44.66	19	844	7952	1737966
Hepatic enzyme increased	45.44	44.66	18	845	6603	1739315

Pharmacologic Action:

Source	Code	Description
ATC	B03BB01	BLOOD AND BLOOD FORMING ORGANS ANTIANEMIC PREPARATIONS VITAMIN B12 AND FOLIC ACID Folic acid and derivatives
ATC	V04CX02	VARIOUS DIAGNOSTIC AGENTS OTHER DIAGNOSTIC AGENTS Other diagnostic agents
ATC	B03AE01	BLOOD AND BLOOD FORMING ORGANS ANTIANEMIC PREPARATIONS IRON PREPARATIONS Iron in other combinations
ATC	B03AE02	BLOOD AND BLOOD FORMING ORGANS ANTIANEMIC PREPARATIONS IRON PREPARATIONS Iron in other combinations
ATC	B03BB51	BLOOD AND BLOOD FORMING ORGANS ANTIANEMIC PREPARATIONS VITAMIN B12 AND FOLIC ACID Folic acid and derivatives
MeSH PA	D006397	Hematinics
MeSH PA	D006401	Hematologic Agents
MeSH PA	D018977	Micronutrients
CHEBI has role	CHEBI:75769	B vitamin
MeSH PA	D014803	Vitamin B Complex
MeSH PA	D014815	Vitamins

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Megaloblastic anemia due to folate deficiency	indication	85649008	DOID:14026
Vitamin deficiency	indication	85670002
Iron deficiency anemia	indication	87522002
Mineral deficiency	indication	111379007
Folic acid deficiency	indication	190633005
Pregnancy, function	indication	289908002
Breastfeeding (mother)	indication	413712001
Vitamin Deficiency Prevention	indication
Mineral Deficiency Prevention	indication
Prevention of Vitamin B12 Deficiency	indication
Homocystinuria	off-label use	11282001	DOID:9263
Homocystinemia	off-label use	52311001
Prevention of Fetal Neural Tube Defects during Pregnancy	off-label use
Peptic ulcer	contraindication	13200003	DOID:750
Bipolar disorder	contraindication	13746004	DOID:3312
Constipation	contraindication	14760008	DOID:2089
Operation on stomach	contraindication	16453004
Primary hyperoxaluria	contraindication	17901006	DOID:2977
Gastroenteritis	contraindication	25374005	DOID:2326
Sarcoidosis	contraindication	31541009	DOID:11335
Dehydration	contraindication	34095006
Hemosiderosis	contraindication	39011001	DOID:12119
Hypokalemia	contraindication	43339004
Gastrectomy	contraindication	53442002
Leber's optic atrophy	contraindication	58610003	DOID:705
Hemolytic anemia	contraindication	61261009	DOID:583
Diarrhea	contraindication	62315008
Ulcerative colitis	contraindication	64766004	DOID:8577
Hypercalcemia	contraindication	66931009	DOID:12678
Hyperparathyroidism	contraindication	66999008	DOID:13543
Diabetes mellitus	contraindication	73211009	DOID:9351
Phototoxicity	contraindication	84326006
Atrophic gastritis	contraindication	84568007	DOID:8929
Kidney disease	contraindication	90708001	DOID:557
Kidney stone	contraindication	95570007
Anemia due to enzyme deficiency	contraindication	111577008
Hb SS disease	contraindication	127040003	DOID:10923
Osteolysis	contraindication	203522001
Hypomania	contraindication	231496004
Esophageal dysmotility	contraindication	266434009	DOID:9192
Diverticular disease	contraindication	397881000
Hemochromatosis	contraindication	399187006	DOID:2352
Repeated Blood Transfusions	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.46	acidic
pKa2	5.15	acidic
pKa3	12.96	acidic
pKa4	4.55	Basic
pKa5	4.15	Basic
pKa6	2.28	Basic
pKa7	1.73	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Thymidylate synthase	Enzyme	P04818	TYSY_HUMAN		Ki	4.40		CHEMBL
Dihydrofolate reductase	Unclassified		B0BL08_ECOLX		Kd	6.09		CHEMBL

External reference:

ID	Source
D005492	MESH_DESCRIPTOR_UI
4017507	VUID
N0000145892	NUI
C0016410	UMLSCUI
D00070	KEGG_DRUG
6247001	SNOMEDCT_US
264	MMSL
4511	RXNORM
63718003	SNOMEDCT_US
4759	MMSL
d00241	MMSL
4017507	VANDF
001049	NDDF
935E97BOY8	UNII
68	INN_ID
6484-89-5	SECONDARY_CAS_RN
DB00158	DRUGBANK_ID
CHEMBL1622	ChEMBL_ID
FOL	PDB_CHEM_ID
CHEBI:27470	CHEBI
CHEMBL2107429	ChEMBL_ID
135398658	PUBCHEM_CID
4563	IUPHAR_LIGAND_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Ferralet 90	HUMAN PRESCRIPTION DRUG LABEL	5	0178-0089	TABLET, FILM COATED	1 mg	ORAL	unapproved drug other	14 sections
NataFort	HUMAN PRESCRIPTION DRUG LABEL	10	0178-0716	TABLET	1 mg	ORAL	Unapproved drug other	12 sections
CitraNatal Harmony 3.0	HUMAN PRESCRIPTION DRUG LABEL	7	0178-0796	CAPSULE, GELATIN COATED	1 mg	ORAL	unapproved drug other	10 sections
CitraNatal Harmony	HUMAN PRESCRIPTION DRUG LABEL	8	0178-0798	CAPSULE, GELATIN COATED	1 mg	ORAL	UNAPPROVED DRUG OTHER	12 sections
CitraNatal Harmony	HUMAN PRESCRIPTION DRUG LABEL	8	0178-0799	CAPSULE, GELATIN COATED	1 mg	ORAL	Unapproved drug other	11 sections
CitraNatal Harmony	HUMAN PRESCRIPTION DRUG LABEL	8	0178-0812	CAPSULE, GELATIN COATED	1 mg	ORAL	Unapproved drug other	11 sections
CitraNatal Bloom	HUMAN PRESCRIPTION DRUG LABEL	6	0178-0813	TABLET, FILM COATED	1.40 mg	ORAL	unapproved drug other	13 sections
CitraNatal Bloom DHA	HUMAN PRESCRIPTION DRUG LABEL	6	0178-0816	KIT	1 mg	ORAL	unapproved drug other	10 sections
CitraNatal 90 DHA	HUMAN PRESCRIPTION DRUG LABEL	13	0178-0821	TABLET	1 mg	ORAL	unapproved drug other	10 sections
CitraNatal 90 DHA	HUMAN OTC DRUG LABEL	10	0178-0829	TABLET	1 mg	ORAL	Unapproved drug other	10 sections
CITRANATAL B-CALM	HUMAN PRESCRIPTION DRUG LABEL	6	0178-0832	KIT	1 mg	None	unapproved drug other	11 sections
CitraNatal Rx	HUMAN PRESCRIPTION DRUG LABEL	11	0178-0858	TABLET	1 mg	ORAL	Unapproved drug other	11 sections
CitraNatal Rx	HUMAN PRESCRIPTION DRUG LABEL	12	0178-0859	TABLET	1 mg	ORAL	Unapproved drug other	8 sections
CitraNatal	HUMAN PRESCRIPTION DRUG LABEL	7	0178-0866	KIT	1 mg	None	Unapproved drug other	11 sections
CitraNatal Assure	HUMAN PRESCRIPTION DRUG LABEL	13	0178-0891	KIT	1 mg	None	unapproved drug other	12 sections
CitraNatal Assure	HUMAN PRESCRIPTION DRUG LABEL	14	0178-0893	KIT	1 mg	None	Unapproved drug other	12 sections
CitraNatal DHA	HUMAN PRESCRIPTION DRUG LABEL	14	0178-0894	KIT	1 mg	None	unapproved drug other	11 sections
CitraNatal Medley	HUMAN PRESCRIPTION DRUG LABEL	7	0178-0896	CAPSULE, GELATIN COATED	1 mg	ORAL	unapproved drug other	9 sections
CitraNatal DHA	HUMAN OTC DRUG LABEL	12	0178-0898	TABLET	1 mg	ORAL	Unapproved drug other	10 sections
Folic Acid	HUMAN PRESCRIPTION DRUG LABEL	1	0603-3162	TABLET	1 mg	ORAL	ANDA	12 sections
Folbic	HUMAN PRESCRIPTION DRUG LABEL	3	0615-7575	TABLET	2.50 mg	ORAL	UNAPPROVED DRUG OTHER	10 sections
Folic Acid	HUMAN PRESCRIPTION DRUG LABEL	1	0615-7814	TABLET	1 mg	ORAL	ANDA	12 sections
Vitafol	HUMAN PRESCRIPTION DRUG LABEL	11	0642-0070	CAPSULE, GELATIN COATED	1 mg	ORAL	unapproved drug other	6 sections
Vitafol	HUMAN PRESCRIPTION DRUG LABEL	9	0642-0072	CAPSULE	1 mg	ORAL	UNAPPROVED DRUG OTHER	9 sections
Select-OB Plus DHA	HUMAN PRESCRIPTION DRUG LABEL	15	0642-0075	KIT	0.40 mg	None	Unapproved drug other	10 sections
Vitafol-OB Plus DHA	HUMAN PRESCRIPTION DRUG LABEL	10	0642-0076	KIT	1 mg	None	Unapproved drug other	13 sections
Select OB	HUMAN PRESCRIPTION DRUG LABEL	11	0642-0077	TABLET, CHEWABLE	0.40 mg	ORAL	UNAPPROVED DRUG OTHER	11 sections
Vitafol OB	HUMAN PRESCRIPTION DRUG LABEL	9	0642-0079	TABLET	1 mg	ORAL	Unapproved drug other	11 sections
Vitafol	HUMAN PRESCRIPTION DRUG LABEL	12	0642-0092	CAPSULE, LIQUID FILLED	1 mg	ORAL	UNAPPROVED DRUG OTHER	10 sections
Vitafol	HUMAN PRESCRIPTION DRUG LABEL	16	0642-0093	CAPSULE, LIQUID FILLED	0.40 mg	ORAL	UNAPPROVED DRUG OTHER	10 sections