leucovorin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	1232	58-05-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: sodium folinate folinic acid leucovorin calcium folinate leucovorin calcium folinic acid calcium salt folinic acid calcium wellcovorin folinic acid calcium salt pentahydrate	The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS. Molecular weight: 473.45 Formula: C20H23N7O7 CLOGP: -3.49 LIPINSKI: 2 HAC: 14 HDO: 7 TPSA: 215.55 ALOGS: -3.20 ROTB: 9 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

sodium folinate
folinic acid
leucovorin
calcium folinate
leucovorin calcium
folinic acid calcium salt
folinic acid calcium
wellcovorin
folinic acid calcium salt pentahydrate

The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS.

Molecular weight: 473.45
Formula: C20H23N7O7
CLOGP: -3.49
LIPINSKI: 2
HAC: 14
HDO: 7
TPSA: 215.55
ALOGS: -3.20
ROTB: 9

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
60	mg	O
60	mg	P
60	mg	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	500 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	10 %	Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability)	4 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.25 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	5.80 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.09 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1.30 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
June 20, 1952	FDA

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
Neutropenia	1560.82	50.55	457	4210	21091	2332327
Diarrhoea	1371.44	50.55	585	4082	82979	2270439
Vomiting	883.76	50.55	413	4254	71189	2282229
Nausea	781.97	50.55	440	4227	111749	2241669
Febrile neutropenia	770.22	50.55	228	4439	10654	2342764
Thrombocytopenia	594.39	50.55	215	4452	18916	2334502
Mucosal inflammation	589.95	50.55	158	4509	5066	2348352
Abdominal pain	586.42	50.55	250	4417	34124	2319294
Stomatitis	534.73	50.55	168	4499	9542	2343876
Neuropathy peripheral	532.00	50.55	174	4493	11258	2342160
Dehydration	491.10	50.55	195	4472	22100	2331318
Pulmonary embolism	439.61	50.55	170	4497	17913	2335505
Pyrexia	425.76	50.55	231	4436	53477	2299941
Leukopenia	425.27	50.55	143	4524	10053	2343365
Anaemia	410.65	50.55	196	4471	34596	2318822
Neurotoxicity	406.10	50.55	98	4569	2032	2351386
Hypertension	387.53	50.55	175	4492	27186	2326232
Disease progression	384.55	50.55	152	4515	16943	2336475
General physical health deterioration	361.43	50.55	138	4529	14001	2339417
Asthenia	357.97	50.55	197	4470	46729	2306689
Malignant neoplasm progression	294.12	50.55	114	4553	12014	2341404
Fatigue	279.95	50.55	210	4457	84663	2268755
Posterior reversible encephalopathy syndrome	255.92	50.55	70	4597	2410	2351008
Hypokalaemia	254.16	50.55	99	4568	10555	2342863
Sepsis	229.07	50.55	108	4559	18380	2335038
Off label use	226.55	50.55	175	4492	73423	2279995
Polyneuropathy	192.28	50.55	52	4615	1711	2351707
Palmar-plantar erythrodysaesthesia syndrome	186.96	50.55	62	4605	4139	2349279
Decreased appetite	186.28	50.55	109	4558	28782	2324636
Bone marrow failure	172.30	50.55	63	4604	5623	2347795
Haemoglobin decreased	165.13	50.55	86	4581	18065	2335353
Hypomagnesaemia	155.90	50.55	48	4619	2516	2350902
Ileus	154.99	50.55	46	4621	2126	2351292
Dyspnoea	153.07	50.55	144	4523	78589	2274829
Device related infection	152.61	50.55	50	4617	3209	2350209
Urinary tract infection	147.05	50.55	95	4572	29847	2323571
Haematotoxicity	139.40	50.55	37	4630	1130	2352288
Colorectal cancer metastatic	135.64	50.55	26	4641	165	2353253
Peripheral sensory neuropathy	134.27	50.55	35	4632	995	2352423
White blood cell count decreased	134.07	50.55	75	4592	18133	2335285
Metastases to liver	133.19	50.55	44	4623	2897	2350521
Respiratory failure	131.33	50.55	67	4600	13461	2339957
Deep vein thrombosis	131.24	50.55	66	4601	12866	2340552
Pancytopenia	126.73	50.55	62	4605	11390	2342028
Septic shock	124.92	50.55	53	4614	7001	2346417
Neoplasm progression	124.08	50.55	47	4620	4621	2348797
Interstitial lung disease	122.95	50.55	54	4613	7758	2345660
Enteritis	122.93	50.55	33	4634	1053	2352365
Acute kidney injury	122.91	50.55	83	4584	28039	2325379
Chills	122.53	50.55	67	4600	15485	2337933
Hypotension	119.04	50.55	86	4581	32350	2321068
Pneumonia	118.93	50.55	102	4565	49194	2304224
Gastrointestinal toxicity	116.87	50.55	28	4639	558	2352860
Intestinal obstruction	108.74	50.55	42	4625	4351	2349067
Proteinuria	106.82	50.55	37	4630	2813	2350605
Multiple organ dysfunction syndrome	104.86	50.55	48	4619	7593	2345825
Infection	102.92	50.55	63	4604	17966	2335452
Platelet count decreased	102.58	50.55	60	4607	15753	2337665
Renal failure	102.57	50.55	62	4605	17287	2336131
Alopecia	101.03	50.55	67	4600	21934	2331484
Neutrophil count decreased	98.82	50.55	44	4623	6523	2346895
Intestinal perforation	98.24	50.55	31	4636	1760	2351658
Constipation	97.22	50.55	65	4602	21564	2331854
Toxicity to various agents	96.09	50.55	76	4591	32678	2320740
Small intestinal obstruction	95.65	50.55	32	4635	2188	2351230
Skin toxicity	94.11	50.55	25	4642	765	2352653
Atrial fibrillation	93.96	50.55	54	4613	13714	2339704
Maternal exposure during pregnancy	92.73	50.55	55	4612	14808	2338610
Ascites	92.14	50.55	40	4627	5580	2347838
Chest pain	90.59	50.55	69	4598	28068	2325350
Dermatitis acneiform	88.81	50.55	24	4643	785	2352633
Metastases to lung	86.86	50.55	28	4639	1703	2351715
Epistaxis	84.99	50.55	45	4622	9734	2343684
Paraesthesia	84.22	50.55	60	4607	22028	2331390
Hypersensitivity	82.92	50.55	61	4606	23532	2329886
Seizure	78.73	50.55	60	4607	24406	2329012
Arteriospasm coronary	78.39	50.55	21	4646	664	2352754
Rash	77.45	50.55	88	4579	59470	2293948
Death	74.78	50.55	101	4566	81367	2272051
Metastases to meninges	74.31	50.55	18	4649	376	2353042
Clostridium difficile colitis	74.08	50.55	26	4641	2053	2351365
Syncope	74.07	50.55	50	4617	16825	2336593
Pain	73.07	50.55	87	4580	61770	2291648
Pleural effusion	72.29	50.55	43	4624	11625	2341793
Abdominal pain upper	70.65	50.55	54	4613	22046	2331372
Paronychia	70.08	50.55	20	4647	802	2352616
Embolism	68.99	50.55	22	4645	1291	2352127
Neoplasm recurrence	67.94	50.55	17	4650	408	2353010
Hypophagia	67.29	50.55	29	4638	3971	2349447
Nasal septum perforation	66.59	50.55	14	4653	149	2353269
Cardiomyopathy	66.48	50.55	26	4641	2781	2350637
Hydronephrosis	65.63	50.55	21	4646	1246	2352172
Splenomegaly	65.39	50.55	22	4645	1529	2351889
Cholangitis	64.41	50.55	19	4648	857	2352561
Encephalopathy	63.63	50.55	29	4638	4532	2348886
Blood creatinine increased	63.11	50.55	38	4629	10495	2342923
Aortic thrombosis	62.79	50.55	14	4653	200	2353218
Hyperammonaemic encephalopathy	61.89	50.55	15	4652	314	2353104
Large intestine perforation	61.62	50.55	20	4647	1242	2352176
Pulmonary oedema	61.47	50.55	33	4634	7330	2346088
Multiple-drug resistance	61.14	50.55	14	4653	227	2353191
Tumour lysis syndrome	60.58	50.55	19	4648	1056	2352362
Cholestasis	59.40	50.55	26	4641	3695	2349723
Neutropenic sepsis	59.00	50.55	20	4647	1422	2351996
Dysphagia	58.71	50.55	39	4628	12766	2340652
Product use in unapproved indication	58.45	50.55	37	4630	11163	2342255
Cystitis radiation	58.15	50.55	9	4658	10	2353408
Human bocavirus infection	57.69	50.55	9	4658	11	2353407
Venoocclusive liver disease	57.29	50.55	16	4651	592	2352826
Acute lymphocytic leukaemia recurrent	56.58	50.55	13	4654	214	2353204
Premature delivery	56.46	50.55	24	4643	3176	2350242
Gastrointestinal disorder	55.57	50.55	33	4634	8884	2344534
Alanine aminotransferase increased	55.48	50.55	39	4628	13993	2339425
Hypocalcaemia	55.15	50.55	25	4642	3858	2349560
Hyponatraemia	54.94	50.55	38	4629	13287	2340131
Dysphonia	54.46	50.55	29	4638	6335	2347083
Colorectal cancer	54.39	50.55	13	4654	256	2353162
Enterobacter infection	54.15	50.55	13	4654	261	2353157
Colitis	53.90	50.55	27	4640	5199	2348219
Pneumothorax	53.28	50.55	21	4646	2291	2351127
Superior vena cava syndrome	53.03	50.55	11	4656	109	2353309
Bladder tamponade	52.65	50.55	9	4658	26	2353392
Venous thrombosis	52.55	50.55	16	4651	805	2352613
Herpes simplex	52.46	50.55	17	4650	1050	2352368
Dysarthria	51.91	50.55	28	4639	6274	2347144
Hemiparesis	51.50	50.55	23	4644	3427	2349991
Stress cardiomyopathy	51.01	50.55	18	4649	1443	2351975
Blood alkaline phosphatase increased	50.92	50.55	28	4639	6517	2346901

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
Diarrhoea	1934.68	48.45	843	5805	53009	1687124
Neutropenia	1537.52	48.45	534	6114	17726	1722407
Neuropathy peripheral	908.69	48.45	305	6343	8948	1731185
Nausea	863.11	48.45	483	6165	50713	1689420
Pyrexia	798.12	48.45	444	6204	45956	1694177
Vomiting	764.80	48.45	405	6243	37910	1702223
Febrile neutropenia	690.55	48.45	261	6387	10839	1729294
Abdominal pain	662.35	48.45	306	6342	21184	1718949
Thrombocytopenia	618.72	48.45	291	6357	20958	1719175
Dehydration	608.59	48.45	272	6376	17386	1722747
Decreased appetite	592.46	48.45	293	6355	23578	1716555
Mucosal inflammation	569.71	48.45	177	6471	3992	1736141
Fatigue	511.07	48.45	346	6302	50435	1689698
General physical health deterioration	473.46	48.45	209	6439	12909	1727224
Disease progression	472.83	48.45	227	6421	17036	1723097
Stomatitis	454.29	48.45	159	6489	5245	1734888
Asthenia	430.51	48.45	270	6378	34400	1705733
Metastases to liver	398.60	48.45	117	6531	2150	1737983
Off label use	387.25	48.45	263	6385	38308	1701825
Pulmonary embolism	385.52	48.45	181	6467	12878	1727255
Palmar-plantar erythrodysaesthesia syndrome	344.38	48.45	116	6532	3391	1736742
Leukopenia	331.09	48.45	143	6505	8337	1731796
Anaemia	326.80	48.45	214	6434	29243	1710890
Hypertension	322.84	48.45	183	6465	19265	1720868
Chills	314.23	48.45	152	6496	11535	1728598
Malignant neoplasm progression	312.43	48.45	161	6487	13997	1726136
Interstitial lung disease	309.54	48.45	142	6506	9554	1730579
Acute kidney injury	298.25	48.45	216	6432	34728	1705405
Sepsis	267.30	48.45	162	6486	19276	1720857
Dermatitis acneiform	265.16	48.45	72	6576	980	1739153
Neurotoxicity	255.43	48.45	81	6567	1943	1738190
Skin toxicity	253.74	48.45	62	6586	537	1739596
Constipation	245.52	48.45	140	6508	14860	1725273
Peripheral sensory neuropathy	221.98	48.45	60	6588	801	1739332
Colorectal cancer metastatic	220.97	48.45	47	6601	199	1739934
Ascites	220.41	48.45	95	6553	5491	1734642
Intestinal obstruction	219.06	48.45	83	6565	3424	1736709
Dyspnoea	200.47	48.45	204	6444	51855	1688278
Small intestinal obstruction	197.38	48.45	65	6583	1762	1738371
Deep vein thrombosis	193.45	48.45	104	6544	9816	1730317
Proteinuria	191.01	48.45	71	6577	2773	1737360
Neoplasm progression	188.53	48.45	73	6575	3194	1736939
Epistaxis	184.45	48.45	95	6553	8211	1731922
Skin reaction	182.15	48.45	55	6593	1113	1739020
Alopecia	182.14	48.45	74	6574	3679	1736454
Weight decreased	180.78	48.45	135	6513	22618	1717515
Urinary tract infection	177.39	48.45	99	6549	10054	1730079
Pneumonia	172.20	48.45	178	6470	46004	1694129
Metastases to lung	171.39	48.45	56	6592	1479	1738654
Hypokalaemia	165.27	48.45	81	6567	6293	1733840
Polyneuropathy	164.03	48.45	56	6592	1699	1738434
Hypotension	159.34	48.45	140	6508	29514	1710619
Paraesthesia	158.68	48.45	93	6555	10358	1729775
Respiratory failure	156.84	48.45	104	6544	14401	1725732
Ileus	149.47	48.45	57	6591	2389	1737744
Gastrointestinal toxicity	147.68	48.45	37	6611	358	1739775
Bone marrow failure	140.53	48.45	68	6580	5132	1735001
Haemoglobin decreased	139.04	48.45	103	6545	17011	1723122
Tachycardia	137.58	48.45	91	6557	12537	1727596
Neutrophil count decreased	136.21	48.45	70	6578	6011	1734122
Oesophagitis	134.80	48.45	48	6600	1653	1738480
Paronychia	133.59	48.45	37	6611	543	1739590
Renal failure	128.95	48.45	105	6543	19912	1720221
Infection	127.25	48.45	86	6562	12274	1727859
Cholangitis	127.17	48.45	42	6606	1147	1738986
Abdominal pain lower	126.55	48.45	42	6606	1165	1738968
Rash	126.06	48.45	139	6509	38554	1701579
Device related infection	124.49	48.45	49	6599	2237	1737896
Septic shock	122.60	48.45	72	6576	8037	1732096
Chest pain	118.95	48.45	100	6548	19814	1720319
Hiccups	118.24	48.45	42	6606	1435	1738698
Blood creatinine increased	115.61	48.45	85	6563	13861	1726272
C-reactive protein increased	115.44	48.45	62	6586	5823	1734310
Circulatory collapse	114.22	48.45	52	6596	3415	1736718
Pleural effusion	113.62	48.45	77	6571	11033	1729100
Colitis	110.92	48.45	54	6594	4126	1736007
Hypoalbuminaemia	103.69	48.45	38	6610	1422	1738711
Enteritis	102.39	48.45	34	6614	944	1739189
Blood bilirubin increased	101.44	48.45	58	6590	6152	1733981
Proteus infection	101.42	48.45	22	6626	104	1740029
Portal hypertension	101.35	48.45	31	6617	655	1739478
Tumour lysis syndrome	100.51	48.45	39	6609	1712	1738421
Intestinal perforation	99.86	48.45	38	6610	1581	1738552
Neutropenic sepsis	99.21	48.45	37	6611	1455	1738678
Colorectal cancer	97.10	48.45	27	6621	402	1739731
Necrotising fasciitis	94.49	48.45	29	6619	620	1739513
Subclavian vein thrombosis	93.48	48.45	22	6626	159	1739974
White blood cell count decreased	93.17	48.45	73	6575	13076	1727057
Erythema	92.48	48.45	75	6573	14113	1726020
Pain	92.30	48.45	99	6549	26558	1713575
Jaundice	92.05	48.45	54	6594	6008	1734125
Colitis microscopic	91.93	48.45	25	6623	341	1739792
Leukocytosis	91.80	48.45	45	6603	3488	1736645
Hypophagia	89.25	48.45	44	6604	3453	1736680
Arteriospasm coronary	88.41	48.45	28	6620	666	1739467
Hypomagnesaemia	86.99	48.45	37	6611	2061	1738072
Oedema peripheral	86.47	48.45	75	6573	15475	1724658
Carcinoembryonic antigen increased	85.26	48.45	21	6627	188	1739945
Hypersensitivity	85.02	48.45	63	6585	10381	1729752
Back pain	84.16	48.45	76	6572	16537	1723596
Blood potassium decreased	83.79	48.45	37	6611	2258	1737875
Hepatotoxicity	82.28	48.45	40	6608	3044	1737089
Foetal disorder	81.90	48.45	17	6631	62	1740071
Peritonitis	80.60	48.45	38	6610	2701	1737432
Klebsiella infection	80.02	48.45	27	6621	788	1739345
Clostridial infection	79.65	48.45	26	6622	683	1739450
Lethargy	78.70	48.45	52	6596	7132	1733001
Inflammation	78.03	48.45	40	6608	3410	1736723
Cachexia	77.94	48.45	28	6620	988	1739145
Prothrombin level decreased	76.20	48.45	20	6628	236	1739897
Haematotoxicity	75.75	48.45	27	6621	931	1739202
Abdominal pain upper	75.59	48.45	60	6588	10941	1729192
Oral pain	75.55	48.45	30	6618	1400	1738733
Dysphagia	75.36	48.45	58	6590	10110	1730023
Coagulopathy	73.97	48.45	36	6612	2745	1737388
Blood lactic acid increased	73.60	48.45	26	6622	873	1739260
Induration	73.52	48.45	19	6629	210	1739923
Gastrointestinal perforation	73.38	48.45	25	6623	752	1739381
Syncope	72.09	48.45	65	6583	14104	1726029
Neutropenia neonatal	71.99	48.45	14	6634	33	1740100
Bacteraemia	70.86	48.45	31	6617	1849	1738284
Hepatic failure	67.75	48.45	44	6604	5859	1734274
Large intestine perforation	66.66	48.45	26	6622	1156	1738977
Febrile infection	66.62	48.45	17	6631	178	1739955
Neoplasm recurrence	66.55	48.45	20	6628	397	1739736
Liver abscess	66.30	48.45	22	6626	609	1739524
Hyperglycaemia	65.49	48.45	41	6607	5124	1735009
Atrial fibrillation	64.72	48.45	63	6585	15048	1725085
Posterior reversible encephalopathy syndrome	64.43	48.45	27	6621	1448	1738685
Abdominal distension	64.24	48.45	44	6604	6400	1733733
Aspartate aminotransferase increased	64.08	48.45	54	6594	10702	1729431
Candida infection	63.30	48.45	29	6619	1929	1738204
Mouth ulceration	63.11	48.45	28	6620	1727	1738406
Rash pustular	63.11	48.45	25	6623	1159	1738974
Dry mouth	62.40	48.45	36	6612	3877	1736256
Organising pneumonia	62.37	48.45	23	6625	875	1739258
Haematochezia	62.15	48.45	39	6609	4893	1735240
Vena cava thrombosis	61.83	48.45	17	6631	242	1739891
Loss of consciousness	61.81	48.45	61	6587	14814	1725319
Adenocarcinoma of colon	60.71	48.45	19	6629	434	1739699
Systemic inflammatory response syndrome	59.99	48.45	22	6626	824	1739309
Venous thrombosis	59.90	48.45	21	6627	689	1739444
Alanine aminotransferase increased	59.85	48.45	55	6593	12223	1727910
Toxicity to various agents	59.61	48.45	83	6565	29058	1711075
Hyperammonaemic encephalopathy	59.57	48.45	18	6630	364	1739769
Angina pectoris	59.05	48.45	38	6610	4980	1735153
Fall	57.89	48.45	79	6569	27135	1712998
Blood alkaline phosphatase increased	57.84	48.45	38	6610	5157	1734976
Haematocrit decreased	56.90	48.45	35	6613	4238	1735895
Neutrophilia	56.19	48.45	19	6629	558	1739575
Thrombosis	55.92	48.45	43	6605	7478	1732655
Tenderness	55.88	48.45	22	6626	1003	1739130
Conjunctivitis	55.41	48.45	25	6623	1604	1738529
Low birth weight baby	55.34	48.45	21	6627	866	1739267
Acute coronary syndrome	55.26	48.45	28	6620	2327	1737806
Premature baby	54.88	48.45	30	6618	2912	1737221
Platelet count decreased	54.70	48.45	60	6588	16463	1723670
Rectal haemorrhage	53.25	48.45	37	6611	5505	1734628
Metastases to peritoneum	52.84	48.45	16	6632	326	1739807
Large intestinal obstruction	52.64	48.45	15	6633	245	1739888
Muscular weakness	52.07	48.45	47	6601	10202	1729931
Dyspepsia	51.96	48.45	35	6613	4950	1735183
Recall phenomenon	51.66	48.45	13	6635	128	1740005
Hyperammonaemia	51.36	48.45	21	6627	1057	1739076
Abscess	51.32	48.45	25	6623	1909	1738224
Pancreatic carcinoma metastatic	51.30	48.45	18	6630	592	1739541
Embolism	50.64	48.45	21	6627	1096	1739037
Malnutrition	50.42	48.45	23	6625	1514	1738619
Pneumatosis intestinalis	50.09	48.45	17	6631	505	1739628
Perihepatic abscess	49.98	48.45	9	6639	11	1740122
Rectal abscess	49.81	48.45	14	6634	217	1739916
Endocarditis	49.62	48.45	20	6628	970	1739163
Dysphonia	49.59	48.45	30	6618	3525	1736608
Stoma site pain	49.55	48.45	11	6637	59	1740074
Gastrointestinal inflammation	49.46	48.45	17	6631	525	1739608
Flushing	49.10	48.45	37	6611	6242	1733891
Cough	49.01	48.45	61	6587	19136	1720997
Oesophageal haemorrhage	48.94	48.45	14	6634	232	1739901
Hypoxia	48.55	48.45	36	6612	5927	1734206

Pharmacologic Action:

Source	Code	Description
ATC	V03AF03	VARIOUS ALL OTHER THERAPEUTIC PRODUCTS ALL OTHER THERAPEUTIC PRODUCTS Detoxifying agents for antineoplastic treatment
ATC	V03AF06	VARIOUS ALL OTHER THERAPEUTIC PRODUCTS ALL OTHER THERAPEUTIC PRODUCTS Detoxifying agents for antineoplastic treatment
FDA EPC	N0000178369	Folate Analog
FDA CS	M0008658	Folic Acid
MeSH PA	D000931	Antidotes
MeSH PA	D018977	Micronutrients
MeSH PA	D020011	Protective Agents
MeSH PA	D014803	Vitamin B Complex
MeSH PA	D014815	Vitamins

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Megaloblastic anemia	indication	53165003	DOID:13382
Folic acid deficiency	indication	190633005
Bone Marrow Suppression due to Folic Acid Antagonism	indication
Methotrexate Toxicity	indication
Trimethoprim Toxicity	indication
Trimetrexate Toxicity	indication
Sulfadiazine Toxicity	indication
Pyrimethamine Toxicity	indication
Adjunct to Fluorouracil Treatment of Colorectal Cancer	indication
Pernicious anemia	contraindication	84027009	DOID:13381
Cobalamin deficiency	contraindication	190634004

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.61	acidic
pKa2	5.29	acidic
pKa3	10.26	acidic
pKa4	12.96	acidic
pKa5	4.59	Basic
pKa6	2.23	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	4.07		WOMBAT-PK
Dihydrofolate reductase	Enzyme	P00374	DYR_HUMAN		Ki	5.63		CHEMBL

External reference:

ID	Source
D002955	MESH_DESCRIPTOR_UI
4019798	VUID
N0000147887	NUI
C0023413	UMLSCUI
D01211	KEGG_DRUG
1528001	SNOMEDCT_US
396065004	SNOMEDCT_US
6313	RXNORM
d00275	MMSL
4019798	VANDF
001050	NDDF
DB00650	DRUGBANK_ID
CHEMBL1679	ChEMBL_ID
Q573I9DVLP	UNII
690	INN_ID
1492-18-8	SECONDARY_CAS_RN
CHEBI:31340	CHEBI
CHEMBL1201138	ChEMBL_ID
CHEMBL1232801	ChEMBL_ID
CHEMBL3707260	ChEMBL_ID
135403648	PUBCHEM_CID
4816	IUPHAR_LIGAND_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4496	TABLET	5 mg	ORAL	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4497	TABLET	10 mg	ORAL	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4498	TABLET	15 mg	ORAL	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4499	TABLET	25 mg	ORAL	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-8496	TABLET	5 mg	ORAL	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9368	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9552	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9553	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9554	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9555	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0555-0484	TABLET	5 mg	ORAL	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0555-0485	TABLET	25 mg	ORAL	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5140	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5145	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6703	TABLET	25 mg	ORAL	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-813	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-814	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-815	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAVENOUS	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-816	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAVENOUS	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-828	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	ANDA	12 sections
LEUCOVORIN CALCIUM	HUMAN PRESCRIPTION DRUG LABEL	1	50742-464	INJECTION, SOLUTION	10 mg	INTRAMUSCULAR	ANDA	12 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	51079-581	TABLET	5 mg	ORAL	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	51079-582	TABLET	25 mg	ORAL	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	54868-3310	TABLET	5 mg	ORAL	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5915	TABLET	15 mg	ORAL	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	60687-227	TABLET	25 mg	ORAL	ANDA	13 sections
Leucovorin calcium	HUMAN PRESCRIPTION DRUG LABEL	1	63323-631	INJECTION	10 mg	INTRAVENOUS	ANDA	11 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	63323-710	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAMUSCULAR	ANDA	13 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	63323-711	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAMUSCULAR	ANDA	13 sections
EnBrace HR	HUMAN PRESCRIPTION DRUG LABEL	5	64661-650	CAPSULE, DELAYED RELEASE PELLETS	2.50 mg	ORAL	UNAPPROVED DRUG OTHER	12 sections