pemetrexed 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antineoplastics; thymidylate synthetase inhibitors 2073 137281-23-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • LY231514
  • pemetrexed diacid monohydrate
  • pemetrexed sodium
  • pemetrexed sodium hydrate
  • pemetrexed
  • pemetrexed disodium
  • alimta
  • pemetrexed disodium heptahydrate
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT.
  • Molecular weight: 427.42
  • Formula: C20H21N5O6
  • CLOGP: -0.12
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 6
  • TPSA: 186.97
  • ALOGS: -3.97
  • ROTB: 9
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 100 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 80 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.38 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 0.15 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.19 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.85 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

DateAgencyCompanyOrphan
Sept. 20, 2004 EMA ELI LILLY NEDERLAND B.V.
Feb. 4, 2004 FDA LILLY
Jan. 4, 2007 PMDA Eli Lilly Japan K.K.

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
Malignant neoplasm progression 1603.19 19.89 767 30635 106103 90490942
Disease progression 758.79 19.89 540 30862 156075 90440970
Pancytopenia 655.55 19.89 446 30956 119817 90477228
Tubulointerstitial nephritis 498.12 19.89 220 31182 25123 90571922
Anaemia 422.22 19.89 563 30839 352239 90244806
Neutropenia 345.45 19.89 407 30995 224497 90372548
Therapy partial responder 334.74 19.89 160 31242 21883 90575162
Pneumonitis 327.31 19.89 199 31203 43971 90553074
Non-small cell lung cancer 299.62 19.89 95 31307 4286 90592759
Febrile neutropenia 287.96 19.89 313 31089 158036 90439009
Acute kidney injury 278.69 19.89 440 30962 319947 90277098
Thrombocytopenia 272.27 19.89 348 31054 208377 90388668
Myelosuppression 259.30 19.89 185 31217 53406 90543639
Renal tubular necrosis 256.11 19.89 117 31285 14438 90582607
Neoplasm progression 251.48 19.89 169 31233 44317 90552728
Drug resistance 243.20 19.89 144 31258 30305 90566740
Immune-mediated lung disease 221.17 19.89 62 31340 1818 90595227
Metastases to central nervous system 194.72 19.89 103 31299 17439 90579606
Mucosal inflammation 193.26 19.89 160 31242 57465 90539580
Hepatic cytolysis 173.62 19.89 117 31285 30799 90566246
Acquired gene mutation 172.68 19.89 47 31355 1232 90595813
Hypothyroidism 168.81 19.89 143 31259 52984 90544061
Bone marrow failure 148.41 19.89 108 31294 32113 90564932
Pulmonary embolism 147.08 19.89 203 31199 130617 90466428
Immune-mediated enterocolitis 139.61 19.89 55 31347 4702 90592343
Rash maculo-papular 137.94 19.89 114 31288 40819 90556226
Haematotoxicity 137.41 19.89 73 31329 12462 90584583
Skin toxicity 136.83 19.89 60 31342 6719 90590326
Joint swelling 136.23 19.89 10 31392 503290 90093755
Hyperthyroidism 134.29 19.89 82 31320 18228 90578817
Renal failure 129.18 19.89 191 31211 130816 90466229
Pain 127.36 19.89 96 31306 996245 89600800
Pleural effusion 126.19 19.89 174 31228 111817 90485228
Myocarditis 122.68 19.89 70 31332 13736 90583309
Arthralgia 120.27 19.89 60 31342 778462 89818583
Colitis 117.87 19.89 133 31269 69809 90527236
Paronychia 115.10 19.89 56 31346 7950 90589095
Abdominal discomfort 114.75 19.89 15 31387 477313 90119732
Febrile bone marrow aplasia 113.25 19.89 59 31343 9679 90587366
Nephropathy toxic 111.85 19.89 64 31338 12624 90584421
Interstitial lung disease 105.12 19.89 131 31271 76274 90520771
Maternal exposure during pregnancy 103.90 19.89 5 31397 360058 90236987
Subacute cutaneous lupus erythematosus 103.67 19.89 41 31361 3541 90593504
Glossodynia 97.84 19.89 3 31399 321776 90275269
Neutrophil count decreased 97.38 19.89 122 31280 71410 90525635
Contraindicated product administered 97.28 19.89 3 31399 320136 90276909
Immune-mediated hepatitis 96.91 19.89 37 31365 2907 90594138
Sinusitis 95.16 19.89 6 31396 343082 90253963
Nasopharyngitis 92.70 19.89 15 31387 407089 90189956
Hypokalaemia 92.18 19.89 164 31238 130952 90466093
Blood creatinine increased 91.66 19.89 142 31260 101244 90495801
Metastases to adrenals 91.56 19.89 27 31375 951 90596094
EGFR gene mutation 87.37 19.89 21 31381 329 90596716
Arthropathy 86.81 19.89 12 31390 366230 90230815
Platelet count decreased 84.56 19.89 162 31240 136807 90460238
Death 84.34 19.89 347 31055 456204 90140841
Drug hypersensitivity 84.00 19.89 28 31374 463581 90133464
Lung adenocarcinoma 83.24 19.89 40 31362 5525 90591520
Wound 81.96 19.89 6 31396 302974 90294071
Dermatitis acneiform 81.13 19.89 41 31361 6313 90590732
Peripheral swelling 80.17 19.89 22 31380 413084 90183961
Swelling 80.06 19.89 23 31379 419035 90178010
Systemic lupus erythematosus 78.74 19.89 15 31387 361881 90235164
Weight increased 77.91 19.89 24 31378 417903 90179142
Pericardial effusion 77.85 19.89 79 31323 36754 90560291
Fall 75.99 19.89 36 31366 481774 90115271
Immune-mediated hepatic disorder 75.49 19.89 27 31375 1765 90595280
Metastases to meninges 75.19 19.89 33 31369 3702 90593343
Therapeutic product effect decreased 73.66 19.89 6 31396 277565 90319480
Hepatotoxicity 73.54 19.89 85 31317 45757 90551288
Renal impairment 72.97 19.89 131 31271 105290 90491755
Rheumatoid arthritis 72.85 19.89 18 31384 362596 90234449
Hypomagnesaemia 72.80 19.89 75 31327 35513 90561532
Malignant transformation 71.48 19.89 20 31382 582 90596463
Immune-mediated dermatitis 71.22 19.89 22 31380 909 90596136
Hypertransaminasaemia 70.49 19.89 52 31350 15773 90581272
Dehydration 70.48 19.89 186 31216 194261 90402784
Leukopenia 68.25 19.89 124 31278 100586 90496459
Asthma 67.84 19.89 4 31398 242156 90354889
Haemoptysis 67.76 19.89 70 31332 33250 90563795
Nephritis 66.82 19.89 29 31373 3166 90593879
Posterior reversible encephalopathy syndrome 66.59 19.89 58 31344 22281 90574764
Lymphangiosis carcinomatosa 65.96 19.89 24 31378 1648 90595397
Osteonecrosis of jaw 65.24 19.89 74 31328 39029 90558016
Discomfort 64.96 19.89 9 31393 274326 90322719
Insomnia 64.23 19.89 18 31384 333456 90263589
Immune-mediated myocarditis 63.60 19.89 22 31380 1303 90595742
Hypophysitis 63.12 19.89 26 31376 2494 90594551
Oesophagitis 62.22 19.89 50 31352 17199 90579846
Product dose omission issue 61.53 19.89 13 31389 291674 90305371
Toxic epidermal necrolysis 60.21 19.89 65 31337 32463 90564582
Tumour pseudoprogression 59.25 19.89 18 31384 703 90596342
Dermatitis bullous 57.80 19.89 39 31363 10277 90586768
Contusion 57.72 19.89 9 31393 251207 90345838
Hepatocellular injury 57.38 19.89 60 31342 28898 90568147
Hepatitis 56.94 19.89 94 31308 70645 90526400
Metastases to lung 56.93 19.89 46 31356 15945 90581100
Exposure during pregnancy 56.02 19.89 8 31394 238402 90358643
Myasthenic syndrome 55.71 19.89 15 31387 377 90596668
Immune-mediated arthritis 55.36 19.89 14 31388 273 90596772
Hepatic function abnormal 55.24 19.89 74 31328 46214 90550831
Pericarditis 55.05 19.89 13 31389 270138 90326907
White blood cell count decreased 53.72 19.89 153 31249 166956 90430089
Ischaemic stroke 53.26 19.89 51 31351 22115 90574930
Dermo-hypodermitis 53.11 19.89 17 31385 790 90596255
Hypocalcaemia 52.51 19.89 69 31333 42299 90554746
Metastases to liver 52.33 19.89 57 31345 28750 90568295
Type 2 diabetes mellitus 52.27 19.89 5 31397 203239 90393806
Vomiting 51.90 19.89 457 30945 787836 89809209
Nausea 51.67 19.89 599 30803 1109717 89487328
Wheezing 51.48 19.89 10 31392 238070 90358975
Headache 50.88 19.89 143 31259 862603 89734442
Radiotherapy 50.65 19.89 17 31385 918 90596127
Transaminases increased 49.90 19.89 63 31339 37129 90559916
Lichenoid keratosis 49.75 19.89 22 31380 2512 90594533
Muscle spasms 49.61 19.89 13 31389 251870 90345175
Malignant pleural effusion 49.54 19.89 23 31379 2941 90594104
Non-small cell lung cancer recurrent 49.36 19.89 11 31391 121 90596924
Immune-mediated hypothyroidism 49.20 19.89 19 31383 1539 90595506
Ill-defined disorder 49.03 19.89 4 31398 184887 90412158
Metastases to bone 49.03 19.89 52 31350 25453 90571592
Non-small cell lung cancer metastatic 48.82 19.89 16 31386 802 90596243
Hypoaesthesia 48.70 19.89 24 31378 314186 90282859
Drug intolerance 48.67 19.89 50 31352 447541 90149504
Blister 48.65 19.89 14 31388 254984 90342061
Peripheral ischaemia 48.38 19.89 28 31374 5639 90591406
Migraine 48.13 19.89 5 31397 190387 90406658
Cholestasis 47.93 19.89 61 31341 36238 90560807
Renal tubular disorder 47.81 19.89 23 31379 3184 90593861
Alopecia 47.66 19.89 61 31341 495010 90102035
Hyperphosphaturia 47.12 19.89 9 31393 42 90597003
Immune-mediated pancreatitis 46.90 19.89 13 31389 365 90596680
Gene mutation 46.73 19.89 20 31382 2110 90594935
Gastrointestinal toxicity 46.48 19.89 33 31369 9434 90587611
Impaired healing 46.29 19.89 12 31390 234187 90362858
Pain in extremity 46.02 19.89 53 31349 450476 90146569
Radiation pneumonitis 45.96 19.89 19 31383 1839 90595206
Gamma-glutamyltransferase increased 45.79 19.89 61 31341 37891 90559154
Sleep disorder 45.70 19.89 7 31395 198023 90399022
Microvascular coronary artery disease 45.66 19.89 12 31390 274 90596771
Toxic skin eruption 45.10 19.89 40 31362 15734 90581311
Hepatic enzyme increased 44.31 19.89 36 31366 360700 90236345
Immune-mediated nephritis 44.05 19.89 13 31389 459 90596586
Mobility decreased 43.89 19.89 16 31386 250718 90346327
Scleroedema 43.34 19.89 10 31392 130 90596915
Memory impairment 43.24 19.89 8 31394 197236 90399809
Melanoderma 43.14 19.89 11 31391 222 90596823
Urticaria 42.57 19.89 28 31374 312706 90284339
Cholangitis 42.27 19.89 28 31374 7154 90589891
Depression 42.17 19.89 26 31376 300575 90296470
Secondary adrenocortical insufficiency 41.92 19.89 19 31383 2299 90594746
Bicytopenia 41.43 19.89 22 31380 3749 90593296
Autoimmune colitis 41.41 19.89 14 31388 773 90596272
Decreased appetite 41.34 19.89 247 31155 376293 90220752
Metastasis 41.23 19.89 26 31376 6111 90590934
Lung cancer metastatic 40.76 19.89 20 31382 2891 90594154
Hypersensitivity 40.75 19.89 59 31343 454618 90142427
Diarrhoea 40.66 19.89 500 30902 938690 89658355
Neonatal respiratory depression 39.99 19.89 10 31392 186 90596859
Lower respiratory tract infection 39.05 19.89 19 31383 250640 90346405
Adenocarcinoma 38.99 19.89 20 31382 3176 90593869
Performance status decreased 38.82 19.89 22 31380 4258 90592787
Proteinuria 38.72 19.89 44 31358 23247 90573798
Anaphylactic shock 38.42 19.89 51 31351 31566 90565479
Sepsis 38.22 19.89 143 31259 179671 90417374
Hyperamylasaemia 37.99 19.89 12 31390 534 90596511
Respiratory failure 37.63 19.89 108 31294 118310 90478735
Aspartate aminotransferase increased 36.78 19.89 98 31304 102839 90494206
Asthenia 35.84 19.89 311 31091 533440 90063605
Folliculitis 35.83 19.89 13 31389 204340 90392705
Blood phosphorus abnormal 35.66 19.89 9 31393 174 90596871
Hepatitis cholestatic 35.61 19.89 27 31375 8534 90588511
Tumour associated fever 35.53 19.89 11 31391 458 90596587
Extremity necrosis 35.26 19.89 16 31386 1941 90595104
Autoimmune hepatitis 35.21 19.89 29 31373 10322 90586723
Systemic scleroderma 35.13 19.89 15 31387 1574 90595471
Enterocolitis 34.87 19.89 29 31373 10461 90586584
Nephrogenic diabetes insipidus 34.86 19.89 13 31389 957 90596088
Stasis dermatitis 34.86 19.89 13 31389 957 90596088
Erysipeloid 34.84 19.89 5 31397 0 90597045
Agranulocytosis 34.40 19.89 51 31351 34951 90562094
Gait inability 34.19 19.89 5 31397 146451 90450594
Alanine aminotransferase increased 33.86 19.89 104 31298 118234 90478811
Cardiotoxicity 32.80 19.89 29 31373 11360 90585685
Pseudocellulitis 32.61 19.89 8 31394 137 90596908
Scleroderma-like reaction 32.51 19.89 8 31394 139 90596906
Jaw operation 32.50 19.89 12 31390 859 90596186
Pulmonary toxicity 32.49 19.89 29 31373 11502 90585543
Dry mouth 31.77 19.89 12 31390 184047 90412998
Periorbital oedema 31.77 19.89 23 31379 6776 90590269
Papillary cystadenoma lymphomatosum 31.68 19.89 8 31394 155 90596890
Hypoalbuminaemia 31.60 19.89 33 31369 15864 90581181
Epistaxis 31.38 19.89 82 31320 85043 90512002
Aortic thrombosis 31.05 19.89 13 31389 1299 90595746
General physical health deterioration 31.03 19.89 220 31182 354895 90242150
Hepatitis toxic 30.73 19.89 18 31384 3707 90593338
Superinfection bacterial 30.63 19.89 12 31390 1010 90596035
Treatment failure 29.68 19.89 37 31365 303891 90293154
Embolism arterial 29.56 19.89 12 31390 1109 90595936
Carcinoembryonic antigen increased 29.52 19.89 15 31387 2335 90594710
Dizziness 29.51 19.89 105 31297 589179 90007866
Polyarthritis 29.38 19.89 34 31368 18316 90578729
Immune-mediated renal disorder 29.09 19.89 8 31394 218 90596827
Nephrosclerosis 29.07 19.89 12 31390 1157 90595888
Embolism 29.03 19.89 25 31377 9456 90587589
Gait disturbance 28.39 19.89 29 31373 260467 90336578
Mixed deafness 27.91 19.89 5 31397 15 90597030
Influenza 27.77 19.89 7 31395 139257 90457788
Nephropathy 27.57 19.89 24 31378 9211 90587834
Intentional product use issue 27.42 19.89 21 31381 216871 90380174
Cytopenia 27.38 19.89 32 31370 17417 90579628
Tracheal fistula 27.26 19.89 6 31396 62 90596983
Feeling abnormal 27.08 19.89 12 31390 167223 90429822
Non-small cell lung cancer stage IV 26.88 19.89 7 31395 154 90596891
Autoimmune dermatitis 26.84 19.89 7 31395 155 90596890
Secondary hypertension 26.77 19.89 8 31394 295 90596750
Night sweats 26.60 19.89 6 31396 128760 90468285
Tumour hyperprogression 26.46 19.89 7 31395 164 90596881
Unmasking of previously unidentified disease 26.38 19.89 12 31390 1464 90595581
Wound infection 26.36 19.89 3 31399 106399 90490646
Bronchitis 26.34 19.89 10 31392 152917 90444128
Eastern Cooperative Oncology Group performance status worsened 26.19 19.89 13 31389 1926 90595119
Overdose 26.04 19.89 11 31391 157698 90439347
Acute interstitial pneumonitis 25.91 19.89 10 31392 809 90596236
Lung adenocarcinoma recurrent 25.59 19.89 6 31396 84 90596961
Sarcomatoid carcinoma 25.42 19.89 5 31397 28 90597017
Off label use 24.95 19.89 527 30875 1101725 89495320
Psoriasis 24.89 19.89 10 31392 147744 90449301
Purpura 24.70 19.89 28 31374 14750 90582295
Venous thrombosis 24.22 19.89 18 31384 5519 90591526
Autoimmune nephritis 24.16 19.89 8 31394 414 90596631
Anxiety 24.16 19.89 44 31358 309728 90287317
Autoimmune lung disease 24.03 19.89 6 31396 111 90596934
Peptic ulcer perforation 23.52 19.89 8 31394 450 90596595
Drug eruption 23.21 19.89 43 31359 35364 90561681
Idiopathic interstitial pneumonia 23.17 19.89 7 31395 268 90596777
Thrombophlebitis migrans 23 19.89 7 31395 275 90596770
Autoimmune hypothyroidism 22.90 19.89 7 31395 279 90596766
BRAF V600E mutation positive 22.87 19.89 5 31397 50 90596995
Bronchogram abnormal 22.59 19.89 4 31398 11 90597034
Febrile infection 22.53 19.89 12 31390 2057 90594988
Burkholderia pseudomallei infection 22.44 19.89 5 31397 55 90596990
Anaplastic lymphoma kinase gene mutation 22.33 19.89 4 31398 12 90597033
Haemophagocytic lymphohistiocytosis 22.04 19.89 27 31375 15432 90581613
Systemic infection 21.96 19.89 16 31386 4759 90592286
Immune-mediated adverse reaction 21.94 19.89 9 31393 854 90596191
Lung neoplasm malignant 21.92 19.89 34 31368 24239 90572806
Pulmonary radiation injury 21.86 19.89 4 31398 14 90597031
Loss of personal independence in daily activities 21.67 19.89 10 31392 136095 90460950
Vascular purpura 21.56 19.89 11 31391 1727 90595318
Dose calculation error 21.49 19.89 7 31395 344 90596701
Renal arteriosclerosis 21.24 19.89 6 31396 181 90596864
Gastrooesophageal reflux disease 21.16 19.89 16 31386 166321 90430724
Small cell lung cancer 21.06 19.89 11 31391 1813 90595232
Thyroiditis 20.97 19.89 14 31388 3623 90593422
Large intestine perforation 20.82 19.89 21 31381 9691 90587354
Amnesia 20.60 19.89 6 31396 108499 90488546
Dysaesthesia 20.60 19.89 16 31386 5239 90591806
Neuropathy peripheral 20.56 19.89 98 31304 136872 90460173
Adrenal insufficiency 20.45 19.89 37 31365 29884 90567161
Blood pressure increased 20.32 19.89 23 31379 197194 90399851
Erysipelas 20.19 19.89 20 31382 9032 90588013
Encephalitis 20.16 19.89 22 31380 11112 90585933
Arthritis 20.15 19.89 17 31385 167298 90429747
Blood thyroid stimulating hormone increased 20.00 19.89 20 31382 9135 90587910
Autoimmune pericarditis 20.00 19.89 5 31397 93 90596952

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
Malignant neoplasm progression 1371.66 16.73 1044 44749 107356 42468186
Pancytopenia 905.32 16.73 852 44941 116891 42458651
Interstitial lung disease 507.01 16.73 517 45276 77945 42497597
Thrombocytopenia 378.69 16.73 708 45085 189571 42385971
Anaemia 375.05 16.73 886 44907 279392 42296150
Neutropenia 373.41 16.73 723 45070 198708 42376834
Disease progression 360.28 16.73 592 45201 143064 42432478
Pneumonitis 338.98 16.73 312 45481 41406 42534136
Myelosuppression 333.42 16.73 305 45488 40156 42535386
Febrile bone marrow aplasia 264.44 16.73 154 45639 10027 42565515
Pseudocellulitis 257.44 16.73 60 45733 223 42575319
Immune-mediated lung disease 229.39 16.73 99 45694 3374 42572168
Therapy partial responder 219.93 16.73 178 45615 19843 42555699
Febrile neutropenia 196.44 16.73 538 45255 185165 42390377
General physical health deterioration 193.77 16.73 471 45322 150775 42424767
Tubulointerstitial nephritis 192.77 16.73 202 45591 31346 42544196
Immune-mediated enterocolitis 183.10 16.73 99 45694 5578 42569964
Mucosal inflammation 181.78 16.73 244 45549 49130 42526412
Immune-mediated hepatic disorder 170.42 16.73 73 45720 2441 42573101
Colitis 160.62 16.73 223 45570 46349 42529193
Bone marrow failure 147.72 16.73 180 45613 32913 42542629
Neoplasm progression 146.43 16.73 168 45625 28832 42546710
Metastases to central nervous system 139.68 16.73 104 45689 10251 42565291
Non-small cell lung cancer 136.50 16.73 78 45715 4896 42570646
Hepatic cytolysis 127.98 16.73 151 45642 26693 42548849
Leukopenia 127.29 16.73 261 45532 74485 42501057
Decreased appetite 124.17 16.73 472 45321 192665 42382877
Product dose omission issue 122.60 16.73 12 45781 154353 42421189
Skin toxicity 121.57 16.73 80 45713 6469 42569073
Haematotoxicity 115.01 16.73 95 45698 10890 42564652
Nephritis 108.23 16.73 61 45732 3728 42571814
Pulmonary toxicity 108.04 16.73 83 45710 8572 42566970
Immune-mediated hepatitis 105.76 16.73 60 45733 3714 42571828
Neutrophil count decreased 102.75 16.73 217 45576 63198 42512344
Pleural effusion 101.97 16.73 281 45512 96885 42478657
Acute kidney injury 97.98 16.73 702 45091 366635 42208907
Lichenoid keratosis 97.94 16.73 58 45735 3892 42571650
Immune-mediated dermatitis 96.78 16.73 40 45753 1221 42574321
Platelet count decreased 93.38 16.73 344 45449 138237 42437305
Immune-mediated hypothyroidism 93.02 16.73 39 45754 1235 42574307
Enteritis 87.95 16.73 81 45712 10735 42564807
Completed suicide 86.73 16.73 4 45789 96461 42479081
Fall 86.43 16.73 75 45718 234445 42341097
Hyperthyroidism 82.55 16.73 89 45704 14252 42561290
Hypothyroidism 71.88 16.73 126 45667 31958 42543584
Drug interaction 71.77 16.73 110 45683 266889 42308653
Immune-mediated myocarditis 71.00 16.73 38 45755 2096 42573446
Hypertransaminasaemia 70.97 16.73 67 45726 9160 42566382
Aplasia 70.64 16.73 51 45742 4792 42570750
Headache 68.86 16.73 94 45699 239275 42336267
EGFR gene mutation 67.78 16.73 20 45773 214 42575328
Nephropathy toxic 67.78 16.73 87 45706 16751 42558791
Pain in extremity 67.48 16.73 39 45754 150565 42424977
Septic shock 65.45 16.73 232 45561 91440 42484102
Hypercreatininaemia 65.20 16.73 24 45769 533 42575009
Renal tubular necrosis 64.90 16.73 89 45704 18265 42557277
Tumour pseudoprogression 63.06 16.73 28 45765 1022 42574520
Erysipelas 62.89 16.73 53 45740 6243 42569299
Muscle spasms 62.56 16.73 9 45784 86035 42489507
Overdose 62.11 16.73 18 45775 105246 42470296
Immune-mediated renal disorder 61.41 16.73 22 45771 451 42575091
Acquired gene mutation 60.76 16.73 31 45762 1549 42573993
Neutropenic sepsis 60.46 16.73 80 45713 15866 42559676
Extremity necrosis 59.99 16.73 35 45758 2284 42573258
Radiation pneumonitis 59.78 16.73 38 45755 2895 42572647
Bradycardia 59.74 16.73 10 45783 85474 42490068
Immune-mediated adrenal insuficiency 58.30 16.73 24 45769 725 42574817
Diarrhoea 56.86 16.73 749 45044 460100 42115442
Respiratory failure 55.96 16.73 279 45514 127853 42447689
Tremor 54.63 16.73 18 45775 96911 42478631
Myocarditis 54.08 16.73 83 45710 18855 42556687
Hypopituitarism 54.01 16.73 35 45758 2756 42572786
Adrenocorticotropic hormone deficiency 53.03 16.73 27 45766 1343 42574199
Renal impairment 52.44 16.73 246 45547 109982 42465560
Immune-mediated adverse reaction 51.91 16.73 24 45769 964 42574578
Metastases to meninges 51.79 16.73 30 45763 1931 42573611
Intentional product misuse 51.31 16.73 4 45789 61896 42513646
Haemophagocytic lymphohistiocytosis 50.83 16.73 79 45714 18143 42557399
Eastern Cooperative Oncology Group performance status worsened 50.76 16.73 26 45767 1310 42574232
Injection site pain 50.05 16.73 3 45790 57795 42517747
Neutropenic colitis 49.61 16.73 40 45753 4430 42571112
Hepatocellular injury 49.20 16.73 90 45703 23588 42551954
Blood pressure increased 49.16 16.73 24 45769 101904 42473638
Rash 47.93 16.73 481 45312 276473 42299069
Lung adenocarcinoma 47.37 16.73 42 45751 5297 42570245
Anxiety 47.26 16.73 35 45758 118525 42457017
Pulmonary embolism 47.06 16.73 253 45540 119359 42456183
White blood cell count decreased 45.82 16.73 237 45556 110159 42465383
Pneumothorax 45.81 16.73 87 45706 23456 42552086
Stomatitis 45.44 16.73 138 45655 50191 42525351
Nasopharyngitis 44.93 16.73 17 45776 83979 42491563
Rash maculo-papular 44.91 16.73 114 45679 37389 42538153
Nausea 44.40 16.73 634 45159 396165 42179377
Depression 44.23 16.73 33 45760 111330 42464212
Asthma 44.18 16.73 7 45786 62307 42513235
Hepatitis 43.69 16.73 93 45700 27207 42548335
Performance status decreased 43.62 16.73 38 45755 4682 42570860
Drug resistance 43.00 16.73 106 45687 34142 42541400
Weight increased 42.88 16.73 32 45761 107951 42467591
Hepatotoxicity 41.75 16.73 87 45706 25080 42550462
Feeling abnormal 41.04 16.73 12 45781 69774 42505768
Peripheral swelling 40.95 16.73 23 45770 90247 42485295
Small intestinal perforation 40.69 16.73 30 45763 2911 42572631
Paraneoplastic syndrome 40.55 16.73 19 45774 787 42574755
Musculoskeletal stiffness 39.82 16.73 7 45786 57758 42517784
Oesophagitis 39.62 16.73 64 45729 15183 42560359
Haemoptysis 39.28 16.73 124 45669 46043 42529499
Loss of personal independence in daily activities 39.18 16.73 4 45789 49812 42525730
Metastases to liver 39.02 16.73 66 45727 16260 42559282
Abdominal discomfort 38.98 16.73 16 45777 75239 42500303
Insomnia 38.64 16.73 42 45751 118211 42457331
Hiccups 38.55 16.73 56 45737 12115 42563427
Pericardial effusion 38.24 16.73 92 45701 29183 42546359
Rhabdomyolysis 38.18 16.73 18 45775 78001 42497541
Adrenal insufficiency 38.14 16.73 71 45722 18853 42556689
Immune-mediated cholangitis 37.97 16.73 16 45777 513 42575029
Hypophysitis 37.85 16.73 29 45764 2982 42572560
Vomiting 37.75 16.73 476 45317 289247 42286295
Hallucination 37.46 16.73 8 45785 57499 42518043
Subacute cutaneous lupus erythematosus 37.28 16.73 22 45771 1466 42574076
Myasthenic syndrome 37.17 16.73 18 45775 803 42574739
Arthralgia 37.01 16.73 106 45687 205132 42370410
Bicytopenia 36.41 16.73 29 45764 3155 42572387
Agitation 36.13 16.73 12 45781 64302 42511240
Heteroplasia 36.02 16.73 7 45786 7 42575535
Metastases to bone 35.57 16.73 60 45733 14749 42560793
Large intestine perforation 34.86 16.73 47 45746 9489 42566053
Renal failure 34.31 16.73 268 45525 143458 42432084
Dizziness 34.01 16.73 145 45648 249109 42326433
Bronchostenosis 33.94 16.73 14 45779 425 42575117
Hypersensitivity pneumonitis 33.64 16.73 23 45770 1981 42573561
Superior vena cava syndrome 33.35 16.73 16 45777 699 42574843
Pneumonia 33.28 16.73 637 45156 421512 42154030
Cardiac failure congestive 33.17 16.73 26 45767 85576 42489966
Thrombophlebitis migrans 32.74 16.73 13 45780 357 42575185
Memory impairment 32.69 16.73 7 45786 50215 42525327
Somnolence 32.50 16.73 64 45729 141041 42434501
Immune-mediated oesophagitis 31.92 16.73 8 45785 43 42575499
Malignant pleural effusion 31.78 16.73 22 45771 1933 42573609
Endocrine toxicity 31.70 16.73 7 45786 19 42575523
Intentional product use issue 31.58 16.73 19 45774 71814 42503728
Asthenia 31.46 16.73 449 45344 280344 42295198
Visceral leishmaniasis 31.40 16.73 18 45775 1136 42574406
Non-small cell lung cancer metastatic 30.85 16.73 16 45777 827 42574715
Gait disturbance 30.71 16.73 36 45757 97964 42477578
Toxic epidermal necrolysis 30.67 16.73 80 45713 26670 42548872
Electrocardiogram QT prolonged 30.56 16.73 7 45786 47938 42527604
Toxicity to various agents 30.21 16.73 135 45658 229001 42346541
Wrong technique in product usage process 29.75 16.73 5 45788 42630 42532912
Prostate cancer 29.51 16.73 6 45787 44637 42530905
Pain 29.51 16.73 149 45644 244699 42330843
Pyrexia 29.49 16.73 590 45203 393452 42182090
Secondary adrenocortical insufficiency 28.12 16.73 21 45772 2078 42573464
Hyperhidrosis 27.56 16.73 34 45759 90478 42485064
Lung cancer metastatic 27.51 16.73 24 45769 2962 42572580
Renal tubular disorder 27.43 16.73 30 45763 4879 42570663
Mobility decreased 27.34 16.73 3 45790 35303 42540239
Radiotherapy 27.24 16.73 15 45778 876 42574666
Hypertension 26.84 16.73 91 45702 167113 42408429
Pericarditis 26.54 16.73 50 45743 13394 42562148
Gene mutation 26.53 16.73 19 45774 1762 42573780
Pancreatic toxicity 26.36 16.73 7 45786 49 42575493
Immune thrombocytopenia 26.35 16.73 45 45748 11171 42564371
Unevaluable event 26.33 16.73 3 45790 34285 42541257
Ototoxicity 26.21 16.73 21 45772 2304 42573238
Cardiac disorder 26.00 16.73 10 45783 48922 42526620
Dehydration 25.80 16.73 249 45544 141518 42434024
Immune-mediated encephalitis 25.77 16.73 13 45780 634 42574908
Purpura 25.75 16.73 46 45747 11833 42563709
Drug hypersensitivity 25.64 16.73 42 45751 99347 42476195
Post procedural oedema 25.59 16.73 6 45787 23 42575519
Tumour necrosis 25.56 16.73 18 45775 1626 42573916
Sleep disorder 25.27 16.73 10 45783 48085 42527457
Aggression 25.23 16.73 8 45785 44155 42531387
Drug reaction with eosinophilia and systemic symptoms 25.17 16.73 7 45786 42068 42533474
Peritonitis 24.81 16.73 59 45734 18574 42556968
Incorrect dose administered 24.74 16.73 13 45780 52961 42522581
Hypoglycaemia 24.71 16.73 17 45776 59837 42515705
Flagellate dermatitis 24.71 16.73 8 45785 119 42575423
Hepatic function abnormal 24.43 16.73 115 45678 51452 42524090
Pericarditis malignant 24.43 16.73 7 45786 67 42575475
Carcinoembryonic antigen increased 24.42 16.73 14 45779 884 42574658
Scleroderma-like reaction 24.33 16.73 7 45786 68 42575474
Metastases to adrenals 24.27 16.73 15 45778 1087 42574455
Lethargy 24.23 16.73 10 45783 46880 42528662
Autoimmune hepatitis 24.03 16.73 30 45763 5615 42569927
Dacryostenosis acquired 23.99 16.73 10 45783 312 42575230
Heart rate decreased 23.96 16.73 5 45788 36527 42539015
Necrotising myositis 23.79 16.73 15 45778 1126 42574416
Swelling 23.46 16.73 15 45778 54870 42520672
Radiotherapy to bone 23.38 16.73 5 45788 11 42575531
Metastases to lung 23.19 16.73 43 45750 11381 42564161
Metastases to pleura 23.16 16.73 12 45781 619 42574923
Radiotherapy to lung 23.08 16.73 5 45788 12 42575530
Adrenal disorder 23.04 16.73 15 45778 1190 42574352
Seizure 22.65 16.73 61 45732 120500 42455042
Visual impairment 22.59 16.73 9 45784 43104 42532438
Lymphangiosis carcinomatosa 22.55 16.73 14 45779 1023 42574519
Vision blurred 22.51 16.73 15 45778 53684 42521858
Genital tract inflammation 22.23 16.73 6 45787 45 42575497
Acute generalised exanthematous pustulosis 22.22 16.73 36 45757 8559 42566983
Blood creatine phosphokinase abnormal 22.14 16.73 10 45783 380 42575162
Disturbance in attention 21.99 16.73 3 45790 29863 42545679
Drug ineffective 21.74 16.73 514 45279 629683 41945859
Oral fungal infection 21.71 16.73 17 45776 1804 42573738
Tracheo-oesophageal fistula 21.64 16.73 11 45782 545 42574997
Immune-mediated cytopenia 21.59 16.73 8 45785 181 42575361
Type 1 diabetes mellitus 21.53 16.73 28 45765 5459 42570083
Sinusitis 21.51 16.73 12 45781 47280 42528262
Lactic acidosis 21.30 16.73 11 45782 45250 42530292
Metastases to peritoneum 21.20 16.73 19 45774 2430 42573112
Lacrimation disorder 21.11 16.73 4 45789 3 42575539
Coma 21.08 16.73 16 45777 53538 42522004
Thrombotic thrombocytopenic purpura 20.83 16.73 23 45770 3781 42571761
Dermatitis acneiform 20.81 16.73 33 45760 7706 42567836
Confusional state 20.74 16.73 101 45692 167496 42408046
Oral papule 20.58 16.73 4 45789 4 42575538
Hospitalisation 20.52 16.73 30 45763 74300 42501242
Cataract 20.46 16.73 4 45789 30600 42544942
Lung adenocarcinoma recurrent 20.11 16.73 4 45789 5 42575537
COVID-19 20.06 16.73 61 45732 115887 42459655
Contusion 20.06 16.73 10 45783 41975 42533567
Troponin abnormal 19.94 16.73 6 45787 69 42575473
Rheumatoid nodule 19.76 16.73 20 45773 2975 42572567
Gastrooesophageal reflux disease 19.66 16.73 12 45781 45011 42530531
Influenza like illness 19.60 16.73 5 45788 31835 42543707
Nasal congestion 19.43 16.73 4 45789 29497 42546045
Gastrointestinal perforation 19.35 16.73 24 45769 4462 42571080
Joint swelling 19.22 16.73 27 45766 67995 42507547
Psychotic disorder 19.15 16.73 4 45789 29204 42546338
Autoimmune lung disease 19.00 16.73 6 45787 82 42575460
Nephrolithiasis 18.79 16.73 8 45785 36822 42538720
Palmar erythema 18.73 16.73 10 45783 549 42574993
Immune-mediated cystitis 18.67 16.73 6 45787 87 42575455
Lymphadenopathy mediastinal 18.60 16.73 20 45773 3191 42572351
Product prescribing error 18.36 16.73 3 45790 26109 42549433
Gastrointestinal toxicity 18.32 16.73 22 45771 3957 42571585
Blood glucose increased 18.22 16.73 32 45761 73667 42501875
Gout 18.07 16.73 4 45789 28051 42547491
Diabetic ketoacidotic hyperglycaemic coma 18.02 16.73 7 45786 181 42575361
Opsoclonus myoclonus 18.01 16.73 6 45787 98 42575444
Magnetic resonance imaging abnormal 17.97 16.73 15 45778 1743 42573799
Bacterial prostatitis 17.96 16.73 6 45787 99 42575443
Superior mesenteric artery syndrome 17.90 16.73 6 45787 100 42575442
Lung disorder 17.90 16.73 100 45693 47823 42527719
Loss of consciousness 17.89 16.73 46 45747 92308 42483234
Spinal cord abscess 17.88 16.73 9 45784 437 42575105
Hypoaesthesia 17.69 16.73 31 45762 71432 42504110
Dyskinesia 17.66 16.73 3 45790 25387 42550155
No adverse event 17.60 16.73 10 45783 39011 42536531
Immune-mediated myositis 17.51 16.73 21 45772 3772 42571770
Occipital neuralgia 17.43 16.73 5 45788 48 42575494
Cutaneous lupus erythematosus 17.34 16.73 11 45782 835 42574707
Lymphangitis 17.29 16.73 10 45783 642 42574900
Immune-mediated gastritis 17.27 16.73 6 45787 112 42575430
Psoriatic arthropathy 17.26 16.73 3 45790 24964 42550578
Paronychia 17.14 16.73 22 45771 4233 42571309
Aphthous ulcer 17.04 16.73 26 45767 5875 42569667
Epidermolysis 16.97 16.73 9 45784 487 42575055
Immune-mediated thyroiditis 16.92 16.73 9 45784 490 42575052
Laryngeal leukoplakia 16.82 16.73 5 45788 55 42575487
Enostosis 16.73 16.73 4 45789 17 42575525

FDA Adverse Event Reporting System (Geriatric)

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
Malignant neoplasm progression 2765.93 16.39 1565 65785 173002 110348947
Pancytopenia 1560.05 16.39 1171 66179 208442 110313507
Disease progression 1110.64 16.39 1026 66324 243008 110278941
Myelosuppression 751.67 16.39 550 66800 93790 110428159
Anaemia 722.30 16.39 1235 66115 545851 109976098
Neutropenia 677.85 16.39 978 66372 373642 110148307
Tubulointerstitial nephritis 646.36 16.39 406 66944 53878 110468071
Thrombocytopenia 641.57 16.39 918 66432 347967 110173982
Interstitial lung disease 625.35 16.39 582 66768 138752 110383197
Pneumonitis 625.01 16.39 453 66897 76078 110445871
Therapy partial responder 575.80 16.39 329 67021 36732 110485217
Immune-mediated lung disease 460.07 16.39 158 67192 5145 110516804
Febrile neutropenia 444.61 16.39 736 66614 316031 110205918
Acute kidney injury 405.63 16.39 1067 66283 634363 109887586
Febrile bone marrow aplasia 383.09 16.39 195 67155 17270 110504679
Non-small cell lung cancer 373.72 16.39 151 67199 7784 110514165
Immune-mediated enterocolitis 324.67 16.39 147 67203 10038 110511911
Neoplasm progression 323.14 16.39 287 67063 64308 110457641
Metastases to central nervous system 318.44 16.39 189 67161 22628 110499321
Pseudocellulitis 313.55 16.39 69 67281 376 110521573
Mucosal inflammation 310.19 16.39 336 67014 95805 110426144
Hepatic cytolysis 304.42 16.39 259 67091 54794 110467155
Renal tubular necrosis 303.83 16.39 204 67146 30271 110491678
Colitis 284.59 16.39 331 67019 101992 110419957
Skin toxicity 283.23 16.39 140 67210 11643 110510306
Bone marrow failure 275.46 16.39 250 67100 57598 110464351
Drug resistance 271.13 16.39 245 67105 56129 110465820
Immune-mediated hepatic disorder 270.84 16.39 102 67248 4348 110517601
Haematotoxicity 249.08 16.39 157 67193 20925 110501024
Hypothyroidism 233.75 16.39 254 67096 72645 110449304
Hyperthyroidism 220.21 16.39 165 67185 29096 110492853
Acquired gene mutation 219.37 16.39 77 67273 2677 110519272
Pleural effusion 196.04 16.39 372 66978 177337 110344612
Pain 190.51 16.39 181 67169 954774 109567175
Leukopenia 190.16 16.39 332 67018 148459 110373490
Immune-mediated hepatitis 186.26 16.39 88 67262 6623 110515326
Rash maculo-papular 179.95 16.39 224 67126 73998 110447951
Neutrophil count decreased 175.98 16.39 286 67064 120655 110401294
Myocarditis 175.59 16.39 146 67204 29909 110492040
Joint swelling 174.24 16.39 30 67320 442815 110079134
Immune-mediated dermatitis 170.89 16.39 61 67289 2229 110519720
Lichenoid keratosis 166.85 16.39 80 67270 6222 110515727
Platelet count decreased 165.08 16.39 405 66945 230038 110291911
Arthralgia 163.44 16.39 141 67209 779491 109742458
Nephritis 159.86 16.39 77 67273 6049 110515900
Abdominal discomfort 158.68 16.39 25 67325 393833 110128116
Fall 158.67 16.39 85 67265 603397 109918552
EGFR gene mutation 155.00 16.39 41 67309 529 110521420
Synovitis 152.07 16.39 3 67347 274089 110247860
Nasopharyngitis 150.19 16.39 29 67321 394332 110127617
Pulmonary toxicity 149.18 16.39 107 67243 17639 110504310
Headache 144.57 16.39 196 67154 882181 109639768
Immune-mediated hypothyroidism 143.30 16.39 57 67293 2818 110519131
Nephropathy toxic 143.18 16.39 125 67225 27353 110494596
Hypertransaminasaemia 142.05 16.39 118 67232 24137 110497812
Musculoskeletal stiffness 141.27 16.39 7 67343 279815 110242134
Product dose omission issue 140.12 16.39 16 67334 321766 110200183
Tumour pseudoprogression 139.59 16.39 48 67302 1568 110520381
Decreased appetite 139.10 16.39 616 66734 475230 110046719
Pulmonary embolism 138.03 16.39 362 66988 214112 110307837
Peripheral swelling 137.40 16.39 38 67312 403996 110117953
Contraindicated product administered 136.60 16.39 3 67347 248264 110273685
Immune-mediated myocarditis 135.80 16.39 58 67292 3440 110518509
Renal impairment 134.72 16.39 331 67019 188114 110333835
Maternal exposure during pregnancy 133.22 16.39 5 67345 254878 110267071
Completed suicide 133.08 16.39 3 67347 242378 110279571
Subacute cutaneous lupus erythematosus 131.01 16.39 63 67287 4931 110517018
General physical health deterioration 130.71 16.39 559 66791 424736 110097213
Arthropathy 128.49 16.39 13 67337 287509 110234440
Weight increased 127.62 16.39 48 67302 419596 110102353
Sinusitis 126.10 16.39 16 67334 296672 110225277
Swelling 123.18 16.39 31 67319 351010 110170939
Pain in extremity 121.68 16.39 73 67277 487045 110034904
Renal failure 121.66 16.39 358 66992 226216 110295733
Wound 121.16 16.39 5 67345 234432 110287517
Glossodynia 120.91 16.39 3 67347 222001 110299948
Drug hypersensitivity 119.22 16.39 64 67286 454026 110067923
Lung adenocarcinoma 117.66 16.39 73 67277 9458 110512491
Therapeutic product effect decreased 117.55 16.39 8 67342 244308 110277641
Asthma 115.34 16.39 10 67340 250281 110271668
Hepatocellular injury 110.38 16.39 145 67205 50497 110471452
Muscle spasms 109 16.39 19 67331 278138 110243811
Hypophysitis 108.76 16.39 57 67293 5358 110516591
Septic shock 107.62 16.39 272 67078 157256 110364693
Pericardial effusion 106.84 16.39 152 67198 57065 110464884
Radiation pneumonitis 106.35 16.39 53 67297 4483 110517466
Metastases to meninges 105.91 16.39 55 67295 5073 110516876
Psoriatic arthropathy 105.87 16.39 3 67347 196758 110325191
Hepatotoxicity 104.76 16.39 159 67191 63241 110458708
Diarrhoea 103.31 16.39 1103 66247 1138402 109383547
Mobility decreased 100.41 16.39 13 67337 237409 110284540
Metastases to liver 99.19 16.39 115 67235 35271 110486678
Blood creatinine increased 98.17 16.39 289 67061 182600 110339349
Helicobacter infection 97.03 16.39 3 67347 181874 110340075
Immune-mediated renal disorder 96.13 16.39 30 67320 717 110521232
Paronychia 95.87 16.39 68 67282 11013 110510936
Contusion 95.80 16.39 14 67336 233347 110288602
Injury 94.29 16.39 3 67347 177262 110344687
Insomnia 92.90 16.39 52 67298 360538 110161411
Haemophagocytic lymphohistiocytosis 92.57 16.39 105 67245 31454 110490495
Respiratory failure 92.43 16.39 315 67035 215017 110306932
Depression 92.02 16.39 39 67311 317296 110204653
Drug intolerance 91.94 16.39 68 67282 406444 110115505
Injection site pain 91.24 16.39 4 67346 177918 110344031
Migraine 90.96 16.39 3 67347 171649 110350300
Drug abuse 90.94 16.39 4 67346 177407 110344542
Extremity necrosis 90.85 16.39 45 67305 3757 110518192
Osteoarthritis 90.79 16.39 5 67345 182618 110339331
Toxic epidermal necrolysis 90.53 16.39 140 67210 56587 110465362
Oesophagitis 90.17 16.39 99 67251 28616 110493333
Hepatic function abnormal 89.95 16.39 180 67170 89115 110432834
Dermatitis acneiform 89.79 16.39 69 67281 12626 110509323
Haemoptysis 89.51 16.39 158 67192 71196 110450753
Hypoaesthesia 87.37 16.39 41 67309 314182 110207767
Aplasia 86.45 16.39 56 67294 7817 110514132
Eastern Cooperative Oncology Group performance status worsened 85.68 16.39 40 67310 2929 110519020
Rheumatoid arthritis 85.00 16.39 38 67312 299575 110222374
Metastases to adrenals 84.16 16.39 33 67317 1570 110520379
Enteritis 83.81 16.39 79 67271 19077 110502872
Lung cancer metastatic 83.77 16.39 44 67306 4154 110517795
Discomfort 81.24 16.39 16 67334 214691 110307258
Systemic lupus erythematosus 80.85 16.39 27 67323 254311 110267638
Memory impairment 80.40 16.39 12 67338 196932 110325017
Renal tubular disorder 79.51 16.39 52 67298 7377 110514572
Radiotherapy 79.42 16.39 31 67319 1457 110520492
Exposure during pregnancy 79.03 16.39 6 67344 167418 110354531
Immune-mediated adverse reaction 78.84 16.39 32 67318 1668 110520281
Hypersensitivity 78.64 16.39 78 67272 403920 110118029
Osteonecrosis of jaw 75.92 16.39 118 67232 47899 110474050
Adrenocorticotropic hormone deficiency 74.34 16.39 33 67317 2149 110519800
Bicytopenia 74.26 16.39 48 67302 6676 110515273
Type 2 diabetes mellitus 74.22 16.39 10 67340 177222 110344727
Hepatitis 73.89 16.39 167 67183 89887 110432062
Muscle injury 72.75 16.39 3 67347 140804 110381145
Sleep disorder 72.69 16.39 16 67334 198628 110323321
Hypercreatininaemia 72.45 16.39 28 67322 1281 110520668
White blood cell count decreased 71.49 16.39 303 67047 229087 110292862
Gene mutation 71.46 16.39 37 67313 3392 110518557
Hypopituitarism 70.90 16.39 40 67310 4350 110517599
Hepatic enzyme increased 70.84 16.39 55 67295 320837 110201112
Blister 70.78 16.39 25 67325 227351 110294598
Secondary adrenocortical insufficiency 70.53 16.39 40 67310 4394 110517555
Dizziness 70.28 16.39 206 67144 697987 109823962
Lymphangiosis carcinomatosa 70.27 16.39 33 67317 2449 110519500
Impaired healing 69.69 16.39 17 67333 196700 110325249
Myasthenic syndrome 69.58 16.39 27 67323 1249 110520700
Intentional product use issue 69.44 16.39 32 67318 247874 110274075
Alopecia 69.19 16.39 72 67278 364681 110157268
Anxiety 69.04 16.39 65 67285 345013 110176936
Overdose 68.94 16.39 28 67322 233766 110288183
Urticaria 66.24 16.39 58 67292 318799 110203150
Performance status decreased 66.14 16.39 46 67304 7220 110514729
Wheezing 65.44 16.39 37 67313 255193 110266756
Malignant transformation 64.92 16.39 27 67323 1498 110520451
Erysipelas 64.83 16.39 58 67292 13100 110508849
Pneumothorax 63.32 16.39 92 67258 35193 110486756
Ischaemic stroke 63.28 16.39 100 67250 41163 110480786
Metastases to lung 63.04 16.39 74 67276 22989 110498960
Blood pressure increased 62.67 16.39 40 67310 258333 110263616
Dermo-hypodermitis 62.18 16.39 26 67324 1462 110520487
Cholangitis 61.41 16.39 62 67288 16273 110505676
Night sweats 59.98 16.39 6 67344 133977 110387972
Neutropenic colitis 59.60 16.39 45 67305 8020 110513929
Thrombophlebitis migrans 59.20 16.39 21 67329 753 110521196
Autoimmune hepatitis 59.00 16.39 58 67292 14746 110507203
Toxic skin eruption 58.74 16.39 78 67272 27437 110494512
Adrenal insufficiency 58.58 16.39 98 67252 42292 110479657
Lower respiratory tract infection 58.46 16.39 38 67312 243068 110278881
Immune-mediated arthritis 58.17 16.39 20 67330 653 110521296
Immune-mediated adrenal insuficiency 57.70 16.39 26 67324 1754 110520195
Malignant pleural effusion 57.34 16.39 34 67316 4059 110517890
Metastases to pleura 57.09 16.39 27 67323 2036 110519913
Intentional product misuse 56.85 16.39 7 67343 132897 110389052
Obesity 56.66 16.39 3 67347 113348 110408601
Immune-mediated cholangitis 56.48 16.39 21 67329 863 110521086
Asthenia 56.26 16.39 654 66696 688345 109833604
Scleroderma-like reaction 55.38 16.39 15 67335 213 110521736
Non-small cell lung cancer metastatic 54.41 16.39 23 67327 1329 110520620
Feeling abnormal 54.33 16.39 21 67329 180690 110341259
Gait inability 54.10 16.39 9 67341 136367 110385582
Pyrexia 53.91 16.39 806 66544 897459 109624490
Tremor 53.75 16.39 28 67322 202204 110319745
Loss of personal independence in daily activities 53.06 16.39 13 67337 150007 110371942
Folliculitis 51.20 16.39 19 67331 167634 110354315
Cholestasis 51.10 16.39 118 67232 64400 110457549
Suicide attempt 50.86 16.39 3 67347 103391 110418558
Metastases to bone 50.86 16.39 78 67272 31294 110490655
Gastrooesophageal reflux disease 50.75 16.39 23 67327 179953 110341996
Gastrointestinal toxicity 50.74 16.39 47 67303 11101 110510848
Neutropenic sepsis 50.63 16.39 77 67273 30669 110491280
C-reactive protein abnormal 50.47 16.39 9 67341 129686 110392263
Purpura 50.32 16.39 68 67282 24320 110497629
Metastasis 50.03 16.39 41 67309 8226 110513723
Ill-defined disorder 49.23 16.39 17 67333 156836 110365113
Immune-mediated pancreatitis 49.21 16.39 18 67332 706 110521243
Transaminases increased 49.18 16.39 115 67235 63275 110458674
Abdominal pain upper 48.89 16.39 86 67264 349025 110172924
Melanoderma 48.67 16.39 16 67334 454 110521495
Hiccups 48.66 16.39 49 67301 12820 110509129
Peritonitis 48.60 16.39 78 67272 32529 110489420
Bradycardia 48.56 16.39 17 67333 155500 110366449
Small intestinal perforation 47.74 16.39 31 67319 4345 110517604
Sepsis 47.66 16.39 352 66998 326994 110194955
Gait disturbance 47.23 16.39 60 67290 278148 110243801
Dry mouth 47.07 16.39 32 67318 199916 110322033
Immune thrombocytopenia 46.84 16.39 63 67287 22431 110499518
Confusional state 46.58 16.39 139 67211 468541 110053408
Systemic scleroderma 46.11 16.39 23 67327 1949 110520000
Autoimmune colitis 45.97 16.39 23 67327 1962 110519987
Nausea 45.44 16.39 1027 66323 1234663 109287286
Suicidal ideation 45.39 16.39 3 67347 93934 110428015
Scleroedema 45.35 16.39 12 67338 155 110521794
Paraneoplastic syndrome 44.77 16.39 20 67330 1322 110520627
Dyspepsia 44.37 16.39 31 67319 190934 110331015
Wound infection 44.02 16.39 4 67346 96461 110425488
Cytokine release syndrome 43.47 16.39 117 67233 70189 110451760
Peripheral ischaemia 43.47 16.39 43 67307 11015 110510934
Vomiting 43.44 16.39 787 66563 909888 109612061
Non-small cell lung cancer recurrent 42.63 16.39 12 67338 198 110521751
Nasal congestion 42.47 16.39 5 67345 98277 110423672
Stasis dermatitis 41.86 16.39 21 67329 1801 110520148
Amnesia 41.71 16.39 7 67343 105401 110416548
Lymphadenopathy mediastinal 41.42 16.39 31 67319 5453 110516496
Carcinoembryonic antigen increased 40.98 16.39 24 67326 2800 110519149
Tumour associated fever 40.98 16.39 18 67332 1143 110520806
Hypersensitivity pneumonitis 40.29 16.39 30 67320 5235 110516714
Hypokalaemia 40.12 16.39 218 67132 182230 110339719
Large intestine perforation 39.98 16.39 50 67300 16579 110505370
Peripheral venous disease 39.73 16.39 3 67347 84114 110437835
Dermatitis bullous 39.45 16.39 51 67299 17478 110504471
Enterocolitis 39.35 16.39 53 67297 18896 110503053
Hypertension 38.31 16.39 170 67180 509914 110012035
Blood thyroid stimulating hormone decreased 37.84 16.39 33 67317 7206 110514743
Injection site reaction 37.34 16.39 5 67345 89065 110432884
Autoimmune lung disease 37.28 16.39 11 67339 216 110521733
Ototoxicity 37.24 16.39 26 67324 4105 110517844
Tracheal fistula 37.00 16.39 11 67339 222 110521727
Gamma-glutamyltransferase increased 36.87 16.39 101 67249 61208 110460741
Pericarditis malignant 36.67 16.39 9 67341 84 110521865
Somnolence 36.67 16.39 79 67271 297370 110224579
Hospitalisation 36.02 16.39 21 67329 142472 110379477
Dehydration 35.91 16.39 292 67058 279219 110242730
Pneumonia 35.77 16.39 740 66610 875974 109645975
Heteroplasia 34.89 16.39 7 67343 22 110521927
Microvascular coronary artery disease 34.89 16.39 12 67338 392 110521557
Treatment failure 34.70 16.39 73 67277 277161 110244788
Drug interaction 34.44 16.39 172 67178 500011 110021938
Epistaxis 34.42 16.39 164 67186 130208 110391741
Cytopenia 34.34 16.39 64 67286 30052 110491897
Lung adenocarcinoma recurrent 34.32 16.39 9 67341 112 110521837
Visceral leishmaniasis 33.89 16.39 18 67332 1738 110520211
Drug eruption 33.88 16.39 90 67260 53569 110468380
Red blood cell sedimentation rate increased 33.79 16.39 4 67346 78298 110443651
Immune-mediated nephritis 33.71 16.39 16 67334 1216 110520733
Autoimmune nephritis 33.44 16.39 14 67336 790 110521159
Hyperhidrosis 33.25 16.39 39 67311 187259 110334690
Immune-mediated gastritis 32.97 16.39 11 67339 327 110521622
Hyperphosphaturia 32.96 16.39 9 67341 132 110521817
Skin hyperpigmentation 32.68 16.39 33 67317 8663 110513286
Proteinuria 32.58 16.39 74 67276 39944 110482005
Immune-mediated oesophagitis 32.47 16.39 8 67342 76 110521873
Hypoalbuminaemia 32.32 16.39 61 67289 28913 110493036
Tumour hyperprogression 32.11 16.39 11 67339 355 110521594
Endocrine toxicity 32.10 16.39 8 67342 80 110521869
Adenocarcinoma 31.89 16.39 24 67326 4256 110517693
Erysipeloid 31.84 16.39 6 67344 12 110521937
Myositis 31.65 16.39 63 67287 31053 110490896
Type 1 diabetes mellitus 31.59 16.39 33 67317 9014 110512935
Fulminant type 1 diabetes mellitus 31.47 16.39 19 67331 2344 110519605
Bronchostenosis 31.36 16.39 14 67336 924 110521025
Influenza 31.34 16.39 34 67316 169067 110352882
Neck pain 31.33 16.39 18 67332 123112 110398837
Immune-mediated encephalitis 31.18 16.39 15 67335 1175 110520774
Nephrogenic diabetes insipidus 30.87 16.39 19 67331 2426 110519523
Arthritis 30.72 16.39 34 67316 167552 110354397
Agranulocytosis 30.66 16.39 95 67255 61665 110460284
Thyroiditis 30.47 16.39 28 67322 6545 110515404
Hallucination 30.13 16.39 12 67338 101420 110420529
Rash 29.97 16.39 682 66668 820282 109701667
Cardiac failure congestive 29.52 16.39 29 67321 150971 110370978
Illness 29.29 16.39 7 67343 82164 110439785
Immune-mediated thyroiditis 29.28 16.39 14 67336 1082 110520867
Metastatic neoplasm 29.16 16.39 26 67324 5847 110516102
Medication error 28.87 16.39 14 67336 105352 110416597
Inflammation 28.51 16.39 46 67304 193192 110328757
Hypoglycaemia 28.10 16.39 18 67332 116086 110405863
Pericarditis 28.00 16.39 57 67293 219057 110302892
Hepatic cirrhosis 27.87 16.39 4 67346 67622 110454327
Death 27.85 16.39 588 66762 698281 109823668
Immune-mediated cystitis 27.72 16.39 8 67342 145 110521804
Heart rate decreased 27.69 16.39 8 67342 82748 110439201
Frequent bowel movements 27.67 16.39 5 67345 71385 110450564
Pulmonary radiation injury 27.65 16.39 7 67343 75 110521874
Lactic acidosis 27.53 16.39 11 67339 92800 110429149
Acute coronary syndrome 27.47 16.39 50 67300 23062 110498887
Psoriasis 27.24 16.39 27 67323 139966 110381983
Cystitis 26.99 16.39 4 67346 66032 110455917
Oral fungal infection 26.77 16.39 22 67328 4430 110517519
Paraesthesia 26.73 16.39 83 67267 276438 110245511
Immune-mediated hyperthyroidism 26.33 16.39 11 67339 617 110521332
Jaw operation 26.32 16.39 12 67338 832 110521117
Radiotherapy to bone 26.21 16.39 5 67345 11 110521938
Metastases to peritoneum 26.21 16.39 24 67326 5586 110516363
Radiation necrosis 26.19 16.39 12 67338 842 110521107
Venous thrombosis 26.14 16.39 29 67321 8476 110513473
Adrenal disorder 25.97 16.39 17 67333 2415 110519534
Tumour necrosis 25.95 16.39 17 67333 2419 110519530
Radiotherapy to lung 25.91 16.39 5 67345 12 110521937
Sarcomatoid carcinoma 25.85 16.39 6 67344 43 110521906
Malaise 25.83 16.39 273 67077 671546 109850403
Pancreatic toxicity 25.80 16.39 7 67343 100 110521849
Immune-mediated cytopenia 25.66 16.39 9 67341 312 110521637
Abdominal distension 25.54 16.39 42 67308 175061 110346888
Agitation 25.41 16.39 19 67331 113032 110408917
Aortic thrombosis 25.14 16.39 16 67334 2167 110519782
Tracheo-oesophageal fistula 25.05 16.39 11 67339 698 110521251
Autoimmune hypothyroidism 25.01 16.39 10 67340 501 110521448
Coma 24.99 16.39 21 67329 117848 110404101
Papillary cystadenoma lymphomatosum 24.92 16.39 8 67342 210 110521739
Hypocalcaemia 24.90 16.39 92 67258 65274 110456675
Wrong technique in product usage process 24.87 16.39 11 67339 87337 110434612
Mixed deafness 24.86 16.39 5 67345 16 110521933
Blood phosphorus abnormal 24.85 16.39 9 67341 343 110521606
Sedation 24.71 16.39 6 67344 69677 110452272
Condition aggravated 24.59 16.39 308 67042 734528 109787421
Haemolytic anaemia 24.53 16.39 45 67305 20875 110501074
Autoimmune disorder 24.51 16.39 5 67345 65478 110456471
Bronchitis 24.49 16.39 36 67314 156996 110364953
Burning sensation 24.46 16.39 6 67344 69206 110452743
Pulmonary artery thrombosis 24.27 16.39 14 67336 1588 110520361
Immune-mediated myositis 24.21 16.39 24 67326 6162 110515787
Autoimmune haemolytic anaemia 24.18 16.39 31 67319 10536 110511413
Keratitis 24.02 16.39 22 67328 5122 110516827
Gastrointestinal perforation 23.91 16.39 26 67324 7430 110514519
Swollen tongue 23.90 16.39 4 67346 60358 110461591
Necrotising myositis 23.87 16.39 15 67335 1987 110519962
Cancer fatigue 23.82 16.39 9 67341 387 110521562
Superior vena cava syndrome 23.80 16.39 13 67337 1328 110520621
Posterior reversible encephalopathy syndrome 23.65 16.39 59 67291 33802 110488147
Immune-mediated endocrinopathy 23.65 16.39 7 67343 139 110521810
Hepatitis cholestatic 23.46 16.39 40 67310 17526 110504423
Intestinal perforation 23.25 16.39 44 67306 20900 110501049
Hepatitis toxic 23.23 16.39 23 67327 5898 110516051
Oesophagobronchial fistula 23.13 16.39 8 67342 266 110521683
Musculoskeletal pain 23.05 16.39 48 67302 182975 110338974
Hypomagnesaemia 23.02 16.39 85 67265 60285 110461664
Nephrolithiasis 22.90 16.39 6 67344 66206 110455743
Disseminated intravascular coagulation 22.85 16.39 66 67284 41220 110480729
Oral papule 22.85 16.39 4 67346 4 110521945
Encephalitis 22.70 16.39 41 67309 18798 110503151
Cardiac disorder 22.69 16.39 9 67341 76271 110445678
Cataract 22.65 16.39 10 67340 79475 110442474
Granulocyte count decreased 22.57 16.39 19 67331 3955 110517994
BRAF V600E mutation positive 22.43 16.39 6 67344 81 110521868
Cancer pain 22.40 16.39 24 67326 6748 110515201
Prescribed underdose 22.36 16.39 6 67344 65168 110456781
Hyperpyrexia 22.23 16.39 26 67324 8043 110513906
Dacryostenosis acquired 22.20 16.39 10 67340 674 110521275
Flagellate dermatitis 22.16 16.39 8 67342 302 110521647
Dermatitis 22.13 16.39 51 67299 27786 110494163
Hyperamylasaemia 22.12 16.39 12 67338 1209 110520740
Back pain 22.00 16.39 134 67216 370862 110151087
Urinary tract infection 21.98 16.39 113 67237 326169 110195780
Cardiotoxicity 21.96 16.39 38 67312 16843 110505106
Blood thyroid stimulating hormone increased 21.96 16.39 32 67318 12269 110509680
Bacterial prostatitis 21.91 16.39 6 67344 89 110521860
Blood creatine phosphokinase abnormal 21.86 16.39 10 67340 699 110521250
Erythema multiforme 21.80 16.39 43 67307 21054 110500895
Embolism 21.63 16.39 37 67313 16252 110505697
Lung neoplasm malignant 21.60 16.39 57 67293 33785 110488164
Thrombotic thrombocytopenic purpura 21.43 16.39 24 67326 7087 110514862
Dyskinesia 21.30 16.39 3 67347 51443 110470506
Product prescribing error 21.24 16.39 3 67347 51328 110470621
Metastases to the mediastinum 20.79 16.39 10 67340 783 110521166
Necrotic lymphadenopathy 20.76 16.39 7 67343 215 110521734
Pneumonia bacterial 20.76 16.39 48 67302 26213 110495736
Radiation neuropathy 20.61 16.39 4 67346 10 110521939
Eye pain 20.56 16.39 3 67347 50096 110471853
Heart rate increased 20.51 16.39 35 67315 143799 110378150
Cutaneous lupus erythematosus 20.48 16.39 17 67333 3471 110518478
Stevens-Johnson syndrome 20.43 16.39 69 67281 46832 110475117
Rhabdomyolysis 20.39 16.39 26 67324 120375 110401574
Autoimmune dermatitis 20.37 16.39 7 67343 228 110521721
Bronchogram abnormal 20.34 16.39 4 67346 11 110521938
Secondary hypertension 20.16 16.39 9 67341 594 110521355
Post procedural oedema 19.96 16.39 6 67344 126 110521823
Lung consolidation 19.80 16.39 28 67322 10448 110511501
Organising pneumonia 19.77 16.39 33 67317 14210 110507739
Fluid retention 19.75 16.39 17 67333 94290 110427659
Epidermolysis 19.75 16.39 11 67339 1167 110520782
Pneumocystis jirovecii pneumonia 19.62 16.39 64 67286 42671 110479278
Laryngeal leukoplakia 19.55 16.39 5 67345 56 110521893
Rash pustular 19.54 16.39 31 67319 12798 110509151
Full blood count abnormal 19.54 16.39 5 67345 56047 110465902
Autoimmune myocarditis 19.50 16.39 9 67341 642 110521307
Skin disorder 19.47 16.39 64 67286 42849 110479100
Plasma cell myeloma 19.43 16.39 7 67343 62929 110459020
Aspartate aminotransferase increased 19.41 16.39 165 67185 159771 110362178
Spinal cord abscess 19.39 16.39 9 67341 650 110521299
Troponin abnormal 19.36 16.39 6 67344 140 110521809
Small cell lung cancer 19.32 16.39 16 67334 3256 110518693
Lymphangitis 19.30 16.39 12 67338 1560 110520389
Diabetic ketoacidotic hyperglycaemic coma 19.20 16.39 7 67343 272 110521677
Genital tract inflammation 19.05 16.39 6 67344 148 110521801
Incorrect dose administered 19.02 16.39 21 67329 103620 110418329
Unmasking of previously unidentified disease 19.00 16.39 15 67335 2853 110519096
Kidney fibrosis 18.99 16.39 18 67332 4374 110517575
Lymphocytic hypophysitis 18.96 16.39 9 67341 684 110521265
Alanine aminotransferase increased 18.94 16.39 183 67167 183590 110338359
Periorbital oedema 18.90 16.39 27 67323 10165 110511784
Visual impairment 18.90 16.39 33 67317 134395 110387554
Immune-mediated hypophysitis 18.78 16.39 10 67340 971 110520978
Acute generalised exanthematous pustulosis 18.69 16.39 41 67309 21623 110500326
Metastases to lymph nodes 18.47 16.39 33 67317 14999 110506950
Accidental exposure to product 18.34 16.39 4 67346 50004 110471945
Joint stiffness 18.32 16.39 9 67341 67234 110454715
Onychomadesis 18.13 16.39 3 67347 45660 110476289
Cerebral infarction 18.13 16.39 71 67279 51767 110470182
Treatment noncompliance 18.10 16.39 11 67339 72979 110448970
Ear pain 18.08 16.39 5 67345 53221 110468728
Cholangitis sclerosing 18.06 16.39 16 67334 3566 110518383
Acquired tracheo-oesophageal fistula 18.06 16.39 6 67344 176 110521773
Electrocardiogram QT prolonged 17.96 16.39 24 67326 108936 110413013
Renal tubular injury 17.94 16.39 15 67335 3093 110518856
Basal cell carcinoma 17.92 16.39 3 67347 45267 110476682
Hepatitis acute 17.90 16.39 37 67313 18729 110503220
Idiopathic interstitial pneumonia 17.90 16.39 9 67341 776 110521173
Upper respiratory tract infection 17.78 16.39 33 67317 131295 110390654
Toxicity to various agents 17.76 16.39 197 67153 480358 110041591
Second primary malignancy 17.68 16.39 36 67314 18032 110503917
Hip arthroplasty 17.59 16.39 6 67344 55807 110466142
Aggression 17.59 16.39 7 67343 59203 110462746
Lacrimation disorder 17.57 16.39 4 67346 26 110521923
Pulmonary resection 17.51 16.39 6 67344 194 110521755
Embolism arterial 17.46 16.39 12 67338 1847 110520102
HRD gene mutation assay positive 17.32 16.39 4 67346 28 110521921
Duodenal perforation 17.31 16.39 14 67336 2756 110519193
Blood corticotrophin decreased 17.22 16.39 9 67341 841 110521108
Tracheobronchitis viral 17.19 16.39 4 67346 29 110521920
Radiotherapy to adrenal gland 17.14 16.39 3 67347 3 110521946
Glucocorticoid deficiency 17.03 16.39 10 67340 1172 110520777
Embolism venous 16.96 16.39 18 67332 5005 110516944
Mouth ulceration 16.89 16.39 66 67284 48072 110473877
Superinfection bacterial 16.87 16.39 13 67337 2388 110519561
Superior mesenteric artery syndrome 16.87 16.39 6 67344 217 110521732
Large intestine infection 16.79 16.39 17 67333 4475 110517474
Cardiac tamponade 16.78 16.39 27 67323 11280 110510669
Xeroderma 16.77 16.39 8 67342 615 110521334
Primary adrenal insufficiency 16.76 16.39 8 67342 616 110521333
Diverticular perforation 16.70 16.39 20 67330 6342 110515607
Autoimmune pericarditis 16.68 16.39 5 67345 104 110521845
Lung lobectomy 16.58 16.39 6 67344 228 110521721
Nephrosclerosis 16.56 16.39 12 67338 2009 110519940
Cancer with a high tumour mutational burden 16.53 16.39 4 67346 35 110521914
Polyarthritis 16.48 16.39 36 67314 18927 110503022
Blood glucose increased 16.47 16.39 35 67315 132461 110389488

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01BA04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Folic acid analogues
FDA MoA N0000000111 Folic Acid Metabolism Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D005493 Folic Acid Antagonists
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
FDA EPC N0000175584 Folate Analog Metabolic Inhibitor
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50683 EC 1.5.1.3 (dihydrofolate reductase) inhibitor
CHEBI has role CHEBI:63720 EC 2.1.1.45 (thymidylate synthase) inhibitor
CHEBI has role CHEBI:63721 EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

L01BA Folic acid analogues 3 drugs
methotrexatepralatrexateraltitrexed

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908
Malignant mesothelioma of pleura indication 254645002 DOID:7474
Kidney disease contraindication 90708001 DOID:557
Impaired renal function disorder contraindication 197663003
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Concomitant yellow fever vaccine contraindication 871717007




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.34 acidic
pKa2 5.15 acidic
pKa3 9.45 acidic
pKa4 13.09 acidic
pKa5 3.95 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
500MG/20ML (25MG/ML) PEMFEXY EAGLE PHARMS N209472 Feb. 8, 2020 RX SOLUTION INTRAVENOUS 12115164 Feb. 19, 2036 FOR USE IN THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC)
500MG/20ML (25MG/ML) PEMFEXY EAGLE PHARMS N209472 Feb. 8, 2020 RX SOLUTION INTRAVENOUS 12115164 Feb. 19, 2036 FOR USE IN THE TREATMENT OF PATIENTS WITH MALIGNANT PLEURAL MESOTHELIOMA
500MG/20ML (25MG/ML) PEMFEXY EAGLE PHARMS N209472 Feb. 8, 2020 RX SOLUTION INTRAVENOUS 12115164 Feb. 19, 2036 FOR USE IN THE TREATMENT OF PATIENTS WITH MALIGNANT PLEURAL MESOTHELIOMA AND/OR LOCALLY ADVANCED OR METASTATIC NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC)

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Dihydrofolate reductase Enzyme INHIBITOR IC50 5.18 WOMBAT-PK CHEMBL
Thymidylate synthase Enzyme INHIBITOR IC50 6.47 WOMBAT-PK CHEMBL
Trifunctional purine biosynthetic protein adenosine-3 Enzyme INHIBITOR Ki 6.42 CHEMBL DRUG LABEL
Folylpolyglutamate synthase, mitochondrial Enzyme WOMBAT-PK
Serine hydroxymethyltransferase, cytosolic Enzyme Kd 4.77 CHEMBL
Tyrosine-protein kinase FRK Kinase IC50 7.38 CHEMBL
Folate receptor beta Membrane receptor IC50 7.22 CHEMBL
Proton-coupled folate transporter Transporter Ki 7.03 CHEMBL
Folate transporter 1 Transporter IC50 6.86 CHEMBL
Bifunctional purine biosynthesis protein PURH Enzyme Ki 6.06 CHEMBL
Folate receptor alpha Membrane receptor IC50 7.38 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme IC50 6.37 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.64 CHEMBL
Thymidylate synthase Enzyme IC50 4.82 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.64 CHEMBL
Thymidylate synthase Enzyme Ki 6.47 CHEMBL
Thymidylate synthase Enzyme IC50 4.70 CHEMBL
Thymidylate synthase Enzyme Ki 6.26 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.64 CHEMBL
Thymidylate synthase Enzyme IC50 5.96 CHEMBL
Thymidylate synthase (EC 2.1.1.45) (TS) (TSase) Enzyme IC50 4.12 CHEMBL
Dihydrofolate reductase Enzyme Ki 6.25 CHEMBL
Trifunctional purine biosynthetic protein adenosine-3 Enzyme INHIBITOR Ki 5.03 IUPHAR

External reference:

IDSource
4021417 VUID
N0000148831 NUI
D03828 KEGG_DRUG
150399-23-8 SECONDARY_CAS_RN
4021417 VANDF
C0210657 UMLSCUI
CHEBI:63616 CHEBI
4DW PDB_CHEM_ID
CHEMBL225072 ChEMBL_ID
CHEMBL5315053 ChEMBL_ID
CHEMBL2360464 ChEMBL_ID
D000068437 MESH_DESCRIPTOR_UI
DB00642 DRUGBANK_ID
135410875 PUBCHEM_CID
6837 IUPHAR_LIGAND_ID
7675 INN_ID
04Q9AIZ7NO UNII
1666923 RXNORM
17856 MMSL
238966 MMSL
32871 MMSL
48646 MMSL
d05047 MMSL
008494 NDDF
008495 NDDF
409159000 SNOMEDCT_US
411089001 SNOMEDCT_US
735172002 SNOMEDCT_US
357166-29-1 SECONDARY_CAS_RN
04Q9AIZ7NO INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Alimta HUMAN PRESCRIPTION DRUG LABEL 1 0002-7623 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS NDA 32 sections
Alimta HUMAN PRESCRIPTION DRUG LABEL 1 0002-7640 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS NDA 32 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-0004 INJECTION, SOLUTION, CONCENTRATE 1 g INTRAVENOUS NDA 30 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-0020 INJECTION, SOLUTION, CONCENTRATE 100 mg INTRAVENOUS NDA 30 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-0021 INJECTION, SOLUTION, CONCENTRATE 500 mg INTRAVENOUS NDA 30 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-1045 INJECTION, SOLUTION, CONCENTRATE 100 mg INTRAVENOUS NDA 32 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-1045 INJECTION, SOLUTION, CONCENTRATE 100 mg INTRAVENOUS NDA 32 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-2188 INJECTION, SOLUTION, CONCENTRATE 500 mg INTRAVENOUS NDA 32 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-2188 INJECTION, SOLUTION, CONCENTRATE 500 mg INTRAVENOUS NDA 32 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-3532 INJECTION, SOLUTION, CONCENTRATE 1 g INTRAVENOUS NDA 32 sections
PEMETREXED HUMAN PRESCRIPTION DRUG LABEL 1 0409-3532 INJECTION, SOLUTION, CONCENTRATE 1 g INTRAVENOUS NDA 32 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 0781-3518 INJECTION, SOLUTION 100 mg INTRAVENOUS NDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 0781-3519 INJECTION, SOLUTION 500 mg INTRAVENOUS NDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 0781-3520 INJECTION, SOLUTION 1000 mg INTRAVENOUS NDA 27 sections
Pemetrexed disodium HUMAN PRESCRIPTION DRUG LABEL 1 43598-370 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1 g INTRAVENOUS ANDA 27 sections
Pemetrexed disodium HUMAN PRESCRIPTION DRUG LABEL 1 43598-386 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 27 sections
Pemetrexed disodium HUMAN PRESCRIPTION DRUG LABEL 1 43598-387 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-134 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 30 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-450 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 30 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-621 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 750 mg INTRAVENOUS ANDA 30 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-622 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1 g INTRAVENOUS ANDA 30 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 68001-543 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 68001-544 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 68001-545 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 750 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 68001-546 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1000 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70069-834 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 28 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70069-835 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 28 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70710-1654 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 24 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70710-1655 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 24 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70710-1674 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1000 mg INTRAVENOUS ANDA 24 sections