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

Stem definitionDrug idCAS RN
1232 58-05-9

Description:

MoleculeDescription

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:

DoseUnitRoute
60 mg O
60 mg P
60 mg P

ADMET properties:

PropertyValueReference
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:

DateAgencyCompanyOrphan
June 20, 1952 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Thymidylate synthase Enzyme Ki 4.07 WOMBAT-PK
Dihydrofolate reductase Enzyme Ki 5.63 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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