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

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	975.88	11.53	1003	54474	158182	53135407
Mucosal inflammation	510.94	11.53	394	55083	42390	53251199
Neuropathy peripheral	496.17	11.53	573	54904	102614	53190975
Neurotoxicity	459.80	11.53	252	55225	15097	53278492
Thrombocytopenia	408.52	11.53	605	54872	138122	53155467
Diarrhoea	331.08	11.53	1403	54074	624143	52669446
Disease progression	301.94	11.53	446	55031	101474	53192115
Febrile neutropenia	287.82	11.53	443	55034	104493	53189096
Skin toxicity	245.60	11.53	108	55369	3985	53289604
Colorectal cancer metastatic	206.93	11.53	63	55414	784	53292805
Polyneuropathy	189.45	11.53	136	55341	13097	53280492
Leukopenia	184.48	11.53	298	55179	73165	53220424
Stomatitis	183.91	11.53	350	55127	97808	53195781
Dermatitis acneiform	178.45	11.53	89	55388	4381	53289208
Haematotoxicity	170.88	11.53	105	55372	7792	53285797
Vomiting	161.19	11.53	973	54504	496166	52797423
Posterior reversible encephalopathy syndrome	152.89	11.53	130	55347	16030	53277559
Palmar-plantar erythrodysaesthesia syndrome	138.73	11.53	140	55337	21466	53272123
Pancytopenia	135.57	11.53	295	55182	90633	53202956
Pulmonary embolism	124.96	11.53	329	55148	114113	53179476
Metastases to liver	123.10	11.53	131	55346	21365	53272224
Nausea	116.81	11.53	1248	54229	754843	52538746
Malignant neoplasm progression	113.40	11.53	238	55239	71303	53222286
Bone marrow failure	113.29	11.53	148	55329	29967	53263622
Anaemia	111.55	11.53	575	54902	276143	53017446
Systemic lupus erythematosus	109.25	11.53	5	55472	125409	53168180
Abdominal pain	106.09	11.53	536	54941	255367	53038222
Arteriospasm coronary	104.82	11.53	59	55418	3718	53289871
Gastrointestinal toxicity	104.77	11.53	64	55413	4698	53288891
Enteritis	103.09	11.53	75	55402	7371	53286218
Product dose omission issue	100.20	11.53	37	55440	191583	53102006
Focal nodular hyperplasia	85.96	11.53	29	55448	511	53293078
Drug clearance decreased	83.92	11.53	35	55442	1131	53292458
Peripheral swelling	82.06	11.53	57	55420	206051	53087538
Gastrointestinal perforation	80.51	11.53	48	55429	3371	53290218
Proteinuria	77.80	11.53	95	55382	17973	53275616
Dehydration	77.03	11.53	363	55114	168047	53125542
Adenocarcinoma of colon	76.93	11.53	41	55436	2318	53291271
Glossodynia	75.83	11.53	8	55469	100283	53193306
Laryngospasm	73.61	11.53	43	55434	2907	53290682
Myelosuppression	73.12	11.53	78	55399	12750	53280839
Hypomagnesaemia	72.49	11.53	108	55369	24703	53268886
Leukoencephalopathy	71.19	11.53	48	55429	4176	53289413
Hyperammonaemic encephalopathy	70.72	11.53	37	55440	2014	53291575
Dysarthria	70.21	11.53	140	55337	40428	53253161
Non-cirrhotic portal hypertension	69.78	11.53	18	55459	115	53293474
Arthropathy	69.52	11.53	30	55447	141423	53152166
Portal hypertension	69.22	11.53	45	55432	3683	53289906
General physical health deterioration	68.85	11.53	319	55158	146623	53146966
Peripheral sensory neuropathy	66.57	11.53	57	55420	7091	53286498
Metastases to lung	66.42	11.53	71	55406	11633	53281956
Swelling	63.52	11.53	63	55414	191042	53102547
Hyperammonaemia	62.65	11.53	48	55429	5101	53288488
Fall	62.05	11.53	180	55297	358260	52935329
Pyrexia	60.17	11.53	662	54815	402531	52891058
Paronychia	59.63	11.53	46	55431	4938	53288651
Colon cancer metastatic	58.95	11.53	28	55449	1237	53292352
Insomnia	58.43	11.53	65	55412	187007	53106582
Intestinal perforation	57.58	11.53	65	55412	11315	53282274
Hypertension	57.32	11.53	416	55061	225015	53068574
Human bocavirus infection	56.89	11.53	19	55458	324	53293265
Secondary immunodeficiency	56.03	11.53	26	55451	1089	53292500
Drug hypersensitivity	54.52	11.53	122	55355	265120	53028469
Pneumatosis intestinalis	54.10	11.53	32	55445	2214	53291375
Hospitalisation	52.83	11.53	6	55471	71006	53222583
Splenomegaly	51.76	11.53	59	55418	10380	53283209
Ileus	50.88	11.53	70	55407	14885	53278704
Pain	50.87	11.53	381	55096	588017	52705572
Drug abuse	50.12	11.53	5	55472	65521	53228068
Hand deformity	48.51	11.53	14	55463	84835	53208754
Suicide attempt	48.51	11.53	3	55474	58165	53235424
Loss of employment	48.28	11.53	26	55451	1501	53292088
Synovitis	48.25	11.53	26	55451	107867	53185722
Drug ineffective	48.16	11.53	582	54895	816663	52476926
Neoplasm progression	47.91	11.53	100	55377	29819	53263770
Hypokalaemia	47.76	11.53	213	55264	96304	53197285
Abdominal discomfort	46.79	11.53	100	55377	220962	53072627
Depression	42.88	11.53	78	55399	182974	53110615
Trichomegaly	42.85	11.53	10	55467	39	53293550
Metastases to meninges	42.63	11.53	27	55450	2112	53291477
Gene mutation	41.00	11.53	22	55455	1261	53292328
Asthma	40.92	11.53	32	55445	108940	53184649
Ascites	40.05	11.53	111	55366	39624	53253965
Hepatic enzyme increased	39.22	11.53	44	55433	126151	53167438
Enterobacter infection	39.07	11.53	25	55452	1991	53291598
Cystitis radiation	39.02	11.53	10	55467	62	53293527
Joint swelling	38.98	11.53	120	55357	234518	53059071
Cholangitis	38.79	11.53	36	55441	4977	53288612
Steatohepatitis	38.48	11.53	16	55461	513	53293076
Stress cardiomyopathy	38.46	11.53	46	55431	8516	53285073
Venous pressure jugular decreased	38.38	11.53	9	55468	36	53293553
Contraindicated product administered	38.23	11.53	51	55426	135578	53158011
Atypical haemolytic uraemic syndrome	38.13	11.53	16	55461	525	53293064
Pericarditis	37.99	11.53	10	55467	64396	53229193
Sepsis	37.62	11.53	271	55206	146158	53147431
Mucosal toxicity	37.50	11.53	14	55463	335	53293254
Bladder tamponade	37.26	11.53	10	55467	76	53293513
Short-bowel syndrome	37.10	11.53	15	55462	447	53293142
Dizziness	37.07	11.53	231	55246	372028	52921561
Neoplasm recurrence	36.91	11.53	26	55451	2428	53291161
Wound	36.82	11.53	25	55452	91532	53202057
Device related infection	36.30	11.53	76	55401	22710	53270879
Injury	36.22	11.53	5	55472	50966	53242623
Therapy partial responder	36.05	11.53	38	55439	6125	53287464
Neuromyotonia	35.66	11.53	9	55468	52	53293537
Hepatocellular injury	35.56	11.53	89	55388	29897	53263692
Pain in extremity	35.51	11.53	164	55313	284886	53008703
Factor VII deficiency	35.41	11.53	8	55469	26	53293563
Neutrophil count decreased	35.38	11.53	122	55355	48976	53244613
Gastroenteritis norovirus	35.28	11.53	22	55455	1675	53291914
Lower respiratory tract infection	35.07	11.53	26	55451	90955	53202634
Female genital tract fistula	35.05	11.53	31	55446	4027	53289562
Venous thrombosis	34.97	11.53	34	55443	4980	53288609
Embolism	34.84	11.53	41	55436	7462	53286127
Chills	34.82	11.53	207	55270	104641	53188948
Leukoerythroblastosis	34.53	11.53	12	55465	232	53293357
Irritable bowel syndrome	34.24	11.53	3	55474	43629	53249960
Cardiotoxicity	34.08	11.53	40	55437	7259	53286330
Colorectal cancer	33.97	11.53	20	55457	1372	53292217
Weight increased	33.70	11.53	105	55372	204462	53089127
Vena cava thrombosis	33.67	11.53	24	55453	2284	53291305
Discomfort	33.42	11.53	30	55447	95442	53198147
Immune thrombocytopenia	33.35	11.53	45	55432	9393	53284196
Aortic thrombosis	32.85	11.53	18	55459	1076	53292513
Off label use	32.75	11.53	680	54797	471532	52822057
Large intestine perforation	32.67	11.53	41	55436	7973	53285616
Sinusitis	32.62	11.53	80	55397	168484	53125105
Thrombocytopenic purpura	32.53	11.53	19	55458	1284	53292305
Herpes simplex	32.24	11.53	40	55437	7689	53285900
Epistaxis	32.01	11.53	149	55328	68561	53225028
Carcinoembryonic antigen increased	31.90	11.53	20	55457	1537	53292052
Interstitial lung disease	31.76	11.53	133	55344	58489	53235100
Blood cholesterol increased	31.69	11.53	8	55469	52981	53240608
Septic shock	31.27	11.53	138	55339	62091	53231498
Plasma cell myeloma	31.11	11.53	6	55471	47868	53245721
Nicotinic acid deficiency	30.89	11.53	8	55469	52	53293537
Hypersensitivity vasculitis	30.75	11.53	30	55447	4413	53289176
Intestinal obstruction	30.67	11.53	82	55395	28659	53264930
Arthralgia	30.64	11.53	301	55176	439482	52854107
Injection site pain	30.59	11.53	44	55433	113347	53180242
Haemolytic anaemia	29.86	11.53	45	55432	10394	53283195
Psoriasis	29.73	11.53	28	55449	87061	53206528
Sleep disorder	29.69	11.53	12	55465	58858	53234731
Cholinergic syndrome	28.91	11.53	12	55465	383	53293206
Tumour lysis syndrome	28.52	11.53	38	55439	7836	53285753
Chronic obstructive pulmonary disease	28.36	11.53	14	55463	61059	53232530
Rash pustular	28.20	11.53	36	55441	7120	53286469
Suicidal ideation	27.91	11.53	14	55463	60497	53233092
Rheumatoid arthritis	27.87	11.53	202	55275	314329	52979260
Electrocardiogram QT prolonged	27.63	11.53	12	55465	56391	53237198
Fluid retention	27.58	11.53	11	55466	54390	53239199
Wrong technique in product usage process	27.52	11.53	14	55463	60018	53233571
Anastomotic leak	27.15	11.53	12	55465	448	53293141
Small intestinal obstruction	27.09	11.53	57	55420	17090	53276499
Myelodysplastic syndrome	27.04	11.53	56	55421	16604	53276985
Nasal septum perforation	26.66	11.53	14	55463	768	53292821
Headache	26.50	11.53	396	55081	536425	52757164
Superior vena cava syndrome	26.21	11.53	13	55464	632	53292957
Memory impairment	25.84	11.53	30	55447	84727	53208862
Metastases to lymph nodes	25.57	11.53	35	55442	7405	53286184
Catabolic state	25.55	11.53	7	55470	58	53293531
Ocular toxicity	25.48	11.53	12	55465	520	53293069
Aortic intramural haematoma	25.44	11.53	7	55470	59	53293530
Peritonitis	25.32	11.53	64	55413	21623	53271966
Contusion	25.19	11.53	48	55429	110684	53182905
Helicobacter infection	25.16	11.53	5	55472	39064	53254525
Encapsulating peritoneal sclerosis	25.16	11.53	11	55466	400	53293189
Cardiomyopathy	24.92	11.53	55	55422	17033	53276556
Gait disturbance	24.44	11.53	84	55393	158758	53134831
Myalgia	23.79	11.53	66	55411	133425	53160164
Meningitis streptococcal	23.76	11.53	8	55469	140	53293449
Duodenal ulcer perforation	23.74	11.53	4	55473	35179	53258410
Hemiparesis	23.66	11.53	62	55415	21413	53272176
ECG signs of myocardial ischaemia	23.61	11.53	7	55470	79	53293510
Myeloid leukaemia	23.53	11.53	10	55467	339	53293250
Throat tightness	23.32	11.53	63	55414	22153	53271436
Large intestinal obstruction	23.06	11.53	18	55459	1965	53291624
Paraesthesia	23.05	11.53	218	55259	127297	53166292
Rhinovirus infection	22.91	11.53	24	55453	3841	53289748
Migraine	22.90	11.53	30	55447	80387	53213202
Jugular vein thrombosis	22.86	11.53	21	55456	2865	53290724
Neutropenic colitis	22.78	11.53	20	55457	2573	53291016
Clostridium difficile colitis	22.74	11.53	58	55419	19707	53273882
Feeling abnormal	22.58	11.53	69	55408	135232	53158357
Respiratory symptom	22.41	11.53	20	55457	2629	53290960
Second primary malignancy	22.21	11.53	32	55445	7100	53286489
Mobility decreased	22.18	11.53	28	55449	76243	53217346
Portal vein dilatation	21.96	11.53	5	55472	17	53293572
K-ras gene mutation	21.96	11.53	5	55472	17	53293572
Encephalopathy	21.92	11.53	86	55391	36722	53256867
Inferior vena cava stenosis	21.74	11.53	5	55472	18	53293571
Anxiety	21.70	11.53	118	55359	196586	53097003
Tumour perforation	21.55	11.53	7	55470	109	53293480
Acute promyelocytic leukaemia	21.53	11.53	13	55464	934	53292655
Gastrointestinal stoma complication	21.39	11.53	16	55461	1640	53291949
Venoocclusive liver disease	21.25	11.53	25	55452	4547	53289042
Abortion spontaneous	21.19	11.53	11	55466	46624	53246965
Subileus	20.93	11.53	21	55456	3195	53290394
Multiple-drug resistance	20.83	11.53	21	55456	3214	53290375
Biliary tract infection	20.68	11.53	10	55467	460	53293129
Hypertrichosis	20.64	11.53	13	55464	1007	53292582
Intentional product misuse	20.51	11.53	13	55464	49379	53244210
Cholestasis	20.40	11.53	71	55406	28624	53264965
Overdose	20.15	11.53	52	55425	107684	53185905
Crystal nephropathy	20.04	11.53	12	55465	849	53292740
Proctalgia	19.86	11.53	26	55451	5270	53288319
No adverse event	19.80	11.53	8	55469	39257	53254332
Cutaneous tuberculosis	19.78	11.53	7	55470	143	53293446
Productive cough	19.64	11.53	18	55459	56711	53236878
Hypocapnia	19.53	11.53	9	55468	371	53293218
Drug withdrawal syndrome	19.33	11.53	3	55474	28019	53265570
Human herpesvirus 6 infection	19.25	11.53	18	55459	2512	53291077
Depilation	19.09	11.53	4	55473	8	53293581
Rectal cancer recurrent	18.99	11.53	5	55472	35	53293554
Petechiae	18.96	11.53	43	55434	13562	53280027
Pruritus	18.83	11.53	205	55272	293627	52999962
Portal shunt	18.77	11.53	4	55473	9	53293580
Deep vein thrombosis	18.77	11.53	149	55328	82764	53210825
Venous thrombosis limb	18.76	11.53	19	55458	2924	53290665
Red cell fragmentation syndrome	18.75	11.53	5	55472	37	53293552
Hallucination	18.74	11.53	17	55460	53821	53239768
Occult blood	18.58	11.53	13	55464	1201	53292388
Multiple organ dysfunction syndrome	18.52	11.53	110	55367	55567	53238022
Soft tissue necrosis	18.49	11.53	9	55468	420	53293169
Upper respiratory tract infection	18.44	11.53	27	55450	69070	53224519
Pneumothorax	18.35	11.53	46	55431	15461	53278128
Subacute cutaneous lupus erythematosus	18.31	11.53	17	55460	2351	53291238
Tumour necrosis	18.29	11.53	11	55466	785	53292804
Metastases to peritoneum	18.27	11.53	19	55458	3016	53290573
Ovarian fibroma	18.26	11.53	6	55471	97	53293492
Vitiligo	18.25	11.53	13	55464	1236	53292353
Coronary artery disease	18.24	11.53	6	55471	33431	53260158
Blood pressure fluctuation	18.07	11.53	79	55398	35391	53258198
Unevaluable event	17.99	11.53	15	55462	49483	53244106
Endometrial dysplasia	17.95	11.53	4	55473	12	53293577
Maternal exposure during pregnancy	17.92	11.53	92	55385	155547	53138042
Irritability	17.88	11.53	5	55472	30948	53262641
Hyperbilirubinaemia	17.72	11.53	37	55440	11032	53282557
Evans syndrome	17.59	11.53	7	55470	200	53293389
Pneumonia	17.51	11.53	308	55169	406861	52886728
Adverse drug reaction	17.42	11.53	18	55459	53607	53239982
Amnesia	17.37	11.53	13	55464	45275	53248314
Somnolence	17.21	11.53	103	55374	167631	53125958
Condition aggravated	17.21	11.53	212	55265	296922	52996667
Haemolytic uraemic syndrome	17.18	11.53	17	55460	2544	53291045
Peripheral sensorimotor neuropathy	17.13	11.53	13	55464	1362	53292227
Pelvic fluid collection	17.10	11.53	11	55466	884	53292705
Hip arthroplasty	17.06	11.53	4	55473	27858	53265731
Mouth ulceration	17.04	11.53	68	55409	29258	53264331
Reticulocytosis	16.94	11.53	6	55471	123	53293466
Cardiomyopathy acute	16.93	11.53	7	55470	221	53293368
Cardiac arrest	16.92	11.53	46	55431	93621	53199968
Gastroenteropancreatic neuroendocrine tumour disease	16.90	11.53	5	55472	56	53293533
Asthenia	16.83	11.53	472	55005	343118	52950471
Exposure during pregnancy	16.63	11.53	70	55407	124790	53168799
Product quality issue	16.43	11.53	9	55468	37014	53256575
Depressed mood	16.38	11.53	9	55468	36955	53256634
Dysaesthesia pharynx	16.17	11.53	6	55471	141	53293448
Loss of personal independence in daily activities	16.10	11.53	30	55447	69785	53223804
Hepatitis toxic	15.99	11.53	18	55459	3123	53290466
Bradycardia	15.98	11.53	31	55446	71025	53222564
Intracranial pressure increased	15.96	11.53	22	55455	4684	53288905
Psychotic disorder	15.96	11.53	3	55474	24382	53269207
Pelvic abscess	15.86	11.53	13	55464	1523	53292066
Emotional distress	15.63	11.53	7	55470	32310	53261279
Dysphagia	15.60	11.53	145	55332	84252	53209337
Agitation	15.56	11.53	23	55454	58603	53234986
Liver abscess	15.54	11.53	17	55460	2858	53290731
Pneumothorax spontaneous	15.53	11.53	9	55468	599	53292990
Percussion test abnormal	15.53	11.53	3	55474	3	53293586
Bone pain	15.40	11.53	18	55459	50704	53242885
Treatment failure	15.30	11.53	75	55402	128328	53165261
Rectal perforation	15.18	11.53	8	55469	442	53293147
Folliculitis	15.13	11.53	7	55470	31702	53261887
Colitis	15.06	11.53	84	55393	41468	53252121
Sedation	15.04	11.53	6	55471	29669	53263920
Hydronephrosis	15.03	11.53	31	55446	9165	53284424
Gastrointestinal anastomotic leak	14.99	11.53	6	55471	174	53293415
COVID-19	14.92	11.53	10	55467	36878	53256711
Varices oesophageal	14.89	11.53	17	55460	2995	53290594
Toxic encephalopathy	14.79	11.53	24	55453	5903	53287686
Product prescribing error	14.72	11.53	3	55474	23028	53270561
Product use in unapproved indication	14.70	11.53	180	55297	112109	53181480
Nodular regenerative hyperplasia	14.68	11.53	7	55470	312	53293277
Rhinocerebral mucormycosis	14.65	11.53	6	55471	185	53293404
Product intolerance	14.62	11.53	4	55473	33	53293556
Hepatic vein stenosis	14.51	11.53	4	55473	34	53293555
Haemolysis	14.47	11.53	25	55452	6471	53287118
Blood creatine phosphokinase increased	14.46	11.53	6	55471	28979	53264610
Metastasis	14.40	11.53	21	55456	4710	53288879
Optic disc hyperaemia	14.32	11.53	3	55474	6	53293583
Periportal sinus dilatation	14.32	11.53	3	55474	6	53293583
Laryngeal injury	14.32	11.53	3	55474	6	53293583
Type II hypersensitivity	14.32	11.53	3	55474	6	53293583
Pelvic mass	14.25	11.53	11	55466	1182	53292407
Overgrowth fungal	14.14	11.53	5	55472	102	53293487
Procedural site reaction	14.08	11.53	7	55470	342	53293247
Blister	13.98	11.53	39	55438	78714	53214875
Tubular breast carcinoma	13.75	11.53	4	55473	42	53293547
Knee arthroplasty	13.72	11.53	9	55468	33560	53260029
Chemotherapeutic drug level above therapeutic	13.67	11.53	4	55473	43	53293546
Peritoneal disorder	13.64	11.53	8	55469	545	53293044
Escherichia bacteraemia	13.60	11.53	17	55460	3291	53290298
Fluid overload	13.51	11.53	6	55471	27825	53265764
Acquired gene mutation	13.50	11.53	9	55468	768	53292821
Optic nerve disorder	13.50	11.53	9	55468	768	53292821
Cough	13.50	11.53	187	55290	256706	53036883
Cognitive disorder	13.48	11.53	16	55461	44762	53248827
Head injury	13.46	11.53	5	55472	25828	53267761
Gait inability	13.45	11.53	12	55465	38299	53255290
Disease recurrence	13.34	11.53	50	55427	20896	53272693
Colon cancer recurrent	13.27	11.53	4	55473	48	53293541
Panic attack	13.26	11.53	3	55474	21415	53272174
Duodenal obstruction	13.19	11.53	6	55471	240	53293349
Balance disorder	13.18	11.53	36	55441	73171	53220418
Hepatic lesion	13.18	11.53	19	55458	4218	53289371
Extravasation	13.16	11.53	14	55463	2280	53291309
Tumour rupture	13.15	11.53	5	55472	126	53293463
Cachexia	13.01	11.53	21	55456	5143	53288446
Acute myeloid leukaemia	13.01	11.53	43	55434	16889	53276700
Fibromyalgia	13.00	11.53	16	55461	44059	53249530
Psychiatric decompensation	12.97	11.53	11	55466	1351	53292238
Bronchitis	12.96	11.53	66	55411	111833	53181756
Neutropenic sepsis	12.90	11.53	39	55438	14610	53278979
Benign hydatidiform mole	12.90	11.53	5	55472	133	53293456
Drug eruption	12.84	11.53	5	55472	25089	53268500
Cytopenia	12.79	11.53	29	55448	9141	53284448
Accessory spleen	12.79	11.53	3	55474	12	53293577
Impaired healing	12.78	11.53	30	55447	64175	53229414
Acute kidney injury	12.76	11.53	350	55127	253518	53040071
Febrile bone marrow aplasia	12.66	11.53	25	55452	7164	53286425
Confusional state	12.63	11.53	135	55342	194086	53099503
Diabetes mellitus	12.57	11.53	23	55454	53876	53239713
Vaginal fistula	12.54	11.53	7	55470	434	53293155
Hypertransaminasaemia	12.48	11.53	18	55459	3998	53289591
Granulomatous lymphadenitis	12.46	11.53	5	55472	146	53293443
Tubal rupture	12.42	11.53	3	55474	14	53293575
Peripheral nerve injury	12.39	11.53	7	55470	444	53293145
Cardiac failure congestive	12.35	11.53	52	55425	92705	53200884
Neuroborreliosis	12.33	11.53	4	55473	62	53293527
Hepatic steatosis	12.26	11.53	57	55420	26202	53267387
Anaemia of malignant disease	12.25	11.53	7	55470	454	53293135
Eczema asteatotic	12.21	11.53	6	55471	286	53293303
Cerebrovascular accident	12.20	11.53	62	55415	105112	53188477
Neuroendocrine carcinoma of the skin	12.11	11.53	7	55470	464	53293125
Haematuria	12.08	11.53	60	55417	28329	53265260
Treatment noncompliance	12.02	11.53	10	55467	33025	53260564
Hemianaesthesia	12.00	11.53	7	55470	472	53293117
Ovarian cystectomy	11.89	11.53	5	55472	165	53293424
Gastrooesophageal reflux disease	11.85	11.53	45	55432	82618	53210971
Enterocolitis	11.79	11.53	24	55453	7028	53286561
Hypocalcaemia	11.78	11.53	61	55416	29276	53264313
Gastrointestinal necrosis	11.76	11.53	15	55462	2965	53290624
Metastases to bone marrow	11.69	11.53	6	55471	314	53293275
Portal vein thrombosis	11.65	11.53	14	55463	2605	53290984
Acute lymphocytic leukaemia recurrent	11.64	11.53	13	55464	2235	53291354
Visual acuity reduced transiently	11.61	11.53	5	55472	175	53293414
Device dislocation	11.59	11.53	5	55472	23592	53269997
Respiratory disorder	11.59	11.53	11	55466	34086	53259503
Mitral valve disease	11.59	11.53	13	55464	2247	53291342
Organising pneumonia	11.58	11.53	20	55457	5176	53288413
Finger deformity	11.55	11.53	21	55456	5656	53287933

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
Neutropenia	947.22	12.73	1274	62558	140901	32308793
Neuropathy peripheral	576.60	12.73	732	63100	76250	32373444
Diarrhoea	539.10	12.73	1751	62081	363051	32086643
Skin toxicity	515.09	12.73	215	63617	3591	32446103
Mucosal inflammation	463.89	12.73	440	63392	32994	32416700
Disease progression	396.12	12.73	653	63179	86209	32363485
Neurotoxicity	361.48	12.73	272	63560	14798	32434896
Metastases to liver	347.57	12.73	250	63582	12682	32437012
Dermatitis acneiform	337.96	12.73	186	63646	5859	32443835
Stomatitis	307.76	12.73	387	63445	39842	32409852
Thrombocytopenia	306.93	12.73	805	63027	147494	32302200
Palmar-plantar erythrodysaesthesia syndrome	305.91	12.73	251	63581	15498	32434196
Colorectal cancer metastatic	269.06	12.73	96	63736	1021	32448673
Arteriospasm coronary	259.31	12.73	122	63710	2738	32446956
Polyneuropathy	206.53	12.73	186	63646	13029	32436665
Febrile neutropenia	158.12	12.73	555	63277	119011	32330683
Proteinuria	155.52	12.73	181	63651	17174	32432520
Completed suicide	155.41	12.73	6	63826	92511	32357183
Gastrointestinal toxicity	150.21	12.73	77	63755	2092	32447602
Leukopenia	144.55	12.73	346	63486	59776	32389918
Skin reaction	143.97	12.73	100	63732	4792	32444902
Vomiting	142.92	12.73	869	62963	234688	32215006
Cardiotoxicity	133.97	12.73	96	63736	4836	32444858
Product dose omission issue	130.92	12.73	22	63810	102553	32347141
Nausea	130.53	12.73	1074	62758	319775	32129919
Portal hypertension	126.50	12.73	86	63746	3978	32445716
Paronychia	126.49	12.73	79	63753	3158	32446536
Pyrexia	123.19	12.73	1058	62774	318910	32130784
Drug ineffective	122.62	12.73	368	63464	383109	32066585
Abdominal pain	121.06	12.73	597	63235	148932	32300762
Peripheral sensory neuropathy	118.51	12.73	100	63732	6414	32443280
Carcinoembryonic antigen increased	117.87	12.73	47	63785	693	32449001
Metastases to lung	117.01	12.73	111	63721	8306	32441388
Decreased appetite	114.19	12.73	619	63213	160194	32289500
Intestinal obstruction	112.02	12.73	169	63663	20629	32429065
Bone marrow failure	111.52	12.73	208	63624	30196	32419498
Haematotoxicity	107.09	12.73	96	63736	6680	32443014
General physical health deterioration	102.51	12.73	473	63359	114786	32334908
Drug abuse	100.64	12.73	18	63814	80225	32369469
Cardiac failure congestive	100.21	12.73	22	63810	84830	32364864
Hyperammonaemic encephalopathy	97.59	12.73	57	63775	2014	32447680
Chills	97.57	12.73	356	63476	77728	32371966
Pulmonary embolism	95.89	12.73	371	63461	83288	32366406
Hyperammonaemia	93.21	12.73	84	63748	5885	32443809
Colorectal cancer	93.15	12.73	57	63775	2196	32447498
Plasma cell myeloma	92.61	12.73	5	63827	57609	32392085
Rash pustular	89.83	12.73	78	63754	5201	32444493
Alopecia	87.77	12.73	151	63681	20579	32429115
Rhabdomyolysis	86.75	12.73	14	63818	67251	32382443
Malignant neoplasm progression	81.84	12.73	338	63494	78158	32371536
Fall	81.54	12.73	164	63668	196037	32253657
Neoplasm progression	80.37	12.73	141	63691	19517	32430177
Focal nodular hyperplasia	79.80	12.73	24	63808	140	32449554
Gastrointestinal perforation	79.72	12.73	64	63768	3826	32445868
Drug interaction	79.54	12.73	196	63636	217989	32231705
Myalgia	79.49	12.73	30	63802	81200	32368494
Anxiety	76.36	12.73	47	63785	95958	32353736
Myelosuppression	74.74	12.73	103	63729	11573	32438121
Therapy partial responder	74.28	12.73	68	63764	4862	32444832
Ascites	71.68	12.73	207	63625	39984	32409710
Insomnia	70.72	12.73	56	63776	100292	32349402
Asthma	70.27	12.73	4	63828	44061	32405633
Paraesthesia	69.63	12.73	264	63568	58680	32391014
Interstitial lung disease	69.40	12.73	282	63550	64719	32384975
Adenocarcinoma of colon	66.44	12.73	55	63777	3434	32446260
Pneumonia	66.07	12.73	418	63414	354834	32094860
Death	64.22	12.73	464	63368	382053	32067641
Somnolence	63.52	12.73	66	63766	103731	32345963
Dehydration	63.47	12.73	452	63380	128506	32321188
Headache	62.64	12.73	188	63644	196009	32253685
Hypomagnesaemia	62.00	12.73	123	63709	18682	32431012
Arthralgia	60.84	12.73	125	63707	148323	32301371
Metastases to lymph nodes	60.79	12.73	58	63774	4370	32445324
Ileus	60.53	12.73	112	63720	16153	32433541
Enteritis	57.28	12.73	71	63761	7190	32442504
Hiccups	56.99	12.73	83	63749	9812	32439882
Weight increased	56.09	12.73	49	63783	83614	32366080
Metastases to peritoneum	56.04	12.73	37	63795	1629	32448065
Small intestinal obstruction	55.67	12.73	100	63732	14096	32435598
Hospitalisation	55.22	12.73	14	63818	48957	32400737
Aggression	53.55	12.73	7	63825	39382	32410312
Subclavian vein thrombosis	53.14	12.73	29	63803	897	32448797
Intentional overdose	52.87	12.73	9	63823	41592	32408102
Febrile bone marrow aplasia	52.01	12.73	73	63759	8342	32441352
Device related infection	51.71	12.73	111	63721	17822	32431872
Bradycardia	51.59	12.73	39	63793	71523	32378171
Colon cancer metastatic	51.47	12.73	36	63796	1744	32447950
Subileus	51.04	12.73	46	63786	3222	32446472
Leukoencephalopathy	50.96	12.73	51	63781	4074	32445620
Myocardial infarction	50.49	12.73	107	63725	125569	32324125
Psoriasis	50.46	12.73	14	63818	46109	32403585
Anastomotic complication	49.84	12.73	21	63811	359	32449335
Peripheral swelling	49.59	12.73	37	63795	68308	32381386
Cholangitis	49.44	12.73	71	63761	8287	32441407
Transdifferentiation of neoplasm	49.37	12.73	14	63818	64	32449630
Dizziness	49.15	12.73	228	63604	209390	32240304
Blood glucose increased	49.06	12.73	34	63798	65207	32384487
Depression	47.62	12.73	73	63759	96987	32352707
Anastomotic leak	47.42	12.73	24	63808	634	32449060
Influenza	46.69	12.73	16	63816	45998	32403696
Epistaxis	46.48	12.73	225	63607	55630	32394064
Drug clearance decreased	45.59	12.73	31	63801	1434	32448260
Colon cancer stage III	44.93	12.73	16	63816	169	32449525
Intestinal perforation	44.79	12.73	70	63762	8805	32440889
Carbohydrate antigen 19-9 increased	44.71	12.73	17	63815	219	32449475
Suicidal ideation	44.68	12.73	10	63822	38073	32411621
Chronic obstructive pulmonary disease	44.45	12.73	20	63812	48733	32400961
Febrile infection	44.25	12.73	36	63796	2193	32447501
Proteus infection	43.69	12.73	25	63807	849	32448845
Tumour lysis syndrome	43.05	12.73	91	63741	14456	32435238
Injection site pain	42.34	12.73	7	63825	33051	32416643
Electrocardiogram ST segment elevation	42.04	12.73	50	63782	4850	32444844
Pain in extremity	40.79	12.73	110	63722	118791	32330903
Tumour necrosis	40.68	12.73	27	63805	1199	32448495
Conjunctivitis	40.17	12.73	66	63766	8660	32441034
Hallucination	40.12	12.73	27	63805	52592	32397102
Coronary artery disease	39.96	12.73	24	63808	49682	32400012
Feeling abnormal	39.75	12.73	36	63796	60387	32389307
Rheumatoid arthritis	39.48	12.73	19	63813	44525	32405169
Intravascular haemolysis	39.48	12.73	19	63813	449	32449245
Nicotinic acid deficiency	39.34	12.73	12	63820	74	32449620
Hypersensitivity	39.29	12.73	220	63612	57538	32392156
Unevaluable event	39.04	12.73	9	63823	33577	32416117
Erythema	38.37	12.73	287	63545	82818	32366876
Necrotising fasciitis	38.33	12.73	42	63790	3727	32445967
Vena cava thrombosis	38.02	12.73	25	63807	1093	32448601
Anal fissure	37.85	12.73	37	63795	2872	32446822
Anal haemorrhage	37.53	12.73	32	63800	2081	32447613
Cholinergic syndrome	37.51	12.73	19	63813	503	32449191
Colon cancer recurrent	37.50	12.73	13	63819	126	32449568
Contusion	36.90	12.73	10	63822	33458	32416236
Colitis	36.77	12.73	148	63684	33803	32415891
Acute coronary syndrome	36.48	12.73	83	63749	13858	32435836
Hypoglycaemia	36.25	12.73	32	63800	54350	32395344
Overdose	35.91	12.73	73	63759	87004	32362690
Ileal perforation	35.80	12.73	21	63811	748	32448946
Intentional product misuse	35.77	12.73	13	63819	36038	32413656
Small intestinal perforation	35.60	12.73	29	63803	1770	32447924
Wheezing	35.42	12.73	14	63818	36860	32412834
Cellulitis	35.40	12.73	28	63804	50202	32399492
Memory impairment	34.77	12.73	18	63814	40461	32409233
Pneumatosis intestinalis	34.59	12.73	38	63794	3382	32446312
Administration site extravasation	34.32	12.73	18	63814	513	32449181
Treatment noncompliance	34.31	12.73	6	63826	27196	32422498
Adverse drug reaction	34.20	12.73	5	63827	25856	32423838
Splenomegaly	33.33	12.73	82	63750	14395	32435299
Pelvic abscess	33.09	12.73	22	63810	980	32448714
Enterovesical fistula	32.84	12.73	19	63813	659	32449035
Confusional state	32.72	12.73	157	63675	142958	32306736
Recall phenomenon	32.63	12.73	18	63814	569	32449125
Anaemia of malignant disease	32.49	12.73	16	63816	398	32449296
Sinusitis	31.79	12.73	16	63816	36544	32413150
Muscle spasms	31.69	12.73	56	63776	70362	32379332
Rectal cancer metastatic	31.27	12.73	14	63818	279	32449415
Rectal adenocarcinoma	31.11	12.73	20	63812	841	32448853
Fluid retention	31.09	12.73	7	63825	26543	32423151
Abdominal pain lower	31.08	12.73	62	63770	9451	32440243
Foetal disorder	30.61	12.73	19	63813	751	32448943
Hypoalbuminaemia	30.50	12.73	70	63762	11752	32437942
Neoplasm recurrence	30.38	12.73	28	63804	2019	32447675
Large intestine perforation	30.27	12.73	56	63776	8074	32441620
Blood creatine phosphokinase increased	30.02	12.73	27	63805	45449	32404245
Proctalgia	29.83	12.73	41	63791	4593	32445101
Oesophagitis	29.33	12.73	73	63759	12908	32436786
Induration	29.28	12.73	20	63812	932	32448762
Catheter site thrombosis	28.68	12.73	8	63824	34	32449660
Pancreatic carcinoma metastatic	28.61	12.73	34	63798	3295	32446399
Jugular vein thrombosis	28.58	12.73	24	63808	1528	32448166
Evans syndrome	28.54	12.73	13	63819	270	32449424
Wrong technique in product usage process	28.08	12.73	17	63815	35042	32414652
Product prescribing error	28.05	12.73	3	63829	19714	32429980
Peritoneal neoplasm	27.96	12.73	8	63824	38	32449656
Injury	27.85	12.73	5	63827	22240	32427454
Toxic erythema of chemotherapy	27.70	12.73	9	63823	70	32449624
Product use issue	27.53	12.73	38	63794	52739	32396955
Pelvic fluid collection	27.40	12.73	10	63822	114	32449580
Asthenia	27.18	12.73	630	63202	235314	32214380
Prothrombin level decreased	26.99	12.73	21	63811	1199	32448495
Circulatory collapse	26.91	12.73	97	63735	21028	32428666
Influenza like illness	26.57	12.73	10	63822	27130	32422564
Sleep apnoea syndrome	26.41	12.73	3	63829	18811	32430883
Disturbance in attention	26.37	12.73	7	63825	23746	32425948
Rectal perforation	26.04	12.73	14	63818	420	32449274
Colitis microscopic	25.94	12.73	25	63807	1907	32447787
Anal erythema	25.89	12.73	9	63823	88	32449606
Perihepatic abscess	25.89	12.73	9	63823	88	32449606
Skin fissures	25.83	12.73	35	63797	3868	32445826
Hyperbilirubinaemia	25.72	12.73	85	63747	17645	32432049
Electrocardiogram QT prolonged	25.61	12.73	24	63808	39617	32410077
Peripheral sensorimotor neuropathy	25.61	12.73	22	63810	1445	32448249
Koebner phenomenon	25.61	12.73	8	63824	54	32449640
Portal vein thrombosis	25.50	12.73	34	63798	3701	32445993
Neutropenia neonatal	25.43	12.73	16	63816	648	32449046
Anaemia	25.41	12.73	596	63236	223028	32226666
Incorrect dose administered	25.35	12.73	19	63813	35009	32414685
Cardiac disorder	25.16	12.73	27	63805	41839	32407855
Perforation	25.04	12.73	11	63821	209	32449485
Rectal cancer	24.88	12.73	27	63805	2370	32447324
Chemotherapeutic drug level increased	24.71	12.73	11	63821	216	32449478
Hypokalaemia	24.70	12.73	189	63643	54905	32394789
Large intestinal obstruction	24.68	12.73	22	63810	1519	32448175
Pneumoperitoneum	24.67	12.73	24	63808	1852	32447842
Superior vena cava syndrome	24.60	12.73	15	63817	574	32449120
Clostridial infection	24.36	12.73	33	63799	3646	32446048
Venous thrombosis	24.34	12.73	32	63800	3435	32446259
Perioral dermatitis	24.32	12.73	9	63823	107	32449587
Device related thrombosis	24.27	12.73	18	63814	956	32448738
Enterocutaneous fistula	24.24	12.73	17	63815	827	32448867
Nephrotic syndrome	24.23	12.73	48	63784	7281	32442413
Venoocclusive liver disease	24.06	12.73	48	63784	7317	32442377
Cachexia	24.03	12.73	47	63785	7062	32442632
International normalised ratio increased	23.92	12.73	37	63795	48998	32400696
Sedation	23.55	12.73	4	63828	18522	32431172
Cataract	23.52	12.73	9	63823	24174	32425520
Acute abdomen	23.50	12.73	24	63808	1964	32447730
Cerebral vasoconstriction	23.37	12.73	11	63821	247	32449447
Adenocarcinoma	23.29	12.73	23	63809	1808	32447886
Interventricular septum rupture	23.13	12.73	6	63826	18	32449676
Liver abscess	23.05	12.73	32	63800	3619	32446075
Nail disorder	23.04	12.73	23	63809	1831	32447863
Productive cough	22.82	12.73	20	63812	34096	32415598
Cerebrovascular accident	22.56	12.73	90	63742	86230	32363464
Tumour marker increased	22.54	12.73	14	63818	554	32449140
Mucosal toxicity	22.53	12.73	10	63822	195	32449499
Sarcoidosis	22.46	12.73	28	63804	2851	32446843
Mobility decreased	22.44	12.73	14	63818	28395	32421299
Type II hypersensitivity	22.43	12.73	6	63826	21	32449673
Abnormal behaviour	22.39	12.73	12	63820	26454	32423240
Aplasia	22.36	12.73	35	63797	4407	32445287
Portal venous gas	22.23	12.73	12	63820	363	32449331
Trichomegaly	21.80	12.73	6	63826	24	32449670
Varices oesophageal	21.50	12.73	31	63801	3630	32446064
Acne	21.48	12.73	56	63776	10186	32439508
Oral pain	21.38	12.73	55	63777	9923	32439771
Fluid overload	21.37	12.73	6	63826	19615	32430079
Cholecystitis chronic	21.20	12.73	16	63816	873	32448821
Haemorrhage intracranial	21.17	12.73	3	63829	15884	32433810
Rectal tenesmus	21.11	12.73	14	63818	621	32449073
Stoma site haemorrhage	21.10	12.73	17	63815	1021	32448673
Oesophageal haemorrhage	20.87	12.73	18	63814	1189	32448505
Fistula	20.72	12.73	38	63794	5441	32444253
Product administration error	20.71	12.73	3	63829	15622	32434072
Ischiorectal hernia	20.70	12.73	5	63827	10	32449684
Mouth ulceration	20.58	12.73	59	63773	11342	32438352
Pulmonary infarction	20.56	12.73	18	63814	1213	32448481
Haematopoietic stem cell mobilisation	20.54	12.73	9	63823	170	32449524
Hypertension	20.50	12.73	368	63464	131382	32318312
Contraindicated product administered	20.47	12.73	6	63826	19070	32430624
Anastomotic fistula	20.46	12.73	7	63825	65	32449629
Deep vein thrombosis	20.43	12.73	203	63629	63510	32386184
Agitation	20.33	12.73	52	63780	57184	32392510
Cranial nerve disorder	20.22	12.73	12	63820	437	32449257
Eosinophilia	20.13	12.73	12	63820	24946	32424748
Abdominal discomfort	20.12	12.73	46	63786	52578	32397116
Metastasis	20.08	12.73	30	63802	3627	32446067
Peritonitis	20.05	12.73	92	63740	22238	32427456
Hepatectomy	20.00	12.73	7	63825	70	32449624
Haemolytic anaemia	19.98	12.73	56	63776	10628	32439066
Dysphonia	19.91	12.73	87	63745	20597	32429097
Pulmonary artery thrombosis	19.91	12.73	14	63818	684	32449010
Eyelash changes	19.80	12.73	5	63827	13	32449681
Hypersplenism	19.76	12.73	11	63821	354	32449340
Organising pneumonia	19.74	12.73	38	63794	5643	32444051
Bronchitis	19.60	12.73	32	63800	41475	32408219
Road traffic accident	19.53	12.73	5	63827	17376	32432318
Thrombotic thrombocytopenic purpura	19.51	12.73	29	63803	3491	32446203
Flushing	19.48	12.73	116	63716	31011	32418683
Rectal abscess	19.37	12.73	16	63816	996	32448698
Sepsis	19.15	12.73	427	63405	158407	32291287
Lung neoplasm malignant	19.11	12.73	4	63828	15959	32433735
K-ras gene mutation	19.03	12.73	5	63827	16	32449678
Acute motor-sensory axonal neuropathy	18.97	12.73	8	63824	137	32449557
Dysaesthesia	18.90	12.73	23	63809	2285	32447409
Bacterial colitis	18.90	12.73	6	63826	43	32449651
ECG signs of myocardial ischaemia	18.88	12.73	9	63823	208	32449486
Performance status decreased	18.87	12.73	31	63801	4067	32445627
Diffuse alveolar damage	18.80	12.73	22	63810	2097	32447597
Gastrointestinal inflammation	18.76	12.73	27	63805	3157	32446537
Posterior reversible encephalopathy syndrome	18.70	12.73	51	63781	9525	32440169
Chronic kidney disease	18.70	12.73	31	63801	39944	32409750
Jaundice	18.70	12.73	123	63709	34035	32415659
Hyperkalaemia	18.68	12.73	72	63760	69678	32380016
Malignant ascites	18.67	12.73	11	63821	395	32449299
Pneumonitis	18.67	12.73	112	63720	30022	32419672
Hepatitis B surface antigen positive	18.66	12.73	8	63824	143	32449551
Arthritis	18.65	12.73	15	63817	26677	32423017
Tremor	18.65	12.73	89	63743	81188	32368506
Intentional product use issue	18.60	12.73	34	63798	42177	32407517
B-cell small lymphocytic lymphoma	18.46	12.73	8	63824	147	32449547
Pseudocirrhosis	18.37	12.73	5	63827	19	32449675
Visceral venous thrombosis	18.17	12.73	5	63827	20	32449674
Oesophagobronchial fistula	18.17	12.73	8	63824	153	32449541
Stoma site pain	18.15	12.73	15	63817	934	32448760
Embolism	18.14	12.73	43	63789	7371	32442323
Respiratory arrest	18.10	12.73	18	63814	28890	32420804
Angioedema	18.06	12.73	27	63805	36262	32413432
Allodynia	18.06	12.73	13	63819	659	32449035
Gastric perforation	17.88	12.73	22	63810	2211	32447483
Perforation bile duct	17.80	12.73	6	63826	53	32449641
Renal disorder	17.79	12.73	14	63818	25169	32424525
Emotional distress	17.74	12.73	5	63827	16301	32433393
Liver function test abnormal	17.69	12.73	22	63810	31925	32417769
Diabetes mellitus	17.67	12.73	39	63793	45134	32404560
Duodenal perforation	17.52	12.73	17	63815	1308	32448386
Soft tissue swelling	17.47	12.73	10	63822	340	32449354
Immune thrombocytopenia	17.35	12.73	46	63786	8451	32441243
Rectosigmoid cancer	17.31	12.73	8	63824	172	32449522
Organic brain syndrome	17.31	12.73	9	63823	252	32449442
Heart rate increased	17.29	12.73	35	63797	41793	32407901
Toxoplasmosis	17.26	12.73	17	63815	1332	32448362
Non-cirrhotic portal hypertension	17.18	12.73	9	63823	256	32449438
Guillain-Barre syndrome	17.08	12.73	35	63797	5439	32444255
Irritability	17.04	12.73	14	63818	24640	32425054
Neutrophil count decreased	17	12.73	154	63678	46985	32402709
Neurosarcoidosis	16.98	12.73	8	63824	180	32449514
Perineal disorder	16.97	12.73	6	63826	62	32449632
Catheter site extravasation	16.92	12.73	7	63825	114	32449580
Hepatic pain	16.88	12.73	17	63815	1368	32448326
Dyskinesia	16.82	12.73	13	63819	23590	32426104
Gastrointestinal anastomotic leak	16.80	12.73	10	63822	366	32449328
Electromyogram abnormal	16.80	12.73	6	63826	64	32449630
Proctitis	16.78	12.73	22	63810	2356	32447338
Stress cardiomyopathy	16.62	12.73	19	63813	1767	32447927
Change of bowel habit	16.58	12.73	15	63817	1056	32448638
Pelvic inflammatory disease	16.56	12.73	4	63828	8	32449686
Intrahepatic portal hepatic venous fistula	16.56	12.73	4	63828	8	32449686
Laryngospasm	16.52	12.73	17	63815	1404	32448290
Streptococcal bacteraemia	16.50	12.73	19	63813	1781	32447913
Drug hypersensitivity	16.47	12.73	81	63751	73319	32376375
Respiratory depression	16.47	12.73	3	63829	13208	32436486
Intestinal strangulation	16.37	12.73	5	63827	31	32449663
Nasopharyngitis	16.35	12.73	67	63765	63720	32385974
Retroperitoneal abscess	16.32	12.73	8	63824	197	32449497
Metastases to pelvis	16.27	12.73	9	63823	286	32449408
Vocal cord paralysis	16.14	12.73	14	63818	932	32448762
Radiation interaction	16.10	12.73	5	63827	33	32449661
Renal impairment	16.09	12.73	110	63722	91862	32357832
Haematoma	16.07	12.73	16	63816	25668	32424026
Tumour fistulisation	15.95	12.73	4	63828	10	32449684
Off label use	15.87	12.73	744	63088	305576	32144118
Septic shock	15.86	12.73	206	63626	68783	32380911
Product quality issue	15.86	12.73	9	63823	19224	32430470
Brief psychotic disorder with marked stressors	15.78	12.73	8	63824	212	32449482
Neck pain	15.68	12.73	13	63819	22774	32426920
Astringent therapy	15.68	12.73	4	63828	11	32449683
Candida infection	15.66	12.73	70	63762	16733	32432961
Colorectal cancer recurrent	15.61	12.73	5	63827	37	32449657
Paraneoplastic syndrome	15.60	12.73	11	63821	540	32449154
Odynophagia	15.50	12.73	32	63800	4999	32444695
Balance disorder	15.48	12.73	34	63798	39425	32410269
Heart rate decreased	15.42	12.73	16	63816	25184	32424510
Temperature difference of extremities	15.42	12.73	4	63828	12	32449682
Abscess	15.39	12.73	51	63781	10599	32439095
Lip swelling	15.39	12.73	4	63828	13761	32435933
Acinetobacter sepsis	15.38	12.73	5	63827	39	32449655
Bladder hypertrophy	15.33	12.73	11	63821	555	32449139
Periportal sinus dilatation	15.16	12.73	5	63827	41	32449653
Xerosis	15.14	12.73	11	63821	566	32449128
Neutropenic sepsis	15.07	12.73	57	63775	12642	32437052
Injection site erythema	15.05	12.73	5	63827	14663	32435031
Retinitis viral	15.01	12.73	6	63826	89	32449605
Pelvic venous thrombosis	15.00	12.73	11	63821	574	32449120
Portal shunt	14.95	12.73	5	63827	43	32449651
Swelling	14.94	12.73	33	63799	38189	32411505
Hypoacusis	14.92	12.73	6	63826	15635	32434059
Pneumonia aspiration	14.92	12.73	37	63795	41119	32408575
Limbic encephalitis	14.89	12.73	9	63823	339	32449355
Accidental overdose	14.63	12.73	10	63822	19329	32430365
Seizure	14.54	12.73	132	63700	103722	32345972
Paraesthesia mucosal	14.53	12.73	4	63828	16	32449678
Peritoneal adhesions	14.43	12.73	6	63826	99	32449595
Urticaria	14.43	12.73	64	63768	59550	32390144
Cerebral haemorrhage	14.42	12.73	29	63803	34718	32414976
Palmar erythema	14.36	12.73	8	63824	258	32449436
Gait inability	14.34	12.73	11	63821	20036	32429658
Rectal cancer recurrent	14.34	12.73	4	63828	17	32449677
Extrapyramidal disorder	14.20	12.73	3	63829	11892	32437802
Blood pressure decreased	14.15	12.73	52	63780	51028	32398666
Dyspnoea	14.03	12.73	575	63257	361470	32088224
Prostate cancer	14.02	12.73	20	63812	27386	32422308
Cardiac arrest	13.99	12.73	122	63710	96654	32353040
Full blood count decreased	13.97	12.73	8	63824	17002	32432692
Hepatic cancer recurrent	13.97	12.73	9	63823	380	32449314
Gout	13.75	12.73	10	63822	18718	32430976
Faeces discoloured	13.72	12.73	6	63826	14871	32434823
Gastrointestinal haemorrhage	13.71	12.73	107	63725	86775	32362919
Dry skin	13.70	12.73	90	63742	24888	32424806
Urinary tract obstruction	13.70	12.73	25	63807	3566	32446128
Psychotic disorder	13.66	12.73	15	63817	23005	32426689
VIth nerve disorder	13.65	12.73	4	63828	21	32449673
Injection site reaction	13.64	12.73	3	63829	11566	32438128
Anorectal infection	13.56	12.73	7	63825	193	32449501
Pulmonary oedema	13.55	12.73	46	63786	46221	32403473
Onychoclasis	13.48	12.73	17	63815	1751	32447943
Tracheal inflammation	13.47	12.73	5	63827	60	32449634
Herpes zoster	13.42	12.73	27	63805	32314	32417380
Malaise	13.41	12.73	256	63576	176882	32272812
Prostatic calcification	13.38	12.73	6	63826	120	32449574
Aphthous ulcer	13.35	12.73	28	63804	4423	32445271
Peritoneal disorder	13.24	12.73	9	63823	416	32449278
Blood glucose decreased	13.22	12.73	5	63827	13529	32436165
Visual impairment	13.18	12.73	28	63804	32860	32416834
Tumour perforation	13.15	12.73	8	63824	305	32449389
Hepatitis B DNA increased	13.10	12.73	10	63822	555	32449139
Ocular toxicity	13.08	12.73	7	63825	208	32449486
Crystal nephropathy	13.07	12.73	9	63823	425	32449269
Klebsiella infection	13.07	12.73	40	63792	7972	32441722
Pleural fistula	13.07	12.73	4	63828	25	32449669
Iatrogenic infection	13.04	12.73	5	63827	66	32449628
Bacteriuria	13.01	12.73	8	63824	311	32449383
Laboratory test abnormal	13.00	12.73	11	63821	19076	32430618
Nephrolithiasis	12.99	12.73	21	63811	27333	32422361
Metastatic neoplasm	12.99	12.73	22	63810	2959	32446735
Demyelinating polyneuropathy	12.91	12.73	14	63818	1228	32448466
Erectile dysfunction	12.83	12.73	12	63820	19827	32429867
Blood lactic acid increased	12.82	12.73	34	63798	6247	32443447
Gastrooesophageal reflux disease	12.77	12.73	31	63801	34707	32414987

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 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
CHEBI has role	CHEBI:75771	Mus musculus metabolite
CHEBI has role	CHEBI:76971	E.coli metabolites
FDA EPC	N0000178369	Folate Analog

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
4019798	VUID
N0000147887	NUI
D01211	KEGG_DRUG
1492-18-8	SECONDARY_CAS_RN
4018768	VANDF
4019798	VANDF
4031236	VANDF
C0023413	UMLSCUI
CHEBI:15640	CHEBI
CHEMBL1679	ChEMBL_ID
CHEMBL3707260	ChEMBL_ID
CHEMBL1232801	ChEMBL_ID
CHEMBL1201138	ChEMBL_ID
D002955	MESH_DESCRIPTOR_UI
DB00650	DRUGBANK_ID
4816	IUPHAR_LIGAND_ID
690	INN_ID
Q573I9DVLP	UNII
135403648	PUBCHEM_CID
225852	RXNORM
1728	MMSL
39896	MMSL
4964	MMSL
51342	MMSL
d00275	MMSL
001050	NDDF
001051	NDDF
009520	NDDF
126223008	SNOMEDCT_US
1528001	SNOMEDCT_US
396065004	SNOMEDCT_US
768550004	SNOMEDCT_US

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	15 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4497	TABLET	10 mg	ORAL	ANDA	15 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4498	TABLET	15 mg	ORAL	ANDA	15 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-4499	TABLET	25 mg	ORAL	ANDA	15 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0054-8496	TABLET	5 mg	ORAL	ANDA	15 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9368	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAMUSCULAR	ANDA	19 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9552	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAMUSCULAR	ANDA	19 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9553	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAMUSCULAR	ANDA	19 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9554	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAMUSCULAR	ANDA	19 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9555	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAMUSCULAR	ANDA	19 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0555-0484	TABLET	5 mg	ORAL	ANDA	17 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0555-0485	TABLET	25 mg	ORAL	ANDA	17 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5140	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAMUSCULAR	ANDA	18 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5145	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAMUSCULAR	ANDA	18 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5145	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAMUSCULAR	ANDA	18 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6703	TABLET	25 mg	ORAL	ANDA	15 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-813	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	ANDA	21 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-814	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	21 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-815	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	200 mg	INTRAVENOUS	ANDA	21 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-816	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	350 mg	INTRAVENOUS	ANDA	21 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	25021-828	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	ANDA	21 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	42806-133	TABLET	10 mg	ORAL	ANDA	16 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	42806-134	TABLET	15 mg	ORAL	ANDA	16 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	42806-358	TABLET	5 mg	ORAL	ANDA	16 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	42806-359	TABLET	25 mg	ORAL	ANDA	16 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	50742-181	TABLET	5 mg	ORAL	ANDA	17 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	50742-182	TABLET	10 mg	ORAL	ANDA	17 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	50742-183	TABLET	15 mg	ORAL	ANDA	17 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	50742-184	TABLET	25 mg	ORAL	ANDA	17 sections
Leucovorin Calcium	HUMAN PRESCRIPTION DRUG LABEL	1	51079-581	TABLET	5 mg	ORAL	ANDA	17 sections