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

Stem definitionDrug idCAS RN
cyclin dependant kinase inhibitors 4941 571190-30-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • palbociclib
  • palbociclib isethionate
  • ibrance
  • PD-0332991
  • PD-0332991-0054
  • PF-00080665-73
  • PD 0332991
Palbociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways which lead to cellular proliferation. In vitro, palbociclib reduced cellular proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma (Rb) protein phosphorylation resulting in reduced E2F expression and signaling, and increased growth arrest compared to treatment with each drug alone. In vitro treatment of ER-positive breast cancer cell lines with the combination of palbociclib and antiestrogens led to increased cell senescence compared to each drug alone, which was sustained for up to 6 days following palbociclib removal and was greater if antiestrogen treatment was continued. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared to each drug alone.
  • Molecular weight: 447.54
  • Formula: C24H29N7O2
  • CLOGP: 2.48
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 2
  • TPSA: 103.35
  • ALOGS: -4.41
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
94 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.569 Moderate 0.76
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.603 Moderate 0.76
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 16.982 10^-6 cm/s Moderate 0.76
dh-clint Dog hepatocyte intrinsic clearance 3.673 uL/min/10^6 cells Moderate 0.76
dppb Dog plasma protein binding (% unbound) 29.760 % Moderate 0.76
fcs-ppb Fetal calf serum protein binding (% unbound) 46.720 % Moderate 0.76
herg hERG pIC50 5.067 pIC50 Moderate 0.76
hh-clint Human hepatocyte intrinsic clearance 3.420 uL/min/10^6 cells Moderate 0.76
hlm-clint Human liver microsomal intrinsic clearance 11.722 uL/min/mg protein Moderate 0.76
hppb Human plasma protein binding (% unbound) 28.620 % Moderate 0.76
kinase-safety-class AAK1,ABL1,ABL2,ACVR2A,ACVR2B,ACVRL1,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK3,CDK4,CDK5,CDK6,CDK7,CDK9,CHEK1,CHEK2,CLK1,CLK2,CLK4,CSF1R,CSNK2A2,DDR1,DYRK1A,DYRK1B,DYRK2,DYRK3,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FYN,GAK,GRK2,GSK3B,HASPIN,HIPK2,IGF1R,INSR,INSRR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK7,MAPK9,MARK1,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,MTOR,MYLK,NTRK1,NTRK2,NUAK1,PAK2,PAK4,PDGFRB,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM1,PIM2,PIM3,PLK1,PLK2,PLK3,PLK4,PRKAA1,PRKAA2,PRKCD,PRKDC,PTK2,RET,RIPK3,RPS6KA1,SIK2,SIK3,SRC,STK17A,STK33,STK4,SYK,TBK1,TEK,TGFBR1,TNIK,TNK1,TTK,TYRO3,ULK1,ULK2,YES1 146
kinase-selectivity-class ACVR2B,ALK,AURKB,AURKC,AXL,BLK,BRAF,CAMK2A,CAMK2B,CAMK2D,CDK16,CDK4,CDK6,CDK9,CHEK1,CLK2,CLK4,CSF1R,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FGFR1,FLT3,GAK,INSR,IRAK1,IRAK3,JAK1,JAK2,KIT,LCK,LRRK2,MAP3K10,MAP3K11,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK7,MARK4,MELK,MET,NTRK1,PAK4,PDK1,PDK4,PIK3CA,PIM3,PLK3,PLK4,PRKAA1,PRKAA2,PRKCD,PRKDC,RET,SIK2,SIK3,SRC,STK16,STK33,SYK,TEK,TNIK,TTK,TYRO3,ULK1,ULK2 70
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 6.266 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 15.136 Moderate 0.76
mh-clint Mouse hepatocyte intrinsic clearance 13.646 Moderate 0.76
mppb Mouse plasma protein binding (% unbound) 18.360 Moderate 0.76
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 44.771 Moderate 0.76
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 51.900 % Moderate 0.76
rat-kpuu-brain Rat brain Kpuu 0.027 % High 1
rh-clint Rat hepatocyte intrinsic clearance 8.913 uL/min/10^6 cells Moderate 0.76
rh-fuinc Rat hepatocyte fraction unbound in incubation 48.790 % Moderate 0.76
rppb Rat plasma protein binding (% unbound) 17.120 % Moderate 0.76
solubility-dd Solubility at pH 7.4 in DMSO 89.743 uM Moderate 0.76

Approvals:

DateAgencyCompanyOrphan
Sept. 27, 2017 PMDA Pfizer Japan Inc
Nov. 9, 2016 EMA Pfizer Limited
Feb. 3, 2015 FDA PFIZER INC

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
Neoplasm progression 17039.74 17.07 5356 166584 39130 90417377
White blood cell count decreased 12668.42 17.07 6205 165735 160904 90295603
Neutropenia 6702.91 17.07 4553 167387 220351 90236156
Fatigue 6602.33 17.07 9374 162566 1144649 89311858
Full blood count abnormal 2184.91 17.07 1162 170778 35435 90421072
Alopecia 2117.35 17.07 3541 168399 491530 89964977
Full blood count decreased 2045.76 17.07 1038 170902 28651 90427856
Neutrophil count decreased 1977.19 17.07 1387 170553 70145 90386362
Nausea 1827.84 17.07 5406 166534 1104910 89351597
Hot flush 1710.49 17.07 1182 170758 58306 90398201
Red blood cell count decreased 1451.27 17.07 971 170969 45380 90411127
Malignant neoplasm progression 1364.92 17.07 1323 170617 105547 90350960
Death 1169.70 17.07 2633 169307 453918 90002589
Disease progression 1095.76 17.07 1416 170524 155199 90301308
Tumour marker increased 1095.20 17.07 413 171527 5394 90451113
Drug ineffective 1063.36 17.07 662 171278 1383636 89072871
Metastases to bone 1008.08 17.07 619 171321 24886 90431621
Platelet count decreased 893.77 17.07 1197 170743 135772 90320735
Decreased appetite 880.06 17.07 2096 169844 374444 90082063
Stomatitis 871.13 17.07 1730 170210 272968 90183539
Constipation 802.86 17.07 1693 170247 278702 90177805
Leukopenia 772.84 17.07 954 170986 99756 90356751
Infusion related reaction 747.75 17.07 8 171932 416772 90039735
Diarrhoea 744.98 17.07 3630 168310 935560 89520947
Bone pain 717.87 17.07 728 171212 61255 90395252
Product dose omission issue 710.58 17.07 1651 170289 290036 90166471
Maternal exposure during pregnancy 650.04 17.07 6 171934 360057 90096450
Second primary malignancy 634.39 17.07 335 171605 10043 90446464
Epistaxis 629.99 17.07 792 171148 84333 90372174
Rheumatoid arthritis 613.09 17.07 16 171924 362598 90093909
Oral pain 602.08 17.07 498 171442 32185 90424322
Dry skin 594.61 17.07 783 171157 87290 90369217
Contraindicated product administered 584.34 17.07 4 171936 320135 90136372
Systemic lupus erythematosus 576.75 17.07 26 171914 361870 90094637
Bone marrow failure 554.38 17.07 472 171468 31749 90424758
Hand deformity 544.47 17.07 3 171937 296359 90160148
Metastases to liver 518.27 17.07 433 171507 28374 90428133
Pericarditis 485.13 17.07 5 171935 270146 90186361
Product dose omission in error 478.03 17.07 359 171581 20144 90436363
Arthropathy 463.02 17.07 71 171869 366171 90090336
Joint swelling 454.97 17.07 193 171747 503107 89953400
Asthenia 449.28 17.07 2102 169838 531649 89924858
Therapeutic product effect decreased 448.59 17.07 18 171922 277553 90178954
Drug hypersensitivity 415.42 17.07 180 171760 463429 89993078
Psoriatic arthropathy 410.99 17.07 4 171936 228331 90228176
Swelling 404.53 17.07 145 171795 418913 90037594
Wound 401.08 17.07 51 171889 302929 90153578
Thrombocytopenia 387.93 17.07 1067 170873 207658 90248849
Neuropathy peripheral 377.34 17.07 815 171125 136155 90320352
Folliculitis 370.54 17.07 3 171937 204350 90252157
Therapy cessation 361.83 17.07 394 171546 35967 90420540
Lower respiratory tract infection 347.20 17.07 36 171904 250623 90205884
Hypersensitivity 328.42 17.07 231 171709 454446 90002061
Irritable bowel syndrome 323.57 17.07 17 171923 207431 90249076
Anaemia 319.76 17.07 1421 170519 351381 90105126
Osteonecrosis of jaw 318.50 17.07 382 171558 38721 90417786
Breast cancer metastatic 313.44 17.07 247 171693 14885 90441622
Fibromyalgia 306.40 17.07 22 171918 206247 90250260
Intentional product use issue 303.35 17.07 30 171910 216862 90239645
Injury 302.15 17.07 18 171922 197331 90259176
Cytopenia 300.90 17.07 256 171684 17193 90439314
Drug intolerance 296.98 17.07 248 171692 447343 90009164
Type 2 diabetes mellitus 295.33 17.07 24 171916 203220 90253287
Ill-defined disorder 295.27 17.07 13 171927 184878 90271629
Haemoglobin decreased 286.08 17.07 813 171127 161143 90295364
Discomfort 280.19 17.07 86 171854 274249 90182258
Glossodynia 277.00 17.07 132 171808 321647 90134860
Asthma 273.71 17.07 62 171878 242098 90214409
Mobility decreased 270.12 17.07 71 171869 250663 90205844
Dysgeusia 269.67 17.07 410 171530 52150 90404357
Toxicity to various agents 268.54 17.07 105 171835 287741 90168766
Wheezing 267.00 17.07 62 171878 238018 90218489
Carbohydrate antigen 15-3 increased 263.82 17.07 110 171830 1897 90454610
Blood test abnormal 262.57 17.07 257 171683 20695 90435812
Completed suicide 258.86 17.07 3 171937 145055 90311452
White blood cell count abnormal 258.49 17.07 167 171773 7337 90449170
Blood cholesterol increased 237.59 17.07 52 171888 207960 90248547
Hypertension 224.61 17.07 325 171615 457207 89999300
Sleep disorder due to general medical condition, insomnia type 223.88 17.07 4 171936 128690 90327817
Bursitis 221.57 17.07 6 171934 131648 90324859
Therapeutic product effect incomplete 218.37 17.07 50 171890 193846 90262661
Liver injury 217.81 17.07 32 171908 170535 90285972
Musculoskeletal stiffness 212.16 17.07 152 171788 296380 90160127
Urticaria 210.10 17.07 171 171769 312563 90143944
Hepatic enzyme increased 209.71 17.07 225 171715 360511 90095996
Myelosuppression 208.54 17.07 369 171571 53222 90403285
Onychoclasis 207.66 17.07 145 171795 7254 90449253
Confusional state 198.84 17.07 265 171675 385940 90070567
Joint range of motion decreased 194.32 17.07 17 171923 135626 90320881
Laboratory test abnormal 193.15 17.07 311 171629 41543 90414964
Injection site pain 187.38 17.07 49 171891 173650 90282857
Cough 186.89 17.07 1269 170671 367693 90088814
PIK3CA-activated mutation 185.67 17.07 74 171866 1130 90455377
Impaired healing 182.48 17.07 109 171831 234090 90222417
COVID-19 181.50 17.07 717 171223 168126 90288381
Psoriasis 181.24 17.07 31 171909 147723 90308784
Obesity 180.63 17.07 4 171936 105503 90351004
Lacrimation increased 170.86 17.07 233 171707 26829 90429678
Ageusia 170.11 17.07 180 171760 15896 90440611
Overdose 169.14 17.07 45 171895 157664 90298843
Back pain 169.07 17.07 1105 170835 316070 90140437
Metastases to lung 167.35 17.07 178 171762 15813 90440694
Osteoarthritis 165.73 17.07 82 171858 195648 90260859
Hypercholesterolaemia 164.74 17.07 6 171934 100886 90355621
Cancer pain 162.32 17.07 99 171841 3926 90452581
Treatment failure 162.09 17.07 203 171737 303725 90152782
Hypotension 159.70 17.07 231 171709 325166 90131341
Adverse event 159.60 17.07 18 171922 117400 90339107
Madarosis 158.62 17.07 94 171846 3535 90452972
Sinusitis 156.46 17.07 256 171684 342832 90113675
Therapy change 153.61 17.07 127 171813 8195 90448312
Oedema 152.16 17.07 96 171844 200199 90256308
White blood cell disorder 151.48 17.07 85 171855 2879 90453628
C-reactive protein increased 150.56 17.07 78 171862 181311 90275196
Blister 149.28 17.07 158 171782 254840 90201667
Prescribed overdose 149.09 17.07 9 171931 97616 90358891
Mean cell volume increased 147.02 17.07 101 171839 4920 90451587
Haematotoxicity 146.42 17.07 148 171792 12387 90444120
Grip strength decreased 146.16 17.07 7 171933 92569 90363938
Injection site erythema 144.81 17.07 11 171929 98491 90358016
Tachycardia 144.53 17.07 59 171881 157614 90298893
Lymphoedema 142 17.07 152 171788 13601 90442906
Red blood cell sedimentation rate increased 141.90 17.07 3 171937 82592 90373915
Neoplasm recurrence 141.36 17.07 84 171856 3175 90453332
Condition aggravated 140.97 17.07 616 171324 594929 89861578
Wound infection 138.06 17.07 19 171921 106383 90350124
Peripheral venous disease 136.98 17.07 5 171935 83916 90372591
Pleural effusion 136.35 17.07 495 171445 111496 90345011
Gastrointestinal disorder 133.17 17.07 175 171765 256512 90199995
Pancytopenia 131.04 17.07 513 171427 119750 90336757
Product quality issue 128.53 17.07 5 171935 79320 90377187
Inflammation 128.37 17.07 91 171849 178501 90278006
Injection site reaction 128.00 17.07 13 171927 92067 90364440
Suicide attempt 121.33 17.07 5 171935 75394 90381113
Carbohydrate antigen 27.29 increased 120.80 17.07 31 171909 92 90456415
Prescribed underdose 120.64 17.07 5 171935 75014 90381493
Delirium 119.29 17.07 26 171914 104333 90352174
Medication error 117.54 17.07 12 171928 84640 90371867
Illness 116.97 17.07 382 171558 81587 90374920
Adverse drug reaction 114.78 17.07 39 171901 116662 90339845
Acute kidney injury 113.47 17.07 277 171663 320110 90136397
Breast pain 112.63 17.07 118 171822 10300 90446207
Autoimmune disorder 111.60 17.07 9 171931 76735 90379772
Flatulence 111.33 17.07 244 171696 41123 90415384
Road traffic accident 109.32 17.07 34 171906 107592 90348915
Immune system disorder 106.39 17.07 122 171818 11783 90444724
Oral mucosal blistering 106.11 17.07 95 171845 6829 90449678
Gait inability 104.76 17.07 75 171865 146381 90310126
Metastases to spine 101.89 17.07 72 171868 3671 90452836
Therapy non-responder 97.78 17.07 70 171870 136634 90319873
Weight increased 95.92 17.07 437 171503 417490 90039017
Foot deformity 92.61 17.07 5 171935 59646 90396861
Nasal dryness 92.36 17.07 80 171860 5503 90451004
Anaphylactic reaction 90.06 17.07 27 171913 87497 90369010
Epilepsy 88.99 17.07 23 171917 82183 90374324
Cardiac arrest 88.73 17.07 44 171896 104891 90351616
Coma 87.39 17.07 16 171924 72616 90383891
Adjustment disorder with depressed mood 87.35 17.07 5 171935 56748 90399759
Pulmonary fibrosis 86.58 17.07 48 171892 107455 90349052
Lower limb fracture 86.08 17.07 27 171913 84986 90371521
Bradycardia 86.03 17.07 26 171914 83821 90372686
Hepatic lesion 85.29 17.07 77 171863 5596 90450911
Knee arthroplasty 84.98 17.07 26 171914 83156 90373351
Body surface area increased 84.86 17.07 20 171920 36 90456471
Therapeutic response decreased 84.80 17.07 32 171908 89697 90366810
Gingival pain 84.72 17.07 98 171842 9554 90446953
Ascites 83.54 17.07 239 171701 47501 90409006
Hair texture abnormal 83.34 17.07 70 171870 4617 90451890
Musculoskeletal chest pain 82.83 17.07 156 171784 23594 90432913
Multiple sclerosis relapse 82.42 17.07 4 171936 52301 90404206
Injection site pruritus 82.08 17.07 5 171935 53829 90402678
Pneumonitis 82.08 17.07 226 171714 43944 90412563
Mean cell haemoglobin increased 81.42 17.07 64 171876 3841 90452666
Feeling cold 79.65 17.07 167 171773 27298 90429209
Thrombosis 79.38 17.07 312 171628 72939 90383568
Hip arthroplasty 79.34 17.07 23 171917 76185 90380322
General physical health deterioration 79.27 17.07 375 171565 354740 90101767
Tumour marker abnormal 78.57 17.07 29 171911 355 90456152
Depressed level of consciousness 77.58 17.07 21 171919 72763 90383744
Suicidal ideation 77.43 17.07 22 171918 73833 90382674
Pseudocirrhosis 76.84 17.07 37 171903 907 90455600
Drug interaction 76.06 17.07 269 171671 276184 90180323
Taste disorder 75.70 17.07 273 171667 61273 90395234
Bone cancer 75.13 17.07 44 171896 1618 90454889
Incorrect dose administered 74.84 17.07 28 171912 78902 90377605
Lip dry 74.44 17.07 50 171890 100905 90355602
Oropharyngeal pain 73.70 17.07 421 171519 114766 90341741
Cardio-respiratory arrest 73.66 17.07 15 171925 63125 90393382
Lupus-like syndrome 73.10 17.07 5 171935 48841 90407666
Mucosal inflammation 72.92 17.07 258 171682 57367 90399140
Exostosis 72.56 17.07 8 171932 53126 90403381
Metabolic acidosis 72.08 17.07 10 171930 55666 90400841
Sedation 71.88 17.07 5 171935 48166 90408341
Fall 71.49 17.07 578 171362 481232 89975275
Metastases to pleura 69.20 17.07 45 171895 1999 90454508
Hypoacusis 69.04 17.07 159 171781 27691 90428816
Decreased immune responsiveness 68.83 17.07 84 171856 8664 90447843
Chest pain 68.74 17.07 342 171598 319303 90137204
Dizziness 67.56 17.07 1527 170413 587757 89868750
Metastases to skin 67.31 17.07 45 171895 2095 90454412
Inappropriate schedule of product administration 67.22 17.07 113 171827 149820 90306687
Migraine 66.26 17.07 166 171774 190226 90266281
Injection site swelling 66.20 17.07 16 171924 59823 90396684
Carcinoembryonic antigen increased 65.82 17.07 46 171894 2304 90454203
Metastases to lymph nodes 65.40 17.07 95 171845 11594 90444913
Glomerular filtration rate decreased 65.09 17.07 116 171824 16816 90439691
Spinal pain 64.48 17.07 111 171829 15656 90440851
Seizure 63.94 17.07 120 171820 152509 90303998
Product use in unapproved indication 63.88 17.07 375 171565 335861 90120646
Body surface area decreased 63.30 17.07 15 171925 28 90456479
Erythema 63.09 17.07 223 171717 229023 90227484
Breast cancer recurrent 62.49 17.07 64 171876 5439 90451068
Dysphagia 62.03 17.07 395 171545 111883 90344624
Oedema peripheral 61.94 17.07 265 171675 257650 90198857
Infection 61.02 17.07 419 171521 361675 90094832
Drug ineffective for unapproved indication 60.95 17.07 25 171915 66619 90389888
Pneumonia 60.72 17.07 849 171091 637210 89819297
Sciatica 60.20 17.07 62 171878 101320 90355187
Joint dislocation 60.16 17.07 7 171933 44575 90411932
Angioedema 59.88 17.07 24 171916 64852 90391655
Lactic acidosis 58.84 17.07 12 171928 50451 90406056
Syncope 58.53 17.07 101 171839 132562 90323945
Malignant pleural effusion 58.42 17.07 47 171893 2917 90453590
Hypoglycaemia 57.98 17.07 30 171910 69818 90386689
Hypokalaemia 56.78 17.07 101 171839 131015 90325492
Product dispensing error 56.34 17.07 91 171849 12182 90444325
Plasma cell myeloma 56.13 17.07 6 171934 40822 90415685
Multiple organ dysfunction syndrome 55.77 17.07 30 171910 68306 90388201
Pulmonary thrombosis 55.46 17.07 80 171860 9702 90446805
Product packaging difficult to open 54.21 17.07 17 171923 121 90456386
Injection site bruising 54.06 17.07 16 171924 52291 90404216
Septic shock 54.01 17.07 48 171892 84112 90372395
Incorrect route of product administration 53.22 17.07 15 171925 50611 90405896
Appetite disorder 52.23 17.07 75 171865 9058 90447449
Encephalopathy 52.21 17.07 12 171928 46432 90410075
Blood pressure increased 52.18 17.07 195 171745 197022 90259485
Hyponatraemia 51.64 17.07 110 171830 133428 90323079
Abdominal pain 50.61 17.07 493 171447 395228 90061279
Respiratory failure 50.58 17.07 92 171848 118326 90338181
Lung disorder 50.36 17.07 133 171807 149750 90306757
Pulmonary embolism 50.28 17.07 422 171518 130398 90326109
Oxygen saturation decreased 50.05 17.07 79 171861 107404 90349103
Pancreatitis 49.60 17.07 36 171904 69790 90386717
Drug tolerance decreased 48.93 17.07 3 171937 32127 90424380
Back injury 48.66 17.07 14 171926 46608 90409899
Underdose 48.21 17.07 21 171919 53996 90402511
Respiratory arrest 48.17 17.07 4 171936 33307 90423200
Altered state of consciousness 47.85 17.07 3 171937 31529 90424978
Metastases to kidney 47.72 17.07 18 171922 235 90456272
Skin exfoliation 47.29 17.07 254 171686 67659 90388848
Flushing 47.22 17.07 59 171881 88432 90368075
Nail growth abnormal 47.20 17.07 23 171917 579 90455928
Rhinorrhoea 47.12 17.07 308 171632 88008 90368499
Radiation injury 47.09 17.07 24 171916 667 90455840
Renal impairment 47.05 17.07 352 171588 105069 90351438
Colitis ulcerative 46.96 17.07 28 171912 60238 90396269
Walking aid user 46.86 17.07 6 171934 35500 90421007
Metastases to peritoneum 46.60 17.07 48 171892 4107 90452400
Vomiting 46.55 17.07 1882 170058 786411 89670096
Metastases to retroperitoneum 45.72 17.07 16 171924 166 90456341
Blood pressure systolic increased 45.62 17.07 27 171913 58318 90398189
Weight decreased 44.88 17.07 989 170951 378921 90077586
No adverse event 44.56 17.07 38 171902 67944 90388563
Dysarthria 44.34 17.07 24 171916 54458 90402049
Leukocytosis 44.05 17.07 4 171936 30986 90425521
Loss of consciousness 43.73 17.07 129 171811 140109 90316398
Oophorectomy bilateral 43.67 17.07 14 171926 108 90456399
Muscular weakness 43.33 17.07 223 171717 206443 90250064
Neutrophil count abnormal 43.28 17.07 46 171894 4082 90452425
Hyperkalaemia 42.97 17.07 36 171904 64928 90391579
Orthostatic hypotension 42.85 17.07 13 171927 41814 90414693
Hypersomnia 42.84 17.07 113 171827 21418 90435089
Haematocrit decreased 42.77 17.07 175 171765 41657 90414850
Loss of personal independence in daily activities 42.58 17.07 125 171815 135980 90320527
Palpitations 42.47 17.07 126 171814 136602 90319905
Gastrointestinal haemorrhage 42.33 17.07 66 171874 90182 90366325
Myalgia 42.19 17.07 513 171427 174612 90281895
Adrenal insufficiency 42.16 17.07 4 171936 29917 90426590
Injection site haemorrhage 42.08 17.07 3 171937 28315 90428192
Psychotic disorder 41.90 17.07 5 171935 31225 90425282
Adverse reaction 41.80 17.07 4 171936 29708 90426799
Chills 41.67 17.07 408 171532 131573 90324934
Pneumonia aspiration 41.45 17.07 13 171927 40927 90415580
Trichorrhexis 41.40 17.07 29 171911 1458 90455049
Metastases to central nervous system 41.13 17.07 98 171842 17444 90439063
Drug dependence 41.12 17.07 4 171936 29323 90427184
Ear infection 41.05 17.07 43 171897 69732 90386775
Onychomadesis 40.87 17.07 18 171922 45980 90410527
Unresponsive to stimuli 40.62 17.07 11 171929 38110 90418397
Pulmonary hypertension 40.45 17.07 15 171925 42508 90413999
Emotional distress 40.17 17.07 10 171930 36652 90419855
Hallucination 39.54 17.07 40 171900 65919 90390588
Osteoporosis 39.46 17.07 77 171863 96454 90360053
Unevaluable event 39.32 17.07 28 171912 54820 90401687
Eating disorder 39.28 17.07 130 171810 27943 90428564
Dry eye 39.21 17.07 215 171725 57716 90398791
Faeces soft 39.08 17.07 59 171881 7452 90449055
Cytomegalovirus infection 39.01 17.07 3 171937 26599 90429908
Aphthous ulcer 38.85 17.07 95 171845 17192 90439315
Eastern Cooperative Oncology Group performance status worsened 38.76 17.07 31 171909 1908 90454599
Hair growth abnormal 38.60 17.07 41 171899 3635 90452872
International normalised ratio increased 38.28 17.07 21 171919 47295 90409212
Onychomycosis 37.60 17.07 12 171928 37364 90419143
Red blood cell count abnormal 37.51 17.07 26 171914 1285 90455222
Feeling abnormal 37.33 17.07 483 171457 166752 90289755
Blood pressure fluctuation 37.25 17.07 27 171913 52386 90404121
Sleep disorder 36.97 17.07 222 171718 197808 90258699
Off label use 36.89 17.07 1713 170227 1100539 89355968
Hypoxia 36.85 17.07 50 171890 72349 90384158
Granulocyte count decreased 36.31 17.07 33 171907 2419 90454088
Arthralgia 36.15 17.07 1814 170126 776708 89679799
Metastasis 35.98 17.07 51 171889 6086 90450421
Haematuria 35.54 17.07 11 171929 34926 90421581
Agitation 35.52 17.07 45 171895 67053 90389454
Generalised tonic-clonic seizure 35.48 17.07 11 171929 34892 90421615
Heart rate increased 35.09 17.07 104 171836 112798 90343709
Urine odour abnormal 35.02 17.07 55 171885 7189 90449318
Hepatitis 34.86 17.07 50 171890 70689 90385818
Hair disorder 34.43 17.07 24 171916 1197 90455310
Adnexa uteri mass 34.31 17.07 19 171921 627 90455880
Sleep apnoea syndrome 34.13 17.07 9 171931 31738 90424769
Musculoskeletal pain 34.10 17.07 188 171752 171063 90285444
Poor quality product administered 34.02 17.07 40 171900 3968 90452539
Toothache 33.88 17.07 106 171834 22124 90434383
Rectal haemorrhage 33.82 17.07 66 171874 82678 90373829
Body temperature increased 33.15 17.07 22 171918 44688 90411819
Arthritis 33.14 17.07 184 171756 167131 90289376
Basal cell carcinoma 33.10 17.07 11 171929 33378 90423129
Acute cutaneous lupus erythematosus 32.97 17.07 15 171925 322 90456185
Feeding disorder 32.92 17.07 90 171850 17422 90439085
Monocyte count decreased 32.86 17.07 32 171908 2559 90453948
Sinus tachycardia 32.79 17.07 7 171933 28506 90428001
Breast cancer 32.75 17.07 194 171746 53567 90402940
Tongue disorder 32.62 17.07 67 171873 10793 90445714
Heart rate decreased 32.58 17.07 32 171908 53473 90403034
Mastectomy 32.56 17.07 29 171911 2070 90454437
Nasal discomfort 32.37 17.07 46 171894 5502 90451005
Blood creatine phosphokinase increased 32.37 17.07 12 171928 34011 90422496
Bone marrow infiltration 32.15 17.07 20 171920 822 90455685
Blood pressure diastolic decreased 32.07 17.07 6 171934 26820 90429687
Macular degeneration 31.97 17.07 16 171924 37954 90418553
Metastases to adrenals 31.81 17.07 21 171919 957 90455550
Withdrawal syndrome 31.77 17.07 3 171937 22521 90433986
Toxic epidermal necrolysis 31.75 17.07 11 171929 32517 90423990
Oestrogen receptor assay positive 31.72 17.07 17 171923 525 90455982
Palmar-plantar erythrodysaesthesia syndrome 31.69 17.07 121 171819 27902 90428605
Gingival bleeding 31.49 17.07 80 171860 14823 90441684
Chronic sinusitis 31.47 17.07 4 171936 23798 90432709
Bone lesion 31.30 17.07 49 171891 6388 90450119
Therapeutic response unexpected 31.22 17.07 102 171838 21778 90434729
Increased appetite 31.20 17.07 69 171871 11696 90444811
Tongue discomfort 31.11 17.07 32 171908 2733 90453774
Metastases to bladder 31.03 17.07 13 171927 227 90456280
Foreign body in throat 30.83 17.07 16 171924 462 90456045
Angina pectoris 30.79 17.07 18 171922 39142 90417365
Ovarian disorder 30.78 17.07 20 171920 887 90455620
Parosmia 30.54 17.07 51 171889 7018 90449489
Obstructive airways disorder 30.47 17.07 6 171934 25863 90430644
Drug-induced liver injury 30.44 17.07 80 171860 90238 90366269
Coronary artery disease 30.12 17.07 13 171927 33610 90422897
Product label confusion 29.82 17.07 4 171936 22846 90433661
Injection site rash 29.79 17.07 5 171935 24168 90432339
Drug level increased 29.60 17.07 8 171932 27754 90428753
Vasculitis 29.55 17.07 4 171936 22689 90433818
Emotional disorder 29.12 17.07 78 171862 14919 90441588
Eructation 29.06 17.07 64 171876 10818 90445689
Ventricular tachycardia 28.55 17.07 6 171934 24702 90431805
Hypomagnesaemia 28.49 17.07 16 171924 35572 90420935
Dyskinesia 28.43 17.07 17 171923 36517 90419990
Heavy menstrual bleeding 28.26 17.07 3 171937 20527 90435980
Acute myocardial infarction 27.48 17.07 16 171924 34874 90421633
Staphylococcal infection 27.22 17.07 31 171909 48408 90408099
Tachypnoea 27.18 17.07 4 171936 21305 90435202
Tumour pain 27.17 17.07 25 171915 1862 90454645
Anaphylactic shock 27.11 17.07 13 171927 31604 90424903
Mitral valve incompetence 27.01 17.07 5 171935 22519 90433988
Renal surgery 26.96 17.07 11 171929 179 90456328
Nail discolouration 26.93 17.07 32 171908 3210 90453297
Mental status changes 26.89 17.07 27 171913 44652 90411855
Dental discomfort 26.84 17.07 15 171925 504 90456003
Blood calcium decreased 26.80 17.07 121 171819 30061 90426446
Device malfunction 26.61 17.07 4 171936 20973 90435534
Dermatitis atopic 26.51 17.07 6 171934 23466 90433041
Respiratory distress 26.48 17.07 21 171919 38925 90417582
Red cell distribution width increased 26.28 17.07 66 171874 12141 90444366
Multiple sclerosis 26.18 17.07 10 171930 27830 90428677
Artificial menopause 25.67 17.07 7 171933 28 90456479
Dyspnoea exertional 25.57 17.07 229 171711 72059 90384448
Ulcer haemorrhage 25.52 17.07 9 171931 26312 90430195
Rash maculo-papular 25.48 17.07 24 171916 40909 90415598
Pyrexia 25.44 17.07 1010 170930 659475 89797032
Respiratory disorder 25.38 17.07 53 171887 64763 90391744
Liver disorder 25.32 17.07 131 171809 121138 90335369
Stevens-Johnson syndrome 25.31 17.07 12 171928 29364 90427143
Prehypertension 24.92 17.07 7 171933 32 90456475
Peripheral swelling 24.91 17.07 595 171345 412511 90043996
Product prescribing issue 24.88 17.07 50 171890 7929 90448578
Triple negative breast cancer 24.57 17.07 13 171927 391 90456116
Joint effusion 24.46 17.07 4 171936 19706 90436801
Shock 24.42 17.07 12 171928 28766 90427741
Basophil count increased 24.29 17.07 19 171921 1132 90455375
Tooth disorder 24.22 17.07 120 171820 30970 90425537
Urinary tract infection 24.22 17.07 755 171185 304877 90151630
Food allergy 24.21 17.07 9 171931 25469 90431038
Pain of skin 23.88 17.07 76 171864 16006 90440501
Swelling face 23.82 17.07 77 171863 81275 90375232
Incorrect product administration duration 23.80 17.07 4 171936 19318 90437189
Pleural neoplasm 23.78 17.07 13 171927 418 90456089
Wrong technique in product usage process 23.66 17.07 64 171876 71507 90385000
Metastases to the mediastinum 23.56 17.07 15 171925 642 90455865
Melaena 23.36 17.07 19 171921 34778 90421729
Hypogeusia 23.24 17.07 21 171919 1528 90454979
Treatment noncompliance 23.16 17.07 39 171901 51688 90404819
Tremor 23.00 17.07 183 171757 152990 90303517
Drug eruption 22.95 17.07 20 171920 35387 90421120
Tongue blistering 22.93 17.07 23 171917 1907 90454600
Lip pain 22.80 17.07 24 171916 2106 90454401
Metastases to pelvis 22.80 17.07 14 171926 562 90455945
Metastases to eye 22.67 17.07 10 171930 199 90456308
Proteinuria 22.52 17.07 8 171932 23283 90433224
Oral disorder 22.35 17.07 56 171884 10289 90446218
Blood creatinine increased 22.27 17.07 292 171648 101094 90355413
Neoplasm 22.25 17.07 51 171889 8852 90447655
Hepatic failure 22.07 17.07 140 171800 39588 90416919
Radiation fibrosis - lung 21.95 17.07 7 171933 53 90456454
Haematoma 21.93 17.07 25 171915 39023 90417484
Complication associated with device 21.91 17.07 5 171935 19444 90437063
Hypervolaemia 21.85 17.07 18 171922 32739 90423768
Nasal disorder 21.77 17.07 29 171911 3263 90453244
Product use complaint 21.67 17.07 30 171910 3503 90453004
Chapped lips 21.66 17.07 27 171913 2846 90453661
Infusion site coldness 21.55 17.07 10 171930 225 90456282
Drug tolerance 21.43 17.07 4 171936 17912 90438595
Acute respiratory distress syndrome 21.42 17.07 14 171926 28672 90427835
Pallor 21.31 17.07 20 171920 34145 90422362
Bone cancer metastatic 21.19 17.07 10 171930 234 90456273
Peritoneal fluid analysis abnormal 21.09 17.07 6 171934 29 90456478
Cardiogenic shock 21.07 17.07 10 171930 24458 90432049
Joint neoplasm 20.89 17.07 7 171933 63 90456444
Metastases to chest wall 20.84 17.07 14 171926 657 90455850
Vulvovaginal dryness 20.84 17.07 29 171911 3402 90453105
Noninfective gingivitis 20.84 17.07 23 171917 2130 90454377
Blood glucose increased 20.79 17.07 274 171666 94972 90361535
Metastases to gastrointestinal tract 20.77 17.07 8 171932 111 90456396
Dehydration 20.69 17.07 499 171441 193948 90262559
Muscle twitching 20.68 17.07 10 171930 24192 90432315
Pulmonary arterial hypertension 20.64 17.07 12 171928 26175 90430332
Gait disturbance 20.51 17.07 359 171581 260137 90196370
Hepatotoxicity 20.41 17.07 153 171787 45689 90410818
Macrocytosis 20.33 17.07 26 171914 2812 90453695
Basophil percentage increased 20.26 17.07 8 171932 119 90456388
Abnormal behaviour 19.87 17.07 9 171931 22619 90433888
Radiation fibrosis 19.87 17.07 6 171934 37 90456470
Anaemia macrocytic 19.77 17.07 33 171907 4539 90451968
Poikilocytosis 19.75 17.07 9 171931 194 90456313
Radiation oesophagitis 19.74 17.07 12 171928 473 90456034
Fingerprint loss 19.60 17.07 6 171934 39 90456468
Metastases to spinal cord 19.52 17.07 10 171930 281 90456226
Eczema 19.24 17.07 45 171895 52825 90403682
Hunger 19.14 17.07 40 171900 6523 90449984
Hormone receptor positive HER2 negative breast cancer 19.11 17.07 10 171930 294 90456213
Hormone receptor positive breast cancer 18.92 17.07 14 171926 767 90455740
Cardiac failure congestive 18.75 17.07 110 171830 98584 90357923
Hypothyroidism 18.72 17.07 46 171894 53081 90403426
Pulmonary oedema 18.66 17.07 190 171750 61890 90394617
Aggression 18.61 17.07 14 171926 26654 90429853
Breast haemorrhage 18.49 17.07 9 171931 226 90456281
Interstitial lung disease 18.46 17.07 224 171716 76181 90380326
Hepatic cirrhosis 18.42 17.07 60 171880 63193 90393314
Thyroid calcification 18.42 17.07 6 171934 49 90456458
Platelet count abnormal 18.36 17.07 31 171909 4304 90452203
Blood potassium decreased 18.35 17.07 154 171786 47573 90408934
Cyanosis 18.28 17.07 7 171933 19448 90437059
Hallucination, auditory 18.21 17.07 4 171936 15971 90440536
Hyperaesthesia teeth 18.13 17.07 22 171918 2255 90454252
Tubulointerstitial nephritis 18.08 17.07 13 171927 25330 90431177
Temperature regulation disorder 18.00 17.07 3 171937 14576 90441931
Insomnia 17.97 17.07 789 171151 332685 90123822
Motor dysfunction 17.93 17.07 7 171933 19223 90437284
Retching 17.91 17.07 78 171862 19081 90437426
Laryngitis 17.84 17.07 44 171896 50709 90405798
Soft tissue neoplasm 17.80 17.07 7 171933 103 90456404
Product substitution issue 17.73 17.07 6 171934 18002 90438505
Skin sensitisation 17.72 17.07 15 171925 1000 90455507
Hallucination, visual 17.61 17.07 11 171929 23081 90433426
Upper respiratory tract infection 17.60 17.07 157 171783 128161 90328346
Respiratory depression 17.55 17.07 4 171936 15571 90440936
Gamma-glutamyltransferase decreased 17.50 17.07 10 171930 351 90456156
Metastases to abdominal cavity 17.22 17.07 12 171928 598 90455909
Immunodeficiency 17.22 17.07 35 171905 43199 90413308
Parkinsonism 17.13 17.07 3 171937 14062 90442445
Contusion 17.08 17.07 355 171585 250861 90205646

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
Neoplasm progression 558.35 31.71 170 3406 28830 42588929
Product use issue 551.91 31.71 215 3361 76536 42541223
Fatigue 163.11 31.71 190 3386 435451 42182308
Off label use 128.41 31.71 206 3370 638129 41979630
White blood cell count decreased 122.54 31.71 89 3487 110307 42507452
Product use in unapproved indication 99.32 31.71 98 3478 184358 42433401
Neutropenia 89.33 31.71 96 3480 199335 42418424
Hot flush 66.54 31.71 34 3542 22317 42595442
Death 57.14 31.71 123 3453 471062 42146697
Hydrocephalus 53.95 31.71 20 3556 6058 42611701
Xerosis 38.78 31.71 10 3566 906 42616853
Alopecia 37.88 31.71 26 3550 29250 42588509
Disease progression 34.84 31.71 51 3525 143605 42474154

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
Neoplasm progression 15747.29 18.14 5189 157378 59406 110367326
White blood cell count decreased 11867.78 18.14 6054 156513 223336 110203396
Fatigue 7736.78 18.14 9142 153425 1206816 109219916
Neutropenia 4469.13 18.14 3975 158592 370645 110056087
Alopecia 3456.52 18.14 3408 159159 361345 110065387
Nausea 2146.23 18.14 5223 157344 1230467 109196265
Full blood count decreased 2115.89 18.14 1004 161563 31095 110395637
Full blood count abnormal 1930.37 18.14 1136 161431 54916 110371816
Hot flush 1855.59 18.14 1175 161392 64861 110361871
Neutrophil count decreased 1524.29 18.14 1328 161239 119613 110307119
Red blood cell count decreased 1326.88 18.14 954 161613 64969 110361763
Stomatitis 1121.72 18.14 1664 160903 268578 110158154
Tumour marker increased 1075.57 18.14 368 162199 4692 110422040
Drug ineffective 952.91 18.14 529 162038 1520011 108906721
Product dose omission issue 878.76 18.14 1642 160925 320140 110106592
Decreased appetite 869.15 18.14 2059 160508 473787 109952945
Constipation 782.51 18.14 1664 160903 356122 110070610
Diarrhoea 753.43 18.14 3485 159082 1136020 109290712
Bone pain 745.94 18.14 678 161889 64455 110362277
Death 660.17 18.14 2389 160178 696480 109730252
Oral pain 650.08 18.14 496 162071 36948 110389784
Metastases to bone 642.36 18.14 459 162108 30913 110395819
Disease progression 614.78 18.14 1204 161363 242830 110183902
Dry skin 609.29 18.14 771 161796 106882 110319850
Platelet count decreased 606.21 18.14 1158 161409 229285 110197447
Product dose omission in error 530.25 18.14 365 162202 23147 110403585
Infusion related reaction 519.26 18.14 8 162559 381154 110045578
Leukopenia 515.62 18.14 844 161723 147947 110278785
Epistaxis 506.14 18.14 779 161788 129593 110297139
Second primary malignancy 503.28 18.14 320 162247 17748 110408984
Malignant neoplasm progression 480.95 18.14 895 161672 173672 110253060
Toxicity to various agents 432.16 18.14 90 162477 480465 109946267
Asthenia 413.74 18.14 2053 160514 686946 109739786
Rheumatoid arthritis 378.71 18.14 14 162553 299599 110127133
Maternal exposure during pregnancy 357.62 18.14 3 162564 254880 110171852
Acute kidney injury 344.26 18.14 259 162308 635171 109791561
Contraindicated product administered 343.30 18.14 4 162563 248263 110178469
Bone marrow failure 342.61 18.14 424 162143 57424 110369308
Drug hypersensitivity 311.27 18.14 139 162428 453951 109972781
Metastases to liver 308.15 18.14 317 162250 35069 110391663
Neuropathy peripheral 306.05 18.14 757 161810 178520 110248212
Hand deformity 304.50 18.14 3 162564 218503 110208229
Therapeutic product effect decreased 300.09 18.14 14 162553 244302 110182430
Pericarditis 296.58 18.14 5 162562 219109 110207623
White blood cell count abnormal 294.12 18.14 161 162406 6748 110419984
Systemic lupus erythematosus 292.80 18.14 21 162546 254317 110172415
Intentional product use issue 272.79 18.14 25 162542 247881 110178851
Therapy cessation 272.42 18.14 333 162234 44524 110382208
Psoriatic arthropathy 268.37 18.14 4 162563 196757 110229975
Carbohydrate antigen 15-3 increased 266.94 18.14 97 162470 1490 110425242
Hypotension 261.82 18.14 231 162336 523618 109903114
Treatment failure 261.59 18.14 46 162521 277188 110149544
Dysgeusia 254.52 18.14 406 162161 69579 110357153
Blood test abnormal 245.38 18.14 254 162313 28300 110398432
Laboratory test abnormal 241.80 18.14 311 162256 43768 110382964
Joint swelling 231.39 18.14 187 162380 442658 109984074
Osteonecrosis of jaw 229.93 18.14 317 162250 47700 110379032
Onychoclasis 228.92 18.14 139 162428 7098 110419634
Arthropathy 227.18 18.14 70 162497 287452 110139280
Lower respiratory tract infection 225.75 18.14 42 162525 243064 110183668
Overdose 220.10 18.14 39 162528 233755 110192977
Drug interaction 214.15 18.14 252 162315 499931 109926801
Breast cancer metastatic 207.07 18.14 154 162413 11027 110415705
Asthma 204.93 18.14 57 162510 250234 110176498
Wheezing 201.87 18.14 62 162505 255168 110171564
Wound 200.31 18.14 49 162518 234388 110192344
Injury 197.36 18.14 17 162550 177248 110249484
Lacrimation increased 194.82 18.14 234 162333 30716 110396016
Back pain 192.63 18.14 1063 161504 369933 110056799
Haemoglobin decreased 192.60 18.14 800 161767 247927 110178805
Cytopenia 191.71 18.14 229 162338 29887 110396845
Swelling 189.95 18.14 143 162424 350898 110075834
Ill-defined disorder 189.35 18.14 10 162557 156843 110269889
Drug intolerance 186.95 18.14 193 162374 406319 110020413
Type 2 diabetes mellitus 186.83 18.14 21 162546 177211 110249521
Therapeutic product effect incomplete 185.03 18.14 50 162517 223755 110202977
Cough 183.45 18.14 1234 161333 460407 109966325
Irritable bowel syndrome 182.13 18.14 16 162551 164199 110262533
Confusional state 178.12 18.14 258 162309 468422 109958310
Fibromyalgia 175.82 18.14 22 162545 170887 110255845
Illness 174.23 18.14 378 162189 81793 110344939
Hypersensitivity 172.36 18.14 204 162363 403794 110022938
Cardiac arrest 170.29 18.14 40 162527 196713 110230019
Hypertension 170.18 18.14 306 162261 509778 109916954
Bursitis 167.87 18.14 5 162562 129913 110296819
Lymphoedema 166.10 18.14 153 162414 14776 110411956
Mobility decreased 165.19 18.14 71 162496 237351 110189381
Tachycardia 163.81 18.14 64 162503 226581 110200151
Anaemia 162.86 18.14 1366 161201 545720 109881012
Madarosis 162.23 18.14 86 162481 3377 110423355
Ageusia 155.01 18.14 167 162400 19478 110407254
Thrombocytopenia 147.85 18.14 948 161619 347937 110078795
Obesity 144.18 18.14 5 162562 113346 110313386
White blood cell disorder 142.72 18.14 82 162485 3777 110422955
C-reactive protein increased 142.56 18.14 71 162496 217848 110208884
Urticaria 141.40 18.14 156 162411 318701 110108031
Bradycardia 139.86 18.14 29 162538 155488 110271244
Injection site pain 139.27 18.14 44 162523 177878 110248854
Blood cholesterol increased 138.87 18.14 49 162518 184736 110241996
Liver injury 137.45 18.14 27 162540 150386 110276346
Multiple organ dysfunction syndrome 137.03 18.14 28 162539 151682 110275050
Sleep disorder due to general medical condition, insomnia type 136.73 18.14 4 162563 105639 110321093
Delirium 132.69 18.14 20 162547 135005 110291727
Condition aggravated 131.71 18.14 594 161973 734242 109692490
Breast pain 130.16 18.14 112 162455 9888 110416844
Arthralgia 129.52 18.14 1730 160837 777902 109648830
Suicide attempt 126.66 18.14 6 162561 103388 110323344
Therapy change 126.15 18.14 110 162457 9887 110416845
Discomfort 125.99 18.14 80 162487 214627 110212105
COVID-19 124.28 18.14 698 161869 244362 110182370
Myelosuppression 124.16 18.14 362 162205 93978 110332754
Cancer pain 122.56 18.14 92 162475 6680 110420052
Joint range of motion decreased 122.15 18.14 17 162550 121815 110304917
Cardio-respiratory arrest 121.38 18.14 14 162553 115822 110310910
Carbohydrate antigen 27.29 increased 120.12 18.14 29 162538 87 110426645
Psoriasis 120.06 18.14 29 162538 139964 110286768
Respiratory failure 119.95 18.14 85 162482 215247 110211485
Musculoskeletal stiffness 119.60 18.14 141 162426 279681 110147051
Coma 116.88 18.14 17 162550 117852 110308880
Septic shock 116.28 18.14 43 162524 157485 110269247
Flatulence 112.94 18.14 242 162325 51907 110374825
Pneumonia 112.91 18.14 790 161777 875924 109550808
Hyperkalaemia 112.85 18.14 30 162537 135766 110290966
Neoplasm recurrence 112.73 18.14 79 162488 5153 110421579
Metabolic acidosis 112.57 18.14 9 162558 99735 110326997
Medication error 112.26 18.14 12 162555 105354 110321378
Adverse event 111.91 18.14 14 162553 108795 110317937
Depressed level of consciousness 111.78 18.14 16 162551 112262 110314470
Oral mucosal blistering 111.77 18.14 93 162474 7841 110418891
Metastases to lung 110.00 18.14 152 162415 22911 110403821
Oedema 107.89 18.14 90 162477 209886 110216846
Mean cell volume increased 107.82 18.14 93 162474 8237 110418495
Gastrointestinal haemorrhage 106.64 18.14 55 162512 165463 110261269
Taste disorder 105.08 18.14 270 162297 65117 110361615
Hair texture abnormal 105.07 18.14 68 162499 3886 110422846
Peripheral venous disease 102.66 18.14 5 162562 84112 110342620
Injection site erythema 102.21 18.14 10 162557 94166 110332566
Nasal dryness 102.11 18.14 77 162490 5629 110421103
Anaphylactic reaction 101.36 18.14 22 162545 114278 110312454
Osteoarthritis 100.51 18.14 73 162494 182550 110244182
Therapy non-responder 100.26 18.14 53 162514 157254 110269478
Hepatic enzyme increased 98.62 18.14 202 162365 320690 110106042
Hyponatraemia 98.10 18.14 105 162462 217548 110209184
Lactic acidosis 97.78 18.14 11 162556 92800 110333932
Red blood cell sedimentation rate increased 97.70 18.14 4 162563 78298 110348434
Hypercholesterolaemia 97.66 18.14 10 162557 90827 110335905
Product use issue 97.24 18.14 787 161780 310908 110115824
Product quality issue 96.28 18.14 4 162563 77295 110349437
Prescribed overdose 95.84 18.14 9 162558 87572 110339160
Seizure 94.99 18.14 111 162456 221074 110205658
Immune system disorder 94.83 18.14 108 162459 13393 110413339
Haematotoxicity 94.69 18.14 135 162432 20947 110405785
Drug ineffective for unapproved indication 92.82 18.14 19 162548 102819 110323913
Oropharyngeal pain 92.28 18.14 419 162148 134857 110291875
Grip strength decreased 91.13 18.14 7 162560 80167 110346565
Syncope 90.95 18.14 98 162469 202438 110224294
Hypoglycaemia 90.33 18.14 29 162538 116075 110310657
Injection site reaction 90.30 18.14 12 162555 89058 110337674
General physical health deterioration 84.60 18.14 330 162237 424965 110001767
Tumour marker abnormal 84.45 18.14 27 162540 274 110426458
Inflammation 84.03 18.14 96 162471 193142 110233590
Epilepsy 83.52 18.14 22 162545 100187 110326545
Decreased immune responsiveness 83.51 18.14 86 162481 9520 110417212
Inappropriate schedule of product administration 83.42 18.14 106 162461 203531 110223201
Angioedema 83.30 18.14 21 162546 98479 110328253
Dizziness 82.90 18.14 1464 161103 696729 109730003
Impaired healing 82.04 18.14 101 162466 196616 110230116
Feeling cold 80.94 18.14 164 162403 33823 110392909
Incorrect dose administered 80.43 18.14 26 162541 103615 110323117
Febrile neutropenia 80.13 18.14 221 162346 316546 110110186
Encephalopathy 79.64 18.14 12 162555 81043 110345689
Sedation 79.44 18.14 6 162561 69677 110357055
Prescribed underdose 79.13 18.14 4 162563 65170 110361562
Haematuria 77.74 18.14 14 162553 82991 110343741
Pneumonia aspiration 77.62 18.14 13 162554 81220 110345512
Pseudocirrhosis 76.88 18.14 34 162533 889 110425843
Glossodynia 76.81 18.14 130 162437 221874 110204858
Sepsis 76.54 18.14 237 162330 327109 110099623
Suicidal ideation 75.72 18.14 22 162545 93915 110332817
Musculoskeletal chest pain 75.71 18.14 145 162422 28702 110398030
Fall 75.02 18.14 549 162018 602933 109823799
Acute myocardial infarction 74.54 18.14 16 162551 83761 110342971
Adverse drug reaction 74.29 18.14 31 162536 105528 110321204
PIK3CA-activated mutation 73.35 18.14 30 162537 643 110426089
Road traffic accident 73.27 18.14 33 162534 107365 110319367
Vomiting 72.92 18.14 1802 160765 908873 109517859
Oedema peripheral 72.63 18.14 244 162323 328416 110098316
International normalised ratio increased 72.41 18.14 19 162548 86753 110339979
Blood pressure systolic increased 71.53 18.14 17 162550 82974 110343758
Hypoxia 70.96 18.14 52 162515 129463 110297269
Autoimmune disorder 70.94 18.14 7 162560 65476 110361256
Hypokalaemia 70.62 18.14 99 162468 182349 110244383
Therapeutic response decreased 70.10 18.14 27 162540 96472 110330260
Respiratory arrest 69.46 18.14 4 162563 58295 110368437
Oxygen saturation decreased 69.32 18.14 77 162490 156905 110269827
Mean cell haemoglobin increased 69.25 18.14 61 162506 5556 110421176
Altered state of consciousness 68.52 18.14 4 162563 57622 110369110
Cytomegalovirus infection 67.20 18.14 3 162564 54441 110372291
Hypoacusis 66.86 18.14 155 162412 35036 110391696
Carcinoembryonic antigen increased 66.40 18.14 45 162522 2779 110423953
Blister 65.78 18.14 148 162419 227228 110199504
Coronary artery disease 65.21 18.14 13 162554 71677 110355055
Product packaging difficult to open 65.13 18.14 17 162550 76 110426656
Appetite disorder 65.01 18.14 76 162491 9693 110417039
Plasma cell myeloma 64.96 18.14 8 162559 62928 110363804
Hallucination 64.88 18.14 34 162533 101398 110325334
Body surface area increased 64.56 18.14 19 162548 142 110426590
Incorrect route of product administration 64.06 18.14 9 162558 64052 110362680
Blood pressure increased 64.04 18.14 182 162385 258191 110168541
Spinal pain 64.00 18.14 105 162462 18410 110408322
Gingival pain 63.77 18.14 96 162471 15640 110411092
Pleural effusion 63.34 18.14 463 162104 177246 110249486
Erythema 63.28 18.14 218 162349 291229 110135503
Dry eye 63.04 18.14 203 162364 55590 110371142
Blood creatine phosphokinase increased 62.92 18.14 15 162552 73062 110353670
Injection site pruritus 62.70 18.14 3 162564 51255 110375477
Gastrointestinal disorder 62.53 18.14 167 162400 241785 110184947
Agitation 62.44 18.14 45 162522 113006 110313726
Orthostatic hypotension 62.42 18.14 11 162556 66238 110360494
Feeling abnormal 61.67 18.14 466 162101 180245 110246487
Loss of consciousness 61.62 18.14 122 162445 196184 110230548
Multiple sclerosis relapse 61.26 18.14 3 162564 50237 110376495
Accidental exposure to product 60.93 18.14 3 162564 50005 110376727
Wound infection 60.73 18.14 33 162534 96432 110330300
Pancreatitis 60.35 18.14 31 162536 93502 110333230
Body surface area decreased 60.05 18.14 15 162552 54 110426678
Dysarthria 58.72 18.14 25 162542 84096 110342636
Product dispensing error 58.27 18.14 94 162473 16251 110410481
Memory impairment 58.01 18.14 491 162076 196453 110230279
Drug dependence 57.90 18.14 4 162563 50016 110376716
Leukocytosis 57.67 18.14 6 162561 53822 110372910
Trichorrhexis 57.49 18.14 28 162539 917 110425815
Myocardial infarction 57.23 18.14 123 162444 191960 110234772
Bone cancer 57.22 18.14 39 162528 2431 110424301
Pulmonary fibrosis 57.17 18.14 40 162527 102002 110324730
Unresponsive to stimuli 57.12 18.14 12 162555 63778 110362954
Rhinorrhoea 57.10 18.14 300 162267 102366 110324366
Psychotic disorder 56.36 18.14 5 162562 50932 110375800
Abdominal pain 56.15 18.14 483 162084 512506 109914226
Metastases to spine 56.05 18.14 53 162514 5290 110421442
Cardiogenic shock 55.17 18.14 9 162558 57329 110369403
Gait inability 54.80 18.14 72 162495 136304 110290428
Urinary tract infection 53.94 18.14 724 161843 325558 110101174
Insomnia 53.92 18.14 786 161781 359804 110066928
Foot deformity 53.00 18.14 5 162562 48475 110378257
Ventricular tachycardia 52.49 18.14 6 162561 50003 110376729
Colitis ulcerative 52.41 18.14 24 162543 77339 110349393
Toxic epidermal necrolysis 52.20 18.14 10 162557 56717 110370015
Pyrexia 51.96 18.14 969 161598 897296 109529436
Chest pain 51.87 18.14 332 162235 376043 110050689
Atrial fibrillation 51.04 18.14 170 162397 229472 110197260
Injection site swelling 50.67 18.14 14 162553 61776 110364956
Rectal haemorrhage 50.51 18.14 61 162506 119772 110306960
Melaena 50.34 18.14 19 162548 68738 110357994
Adrenal insufficiency 50.22 18.14 3 162564 42387 110384345
Lower limb fracture 50.08 18.14 24 162543 75324 110351408
Breast cancer recurrent 49.90 18.14 43 162524 3803 110422929
Hepatic lesion 49.86 18.14 62 162505 8431 110418301
Generalised tonic-clonic seizure 49.55 18.14 10 162557 54670 110372062
Hypomagnesaemia 48.91 18.14 14 162553 60356 110366376
Nail growth abnormal 48.39 18.14 21 162546 524 110426208
Shock 48.15 18.14 10 162557 53578 110373154
Lip dry 47.67 18.14 46 162521 100037 110326695
Thrombosis 47.62 18.14 298 162269 108364 110318368
Obstructive airways disorder 47.30 18.14 6 162561 46143 110380589
Respiratory distress 47.23 18.14 21 162546 68853 110357879
Eating disorder 47.09 18.14 125 162442 30733 110395999
Weight decreased 47.03 18.14 957 161610 467100 109959632
Drug level increased 47.03 18.14 7 162560 47712 110379020
Dyspepsia 47.01 18.14 458 162109 190507 110236225
Heart rate decreased 46.94 18.14 32 162535 82724 110344008
Hair growth abnormal 46.82 18.14 40 162527 3497 110423235
Adjustment disorder with depressed mood 46.73 18.14 5 162562 43878 110382854
Cardiac failure 46.60 18.14 132 162435 187494 110239238
Mental status changes 46.53 18.14 27 162540 76095 110350637
Blood pressure fluctuation 46.51 18.14 26 162541 74798 110351934
Sinusitis 46.01 18.14 252 162315 296436 110130296
Exostosis 44.70 18.14 7 162560 45949 110380783
Pulmonary thrombosis 44.42 18.14 76 162491 13787 110412945
Rash maculo-papular 44.42 18.14 27 162540 74195 110352537
Pulmonary hypertension 44.38 18.14 13 162554 55207 110371525
Angina pectoris 44.31 18.14 18 162549 62277 110364455
Product use in unapproved indication 44.26 18.14 432 162135 446945 109979787
Underdose 44.18 18.14 19 162548 63535 110363197
Hypersomnia 44.17 18.14 115 162452 27946 110398786
Adnexa uteri mass 44.13 18.14 19 162548 465 110426267
Aggression 43.95 18.14 16 162551 59194 110367538
Radiation injury 43.88 18.14 24 162543 1004 110425728
Urine odour abnormal 43.32 18.14 54 162513 7361 110419371
Tachypnoea 43.23 18.14 4 162563 39391 110387341
Tubulointerstitial nephritis 43.22 18.14 13 162554 54271 110372461
Rhabdomyolysis 43.03 18.14 69 162498 120332 110306400
Neutrophil count abnormal 42.91 18.14 45 162522 5087 110421645
Sinus tachycardia 42.77 18.14 7 162560 44486 110382246
Mastectomy 42.66 18.14 27 162540 1484 110425248
Lupus-like syndrome 42.55 18.14 5 162562 40787 110385945
Therapeutic response unexpected 42.02 18.14 102 162465 23741 110402991
Oophorectomy bilateral 41.96 18.14 12 162555 80 110426652
Malignant pleural effusion 41.79 18.14 40 162527 4053 110422679
Anaphylactic shock 41.67 18.14 12 162555 51534 110375198
Stevens-Johnson syndrome 41.63 18.14 9 162558 46892 110379840
Emotional distress 41.06 18.14 8 162559 44839 110381893
Lung disorder 40.89 18.14 132 162435 179915 110246817
Unevaluable event 40.71 18.14 18 162549 59209 110367523
Drug eruption 40.69 18.14 14 162553 53645 110373087
Renal failure 40.55 18.14 183 162384 226391 110200341
Ovarian disorder 40.52 18.14 19 162548 571 110426161
Flushing 40.35 18.14 57 162510 104679 110322053
Acute respiratory distress syndrome 40.13 18.14 14 162553 53184 110373548
Metastases to lymph nodes 39.99 18.14 76 162491 14956 110411776
Breast cancer 39.76 18.14 136 162431 38406 110388326
Off label use 39.66 18.14 1803 160764 1498382 108928350
Tooth disorder 39.55 18.14 114 162453 29395 110397337
Skin exfoliation 39.42 18.14 242 162325 87409 110339323
Cardiac failure congestive 39.17 18.14 104 162463 150896 110275836
Drug-induced liver injury 39.08 18.14 73 162494 119994 110306738
Aphthous ulcer 38.95 18.14 92 162475 21044 110405688
Metastases to skin 38.89 18.14 30 162537 2269 110424463
Circulatory collapse 38.67 18.14 8 162559 42985 110383747
Acute respiratory failure 37.73 18.14 33 162534 75227 110351505
Nasal discomfort 37.70 18.14 46 162521 6135 110420597
Hair disorder 37.67 18.14 23 162544 1186 110425546
Emotional disorder 37.32 18.14 77 162490 16083 110410649
Injection site haemorrhage 37.21 18.14 3 162564 33025 110393707
Cerebral haemorrhage 37.01 18.14 25 162542 64943 110361789
Metastases to eye 36.61 18.14 15 162552 323 110426409
Ventricular fibrillation 36.52 18.14 8 162559 41305 110385427
Toothache 36.48 18.14 96 162471 23479 110403253
Upper gastrointestinal haemorrhage 36.41 18.14 14 162553 50082 110376650
Injection site bruising 36.16 18.14 15 162552 51248 110375484
Staphylococcal infection 35.88 18.14 30 162537 69914 110356818
Heart rate increased 35.86 18.14 101 162466 143733 110282999
Muscular weakness 35.85 18.14 216 162351 248252 110178480
Poor quality product administered 35.82 18.14 39 162528 4602 110422130
Basal cell carcinoma 35.76 18.14 11 162556 45259 110381473
Knee arthroplasty 35.67 18.14 26 162541 64922 110361810
Sleep apnoea syndrome 35.42 18.14 8 162559 40439 110386293
Mitral valve incompetence 34.98 18.14 4 162563 33325 110393407
Tongue discomfort 34.88 18.14 31 162536 2857 110423875
Proteinuria 34.87 18.14 8 162559 40010 110386722
Back injury 34.86 18.14 13 162554 47386 110379346
Bone lesion 34.23 18.14 47 162520 7040 110419692
Weight increased 34.02 18.14 424 162143 419220 110007512
Haematoma 33.99 18.14 22 162545 58454 110368278
Hepatitis 33.72 18.14 50 162517 90004 110336728
Blood pressure diastolic decreased 33.72 18.14 6 162561 35879 110390853
Pleural neoplasm 33.68 18.14 15 162552 399 110426333
Abnormal behaviour 33.63 18.14 8 162559 39031 110387701
Red blood cell count abnormal 33.33 18.14 24 162543 1634 110425098
Dyskinesia 33.26 18.14 17 162550 51429 110375303
Respiratory depression 33.19 18.14 4 162563 31997 110394735
Pallor 33.16 18.14 21 162546 56446 110370286
Acute cutaneous lupus erythematosus 33.13 18.14 15 162552 415 110426317
Arrhythmia 33.11 18.14 32 162535 69543 110357189
Feeding disorder 33.07 18.14 87 162480 21275 110405457
Increased appetite 32.99 18.14 70 162497 14907 110411825
Tongue disorder 32.87 18.14 68 162499 14230 110412502
Faeces soft 32.74 18.14 59 162508 11151 110415581
Hypervolaemia 32.50 18.14 16 162551 49444 110377288
Adverse reaction 32.49 18.14 3 162564 29591 110397141
Withdrawal syndrome 32.35 18.14 4 162563 31376 110395356
Tremor 32.32 18.14 170 162397 202062 110224670
Treatment noncompliance 32.00 18.14 36 162531 72954 110353778
Body temperature increased 31.24 18.14 21 162546 54692 110372040
Nail discolouration 30.62 18.14 32 162535 3603 110423129
Hallucination, visual 30.61 18.14 10 162557 39595 110387137
Vulvovaginal dryness 30.26 18.14 28 162539 2719 110424013
Pancytopenia 30.15 18.14 454 162113 209159 110217573
Dental discomfort 30.15 18.14 15 162552 515 110426217
Metastases to retroperitoneum 30.06 18.14 14 162553 414 110426318
Gingival bleeding 29.90 18.14 80 162487 19759 110406973
Agranulocytosis 29.86 18.14 28 162539 61732 110365000
Hip arthroplasty 29.81 18.14 23 162544 55790 110370942
Metastases to bladder 29.75 18.14 13 162554 330 110426402
Dysphagia 29.69 18.14 351 162216 153249 110273483
No adverse event 29.64 18.14 39 162528 73800 110352932
Prehypertension 29.51 18.14 7 162560 19 110426713
Joint dislocation 29.47 18.14 7 162560 34183 110392549
Accidental overdose 29.45 18.14 20 162547 51814 110374918
Shock haemorrhagic 29.28 18.14 3 162564 27244 110399488
Blood calcium decreased 29.04 18.14 117 162450 35728 110391004
Pneumonitis 28.76 18.14 202 162365 76329 110350403
Neurotoxicity 28.73 18.14 13 162554 42194 110384538
Abdominal discomfort 28.64 18.14 770 161797 393088 110033644
Myalgia 28.34 18.14 472 162095 221909 110204823
Renal surgery 28.17 18.14 11 162556 208 110426524
Headache 28.09 18.14 1575 160992 880802 109545930
Sciatica 27.65 18.14 59 162508 92340 110334392
Onychomycosis 27.62 18.14 11 162556 38520 110388212
Electrocardiogram QT prolonged 27.54 18.14 76 162491 108884 110317848
Monocyte count decreased 27.38 18.14 31 162536 3820 110422912
Pancreatitis acute 27.23 18.14 29 162538 60245 110366487
Glomerular filtration rate decreased 27.14 18.14 99 162468 28857 110397875
Device malfunction 26.99 18.14 3 162564 25555 110401177
Loss of personal independence in daily activities 26.93 18.14 121 162446 149899 110276833
Eructation 26.79 18.14 62 162505 13995 110412737
Wrong technique in product usage process 26.79 18.14 55 162512 87293 110339439
Onychomadesis 26.79 18.14 17 162550 45646 110381086
Hypothyroidism 26.78 18.14 41 162526 72858 110353874
Tumour pain 26.59 18.14 27 162540 2940 110423792
Granulocyte count decreased 26.58 18.14 31 162536 3943 110422789
Myelodysplastic syndrome 26.38 18.14 11 162556 37473 110389259
Body height decreased 26.38 18.14 52 162515 10511 110416221
Oral herpes 26.28 18.14 114 162453 35966 110390766
Hospitalisation 26.14 18.14 114 162453 142379 110284353
Clostridium difficile colitis 26.09 18.14 16 162551 43762 110382970
Haematochezia 26.02 18.14 85 162482 115439 110311293
Product use complaint 26.00 18.14 30 162537 3773 110422959
Palpitations 25.91 18.14 133 162434 159079 110267653
Tongue blistering 25.83 18.14 22 162545 1915 110424817
Coagulopathy 25.74 18.14 14 162553 40897 110385835
Hallucination, auditory 25.72 18.14 4 162563 26393 110400339
Blood pressure decreased 25.70 18.14 85 162482 115006 110311726
Subdural haematoma 25.18 18.14 11 162556 36443 110390289
Hunger 24.95 18.14 39 162528 6565 110420167
Face oedema 24.92 18.14 9 162558 33460 110393272
Aspiration 24.88 18.14 7 162560 30526 110396206
Noninfective gingivitis 24.87 18.14 22 162545 2015 110424717
Metastases to central nervous system 24.85 18.14 82 162485 22735 110403997
Chronic obstructive pulmonary disease 24.80 18.14 80 162487 109078 110317654
Lip pain 24.76 18.14 24 162543 2470 110424262
Pain of skin 24.58 18.14 75 162492 19954 110406778
Metastases to the mediastinum 24.49 18.14 15 162552 778 110425954
Myocarditis 24.29 18.14 7 162560 30048 110396684
Vision blurred 24.13 18.14 293 162274 128729 110298003
Oral disorder 24.05 18.14 54 162513 11949 110414783
Chronic sinusitis 23.99 18.14 4 162563 25080 110401652
Cyanosis 23.90 18.14 7 162560 29734 110396998
Disorientation 23.86 18.14 42 162525 70629 110356103
Chapped lips 23.64 18.14 26 162541 3102 110423630
Hypogeusia 23.53 18.14 22 162545 2165 110424567
Nightmare 23.45 18.14 14 162553 38849 110387883
Bacteraemia 23.24 18.14 17 162550 42373 110384359
Metastases to spinal cord 23.21 18.14 10 162557 245 110426487
Ascites 23.03 18.14 223 162344 92585 110334147
Basophil count increased 23.00 18.14 20 162547 1790 110424942
Eastern Cooperative Oncology Group performance status worsened 23 18.14 25 162542 2944 110423788
Nephropathy toxic 22.96 18.14 6 162561 27472 110399260
Haemorrhage intracranial 22.95 18.14 7 162560 28962 110397770
Acidosis 22.92 18.14 3 162564 22528 110404204
Mucosal inflammation 22.88 18.14 229 162338 95912 110330820
Metastases to kidney 22.80 18.14 13 162554 590 110426142
Haemoptysis 22.68 18.14 44 162523 71310 110355422
Metastases to pleura 22.67 18.14 21 162546 2042 110424690
Joint neoplasm 22.64 18.14 7 162560 63 110426669
Red cell distribution width increased 22.63 18.14 67 162500 17535 110409197
Ataxia 22.58 18.14 8 162559 30100 110396632
Ovarian cancer 22.52 18.14 30 162537 4366 110422366
Dermatitis atopic 22.47 18.14 5 162562 25536 110401196
Parkinsonism 22.46 18.14 3 162564 22184 110404548
Hyperaesthesia teeth 22.41 18.14 22 162545 2300 110424432
Infusion site coldness 22.35 18.14 10 162557 269 110426463
Oophorectomy 21.99 18.14 11 162556 382 110426350
Breast haemorrhage 21.87 18.14 9 162558 196 110426536
Nasal disorder 21.85 18.14 29 162538 4205 110422527
Respiratory disorder 21.84 18.14 45 162522 71337 110355395
Oesophageal pain 21.82 18.14 32 162535 5093 110421639
Transient ischaemic attack 21.63 18.14 38 162529 63944 110362788
Labelled drug-drug interaction medication error 21.61 18.14 8 162559 29294 110397438
Metastases to chest wall 21.42 18.14 13 162554 663 110426069
Cardiomegaly 21.40 18.14 8 162559 29122 110397610
Feeling of body temperature change 21.26 18.14 35 162532 6153 110420579
Bone disorder 21.18 18.14 74 162493 21118 110405614
Toxic skin eruption 21.17 18.14 7 162560 27508 110399224
Splenomegaly 21.14 18.14 5 162562 24493 110402239
Metastases to pelvis 21.05 18.14 14 162553 838 110425894
Menopausal symptoms 21.04 18.14 22 162545 2479 110424253
Blood potassium decreased 21.02 18.14 144 162423 53970 110372762
Migraine 20.86 18.14 157 162410 171495 110255237
Product label confusion 20.86 18.14 4 162563 22673 110404059
Radiation fibrosis 20.85 18.14 6 162561 41 110426691
Retching 20.80 18.14 77 162490 22605 110404127
Radiation fibrosis - lung 20.76 18.14 7 162560 85 110426647
Joint effusion 20.75 18.14 3 162564 20902 110405830
Muscle twitching 20.73 18.14 9 162558 29926 110396806
Inappropriate antidiuretic hormone secretion 20.70 18.14 12 162555 33839 110392893
Poor quality sleep 20.67 18.14 89 162478 27988 110398744
Activated partial thromboplastin time prolonged 20.46 18.14 4 162563 22364 110404368
Diabetes mellitus 20.44 18.14 76 162491 99305 110327427
Increased tendency to bruise 20.40 18.14 50 162517 11708 110415024
Liver disorder 20.33 18.14 124 162443 142119 110284613
Tumour lysis syndrome 20.18 18.14 10 162557 30791 110395941
Cerebral infarction 20.18 18.14 28 162539 51810 110374922
Infection 20.16 18.14 393 162174 361807 110064925
Neoplasm 20.15 18.14 48 162519 11039 110415693
Nail avulsion 20.07 18.14 8 162559 160 110426572
Retracted nipple 20.02 18.14 5 162562 18 110426714
Walking aid user 19.97 18.14 6 162561 25069 110401663
Progressive multifocal leukoencephalopathy 19.83 18.14 6 162561 24950 110401782
Thrombotic microangiopathy 19.81 18.14 9 162558 29140 110397592
Renal tubular necrosis 19.81 18.14 10 162557 30465 110396267
Skin sensitisation 19.80 18.14 15 162552 1104 110425628
Injection site rash 19.78 18.14 5 162562 23414 110403318
Schizophrenia 19.76 18.14 4 162563 21822 110404910
Lip exfoliation 19.71 18.14 13 162554 767 110425965
Hypogammaglobulinaemia 19.66 18.14 3 162564 20073 110406659
Acute generalised exanthematous pustulosis 19.55 18.14 4 162563 21660 110405072
Soft tissue neoplasm 19.54 18.14 7 162560 103 110426629
Bronchospasm 19.54 18.14 10 162557 30229 110396503
Pulmonary arterial hypertension 19.28 18.14 12 162555 32556 110394176
Diabetic ketoacidosis 19.26 18.14 20 162547 42038 110384694
Pruritus 19.23 18.14 1042 161525 580518 109846214
Supraventricular tachycardia 19.17 18.14 6 162561 24416 110402316
Thyroid calcification 19.12 18.14 6 162561 57 110426675
Haematocrit decreased 19.01 18.14 164 162403 65953 110360779
Atrial flutter 18.97 18.14 6 162561 24256 110402476
Gamma-glutamyltransferase decreased 18.90 18.14 10 162557 391 110426341
Chills 18.88 18.14 389 162178 190191 110236541
Hemiparesis 18.87 18.14 22 162545 43881 110382851
Hyperlipidaemia 18.85 18.14 15 162552 35833 110390899
Oesophageal stenosis 18.82 18.14 30 162537 5135 110421597
Skin ulcer 18.74 18.14 41 162526 63604 110363128
Blood triglycerides increased 18.56 18.14 6 162561 23920 110402812
Swollen tongue 18.52 18.14 38 162529 60324 110366408
Myocardial ischaemia 18.51 18.14 8 162559 26676 110400056
Restlessness 18.49 18.14 34 162533 56225 110370507
Foreign body in throat 18.26 18.14 14 162553 1049 110425683
Aphasia 18.22 18.14 37 162530 58960 110367772
Tooth extraction 18.20 18.14 51 162516 12940 110413792

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EF01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Cyclin-dependent kinase (CDK) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:82665 EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L01EF Cyclin-dependent kinase (CDK) inhibitors 2 drugs
abemaciclibribociclib

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

DiseaseRelationSNOMED_IDDOID
Hormone receptor positive malignant neoplasm of breast indication 417181009
Human epidermal growth factor 2 negative carcinoma of breast indication 431396003




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.03 Basic
pKa2 7.08 Basic
pKa3 5.81 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG IBRANCE PFIZER N207103 Feb. 3, 2015 RX CAPSULE ORAL Sept. 16, 2028 ADDITIONAL CLINICAL TRIAL INFORMATION ADDED TO PEDIATRIC USE SUBSECTION
125MG IBRANCE PFIZER N207103 Feb. 3, 2015 RX CAPSULE ORAL Sept. 16, 2028 ADDITIONAL CLINICAL TRIAL INFORMATION ADDED TO PEDIATRIC USE SUBSECTION
75MG IBRANCE PFIZER N207103 Feb. 3, 2015 RX CAPSULE ORAL Sept. 16, 2028 ADDITIONAL CLINICAL TRIAL INFORMATION ADDED TO PEDIATRIC USE SUBSECTION
100MG IBRANCE PFIZER N212436 Nov. 1, 2019 RX TABLET ORAL Sept. 16, 2028 ADDITIONAL CLINICAL TRIAL INFORMATION ADDED TO PEDIATRIC USE SUBSECTION
125MG IBRANCE PFIZER N212436 Nov. 1, 2019 RX TABLET ORAL Sept. 16, 2028 ADDITIONAL CLINICAL TRIAL INFORMATION ADDED TO PEDIATRIC USE SUBSECTION
75MG IBRANCE PFIZER N212436 Nov. 1, 2019 RX TABLET ORAL Sept. 16, 2028 ADDITIONAL CLINICAL TRIAL INFORMATION ADDED TO PEDIATRIC USE SUBSECTION
100MG IBRANCE PFIZER N207103 Feb. 3, 2015 RX CAPSULE ORAL March 16, 2029 PEDIATRIC EXCLUSIVITY
125MG IBRANCE PFIZER N207103 Feb. 3, 2015 RX CAPSULE ORAL March 16, 2029 PEDIATRIC EXCLUSIVITY
75MG IBRANCE PFIZER N207103 Feb. 3, 2015 RX CAPSULE ORAL March 16, 2029 PEDIATRIC EXCLUSIVITY
100MG IBRANCE PFIZER N212436 Nov. 1, 2019 RX TABLET ORAL March 16, 2029 PEDIATRIC EXCLUSIVITY
125MG IBRANCE PFIZER N212436 Nov. 1, 2019 RX TABLET ORAL March 16, 2029 PEDIATRIC EXCLUSIVITY
75MG IBRANCE PFIZER N212436 Nov. 1, 2019 RX TABLET ORAL March 16, 2029 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Cyclin-dependent kinase 6 Kinase INHIBITOR IC50 7.82 SCIENTIFIC LITERATURE DRUG LABEL
Cyclin-dependent kinase 4 Kinase INHIBITOR IC50 7.96 SCIENTIFIC LITERATURE DRUG LABEL
Receptor-type tyrosine-protein kinase FLT3 Kinase IC50 5.46 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Enzyme EC50 5.47 CHEMBL
Poly [ADP-ribose] polymerase 1 Enzyme IC50 8.46 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit delta Kinase IC50 6.21 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit gamma Kinase IC50 5.03 CHEMBL
AP2-associated protein kinase 1 Kinase Kd 5.38 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit beta Kinase IC50 5.80 CHEMBL
Serine/threonine-protein kinase 16 Kinase Kd 5 CHEMBL
BMP-2-inducible protein kinase Kinase Kd 4.58 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 6.56 CHEMBL
Glycogen synthase kinase-3 beta Kinase IC50 4.95 CHEMBL
Cyclin-dependent kinase 16 Kinase Kd 5.56 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.54 CHEMBL
Cyclin-dependent kinase 9 Kinase IC50 6.10 CHEMBL
Cyclin-dependent kinase 17 Kinase Kd 5.90 CHEMBL
Tyrosine-protein kinase JAK3 Kinase IC50 7.20 CHEMBL
Casein kinase II subunit alpha' Kinase Kd 6.31 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 4 Kinase Kd 5.90 CHEMBL
Serine/threonine-protein kinase D2 Kinase Kd 5.25 CHEMBL
Serine/threonine-protein kinase D3 Kinase Kd 4.79 CHEMBL
Serine/threonine-protein kinase TAO3 Kinase Kd 4.80 CHEMBL
Serine/threonine-protein kinase TAO2 Kinase Kd 4.55 CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma Kinase Kd 5.76 CHEMBL
Cyclin-dependent kinase 4/cyclin D1 Kinase IC50 8.70 CHEMBL
CDK2/Cyclin A Kinase IC50 6.64 CHEMBL
CDK6/cyclin D1 Kinase IC50 8.42 CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha Kinase Kd 6.68 CHEMBL
Uncharacterized protein FLJ45252 Unclassified Kd 4.56 CHEMBL
Ribosomal protein S6 kinase alpha-1 Kinase INHIBITOR IC50 5.10 SCIENTIFIC LITERATURE
Dual specificity tyrosine-phosphorylation-regulated kinase 1A Kinase INHIBITOR IC50 5.70 SCIENTIFIC LITERATURE
Casein kinase II subunit alpha Kinase Kd 6.12 CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase Enzyme EC50 5.54 CHEMBL

External reference:

IDSource
G9ZF61LE7G UNII
D10372 KEGG_DRUG
4034136 VUID
N0000191426 NUI
827022-33-3 SECONDARY_CAS_RN
4034136 VANDF
C3853822 UMLSCUI
CHEBI:85993 CHEBI
LQQ PDB_CHEM_ID
CHEMBL189963 ChEMBL_ID
5330286 PUBCHEM_CID
DB09073 DRUGBANK_ID
CHEMBL2364621 ChEMBL_ID
9802 INN_ID
C500026 MESH_SUPPLEMENTAL_RECORD_UI
7380 IUPHAR_LIGAND_ID
1601374 RXNORM
232484 MMSL
30872 MMSL
d08342 MMSL
015881 NDDF
715958001 SNOMEDCT_US
763549001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 0069-0187 CAPSULE 75 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 0069-0188 CAPSULE 100 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 0069-0189 CAPSULE 125 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 0069-0284 TABLET, FILM COATED 75 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 0069-0486 TABLET, FILM COATED 100 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 0069-0688 TABLET, FILM COATED 125 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 63539-284 TABLET, FILM COATED 75 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 63539-486 TABLET, FILM COATED 100 mg ORAL NDA 32 sections
Ibrance HUMAN PRESCRIPTION DRUG LABEL 1 63539-688 TABLET, FILM COATED 125 mg ORAL NDA 32 sections