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

Stem definitionDrug idCAS RN
phosphodiesterase IV (PDE IV) inhibitors 4829 608141-41-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • apremilast
  • CC-10004
  • otezla
Apremilast is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. The specific mechanism(s) by which apremilast exerts its therapeutic action in psoriatic arthritis patients and psoriasis patients is not well defined.
  • Molecular weight: 460.50
  • Formula: C22H24N2O7S
  • CLOGP: 1.46
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 1
  • TPSA: 119.08
  • ALOGS: -4.13
  • ROTB: 8

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
60 mg O

ADMET properties:

PropertyValueReference
CL (Clearance) 2.38 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.32 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 6.03 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 20, 2019 PMDA Celgene K.K.
March 21, 2014 FDA CELGENE CORP
Nov. 20, 2014 EMA

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
Psoriasis 18840.35 26.16 7084 107601 71520 46499857
Diarrhoea 10405.22 26.16 9434 105251 550168 46021209
Nausea 8890.80 26.16 9509 105176 677945 45893432
Headache 6846.76 26.16 7015 107670 471337 46100040
Product dose omission issue 5603.74 26.16 4026 110659 164494 46406883
Psoriatic arthropathy 4853.71 26.16 2168 112517 34211 46537166
Abdominal discomfort 2545.71 26.16 2441 112244 148724 46422653
Drug ineffective 1773.73 26.16 4596 110089 673242 45898135
Adverse drug reaction 1302.46 26.16 988 113697 43374 46528003
Depression 1147.55 26.16 1726 112959 168378 46402999
Therapy non-responder 800.23 26.16 722 113963 40430 46530947
Abdominal pain upper 751.58 26.16 1308 113377 143997 46427380
Weight decreased 726.56 26.16 1599 113086 209250 46362127
Gastric disorder 600.33 26.16 509 114176 26196 46545181
Frequent bowel movements 558.82 26.16 362 114323 12270 46559107
Migraine 550.14 26.16 765 113920 69261 46502116
Acute kidney injury 542.90 26.16 7 114678 235848 46335529
Toxicity to various agents 475.84 26.16 9 114676 211757 46359620
Dyspnoea 463.60 26.16 355 114330 515193 46056184
Anaemia 431.18 26.16 59 114626 255720 46315657
Hypotension 395.91 26.16 52 114633 232537 46338840
Rash 382.90 26.16 1809 112876 354703 46216674
Drug interaction 366.58 26.16 37 114648 203057 46368320
Dyspepsia 355.30 26.16 618 114067 67854 46503523
Pyrexia 338.14 26.16 221 114464 348581 46222796
Neutropenia 326.04 26.16 5 114680 143199 46428178
Tension headache 322.78 26.16 149 114536 2525 46568852
Thrombocytopenia 285.71 26.16 5 114680 126576 46444801
Vomiting 275.09 26.16 1976 112709 450818 46120559
Stress 273.52 26.16 470 114215 51081 46520296
Gastrointestinal disorder 261.20 26.16 500 114185 59076 46512301
Confusional state 255.19 26.16 43 114642 159849 46411528
Insomnia 236.72 26.16 915 113770 164009 46407368
Haemoglobin decreased 236.47 26.16 22 114663 128927 46442450
Oedema peripheral 220.14 26.16 60 114625 159646 46411731
Exposure during pregnancy 220.07 26.16 11 114674 108201 46463176
Faeces soft 217.31 26.16 124 114561 3324 46568053
Overdose 211.83 26.16 9 114676 101970 46469407
Therapeutic response decreased 210.24 26.16 379 114306 42766 46528611
White blood cell count decreased 206.16 26.16 19 114666 112212 46459165
Upper respiratory tract infection 202.32 26.16 468 114217 63088 46508289
Fall 199.50 26.16 313 114372 328784 46242593
Death 198.84 26.16 324 114361 335224 46236153
Therapeutic product effect decreased 195.90 26.16 544 114141 82057 46489320
Cardiac arrest 194.60 26.16 6 114679 90393 46480984
Pancytopenia 193.40 26.16 3 114682 85055 46486322
Pneumonia 193.09 26.16 397 114288 375923 46195454
Pleural effusion 188.29 26.16 3 114682 82949 46488428
Sepsis 185.74 26.16 52 114633 135962 46435415
Seizure 181.69 26.16 40 114645 123014 46448363
Respiratory failure 176.99 26.16 15 114670 94801 46476576
Platelet count decreased 175.76 26.16 20 114665 100004 46471373
Asthenia 174.48 26.16 311 114374 310764 46260613
Maternal exposure during pregnancy 167.09 26.16 26 114659 102523 46468854
Pulmonary embolism 160.89 26.16 35 114650 108550 46462827
Renal failure 155.87 26.16 43 114642 113551 46457826
Disease progression 151.38 26.16 22 114663 91278 46480099
Loss of consciousness 150.34 26.16 40 114645 108198 46463179
Enthesopathy 149.76 26.16 110 114575 4580 46566797
Leukopenia 145.43 26.16 5 114680 68338 46503039
Arthralgia 144.59 26.16 1448 113237 363155 46208222
Deep vein thrombosis 142.56 26.16 15 114670 79758 46491619
Intentional overdose 140.90 26.16 4 114681 64940 46506437
Malignant neoplasm progression 140.85 26.16 4 114681 64922 46506455
Syncope 139.50 26.16 42 114643 104761 46466616
Product supply issue 138.40 26.16 59 114626 819 46570558
Oxygen saturation decreased 137.57 26.16 8 114677 69156 46502221
Drug hypersensitivity 135.49 26.16 245 114440 243580 46327797
Decreased appetite 130.01 26.16 868 113817 192968 46378409
Coma 128.82 26.16 3 114682 58346 46513031
Unevaluable event 128.63 26.16 323 114362 45852 46525525
Tachycardia 125.40 26.16 44 114641 99578 46471799
Injection site pain 122.30 26.16 55 114630 107097 46464280
Cardiac failure 119.99 26.16 25 114660 79923 46491454
Off label use 119.47 26.16 504 114181 379337 46192040
Injection site erythema 118.69 26.16 20 114665 74407 46496970
Somnolence 114.90 26.16 129 114556 156392 46414985
Cardiac failure congestive 114.66 26.16 41 114644 91709 46479668
Hypoxia 113.16 26.16 3 114682 51835 46519542
Chest pain 113.13 26.16 161 114524 176163 46395214
Multiple organ dysfunction syndrome 112.86 26.16 3 114682 51707 46519670
Septic shock 111.27 26.16 8 114677 57885 46513492
Hyperkalaemia 110.45 26.16 3 114682 50706 46520671
Product use in unapproved indication 110.01 26.16 42 114643 90231 46481146
Pruritus 109.00 26.16 989 113696 241363 46330014
Flatulence 108.08 26.16 227 114458 28651 46542726
Therapeutic product effect incomplete 104.96 26.16 425 114260 77728 46493649
Infusion related reaction 104.91 26.16 59 114626 101149 46470228
Gastrointestinal haemorrhage 101.16 26.16 32 114653 77341 46494036
Dehydration 101.03 26.16 147 114538 159393 46411984
Oedema 100.59 26.16 21 114664 67050 46504327
Hypoglycaemia 100.30 26.16 9 114676 54340 46517037
Atrial fibrillation 98.21 26.16 67 114618 103523 46467854
Neuropathy peripheral 97.10 26.16 51 114634 90842 46480535
Plasma cell myeloma 95.53 26.16 3 114682 44475 46526902
Interstitial lung disease 89.41 26.16 13 114672 53936 46517441
Mood altered 87.25 26.16 132 114553 12875 46558502
Pulmonary oedema 85.42 26.16 12 114673 51093 46520284
Hypertension 84.54 26.16 227 114458 196129 46375248
Blood alkaline phosphatase increased 83.90 26.16 3 114682 39606 46531771
Mucosal inflammation 82.39 26.16 3 114682 38973 46532404
Anaphylactic reaction 80.95 26.16 16 114669 53096 46518281
Dysphagia 80.21 26.16 45 114640 77267 46494110
Rebound psoriasis 79.78 26.16 21 114664 50 46571327
Nasopharyngitis 79.38 26.16 648 114037 153350 46418027
Tenosynovitis 79.12 26.16 95 114590 7420 46563957
Alanine aminotransferase increased 78.90 26.16 61 114624 88390 46482987
Muscle spasms 78.66 26.16 545 114140 122568 46448809
Product use issue 78.58 26.16 70 114615 94574 46476803
Delirium 78.23 26.16 3 114682 37225 46534152
Ascites 76.70 26.16 3 114682 36581 46534796
Pulmonary hypertension 75.30 26.16 3 114682 35990 46535387
Mental status changes 73.95 26.16 5 114680 38083 46533294
Weight increased 70.88 26.16 190 114495 164283 46407094
Pemphigus 70.35 26.16 13 114672 45261 46526116
Hyperglycaemia 69.90 26.16 4 114681 35067 46536310
Muscular weakness 69.22 26.16 74 114611 91770 46479607
Blood creatinine increased 69.02 26.16 52 114633 76351 46495026
Liver function test abnormal 68.79 26.16 15 114670 46472 46524905
Paraesthesia 67.85 26.16 115 114570 117322 46454055
Dysarthria 67.11 26.16 7 114678 37491 46533886
Cerebrovascular accident 67.01 26.16 90 114595 100949 46470428
Balance disorder 66.29 26.16 38 114647 64483 46506894
Dyspnoea exertional 65.37 26.16 21 114664 50268 46521109
Pneumonia aspiration 64.90 26.16 3 114682 31602 46539775
Influenza 64.76 26.16 408 114277 88862 46482515
Aspartate aminotransferase increased 64.38 26.16 59 114626 78641 46492736
Blood pressure decreased 64.16 26.16 30 114655 57129 46514248
Coronary artery disease 63.90 26.16 5 114680 33747 46537630
Injury 63.56 26.16 15 114670 44012 46527365
Multiple sclerosis relapse 63.55 26.16 13 114672 42112 46529265
Injection site pruritus 62.65 26.16 11 114674 39732 46531645
Flushing 62.29 26.16 41 114644 64573 46506804
Systemic lupus erythematosus 61.97 26.16 42 114643 65138 46506239
Femur fracture 61.10 26.16 9 114676 36988 46534389
Chronic kidney disease 60.86 26.16 13 114672 40858 46530519
Hepatic failure 60.42 26.16 6 114679 33410 46537967
Injection site swelling 59.70 26.16 13 114672 40314 46531063
Respiratory distress 59.66 26.16 5 114680 31911 46539466
Hallucination 59.59 26.16 24 114661 49927 46521450
Acute respiratory failure 59.08 26.16 3 114682 29135 46542242
Myocardial infarction 58.67 26.16 93 114592 97435 46473942
Glossodynia 58.62 26.16 18 114667 44355 46527022
Dyskinesia 58.58 26.16 3 114682 28922 46542455
Renal impairment 58.22 26.16 58 114627 74314 46497063
Angioedema 57.60 26.16 13 114672 39329 46532048
Adverse reaction 56.97 26.16 84 114601 8006 46563371
Cognitive disorder 56.44 26.16 11 114674 36872 46534505
Thrombosis 56.22 26.16 34 114651 56035 46515342
Vision blurred 55.96 26.16 68 114617 79640 46491737
Intentional product use issue 55.79 26.16 30 114655 52750 46518627
Fluid retention 55.46 26.16 28 114657 51018 46520359
Hepatitis 55.18 26.16 7 114678 32208 46539169
No adverse event 55.00 26.16 9 114676 34222 46537155
Lower respiratory tract infection 54.41 26.16 34 114651 55055 46516322
Discomfort 54.26 26.16 243 114442 46427 46524950
Drug reaction with eosinophilia and systemic symptoms 54.23 26.16 5 114680 29543 46541834
Heart rate decreased 54.08 26.16 7 114678 31716 46539661
Gastrooesophageal reflux disease 54.05 26.16 340 114345 74004 46497373
Red blood cell count decreased 53.73 26.16 8 114677 32615 46538762
Blood creatine phosphokinase increased 52.78 26.16 4 114681 27720 46543657
Medication error 52.27 26.16 7 114678 30904 46540473
Sinus headache 52.10 26.16 61 114624 4639 46566738
Suicide attempt 51.60 26.16 36 114649 55000 46516377
Osteonecrosis 51.11 26.16 3 114682 25741 46545636
Disorientation 50.56 26.16 14 114671 36904 46534473
Arthritis 50.37 26.16 344 114341 76972 46494405
Haematoma 49.85 26.16 9 114676 31863 46539514
Gamma-glutamyltransferase increased 49.56 26.16 9 114676 31731 46539646
Aphasia 49.44 26.16 6 114679 28561 46542816
Hepatotoxicity 49.39 26.16 3 114682 25006 46546371
Gait disturbance 49.13 26.16 187 114498 145076 46426301
Bone erosion 48.60 26.16 85 114600 9358 46562019
Visual impairment 47.76 26.16 56 114629 66633 46504744
Melaena 47.65 26.16 6 114679 27766 46543611
Chills 47.63 26.16 103 114582 95929 46475448
Blood urea increased 47.31 26.16 4 114681 25348 46546029
Hepatic function abnormal 47.24 26.16 13 114672 34408 46536969
Agitation 47.18 26.16 40 114645 55375 46516002
Chest discomfort 47.14 26.16 94 114591 90175 46481202
Urinary incontinence 46.98 26.16 7 114678 28523 46542854
Urinary retention 46.29 26.16 5 114680 26056 46545321
Pancreatitis acute 46.21 26.16 4 114681 24868 46546509
White blood cell count increased 45.48 26.16 26 114659 44193 46527184
Lymphocyte count decreased 45.22 26.16 5 114680 25584 46545793
Memory impairment 45.09 26.16 335 114350 77002 46494375
Haemorrhage 45.03 26.16 41 114644 54828 46516549
Epistaxis 44.99 26.16 55 114630 64250 46507127
Hypoaesthesia 44.90 26.16 146 114539 118723 46452654
Hypothyroidism 44.60 26.16 11 114674 31327 46540050
Hand deformity 43.95 26.16 15 114670 34559 46536818
Rash maculo-papular 43.31 26.16 8 114677 27866 46543511
Haematuria 43.29 26.16 7 114678 26851 46544526
Sinusitis 43.08 26.16 498 114187 129270 46442107
Swelling 42.93 26.16 159 114526 124352 46447025
Cerebral infarction 42.76 26.16 4 114681 23362 46548015
Cerebral haemorrhage 42.29 26.16 9 114676 28362 46543015
Speech disorder 42.13 26.16 18 114667 36149 46535228
Blood sodium decreased 41.75 26.16 3 114682 21723 46549654
Impaired healing 41.68 26.16 19 114666 36724 46534653
Hospitalisation 41.47 26.16 57 114628 63328 46508049
Abortion spontaneous 40.33 26.16 29 114656 43617 46527760
Erythema 40.25 26.16 197 114488 142623 46428754
Red blood cell sedimentation rate 40.23 26.16 34 114651 1739 46569638
Palmoplantar pustulosis 40.17 26.16 19 114666 341 46571036
Device related infection 40.16 26.16 3 114682 21038 46550339
Exostosis 39.94 26.16 82 114603 10181 46561196
Visual acuity reduced 39.90 26.16 4 114681 22109 46549268
Pallor 39.76 26.16 5 114680 23161 46548216
Rhinorrhoea 39.10 26.16 225 114460 47440 46523937
Epilepsy 38.68 26.16 6 114679 23732 46547645
Asthma 38.47 26.16 107 114578 91435 46479942
Lung disorder 38.43 26.16 30 114655 43274 46528103
Rheumatoid arthritis 38.34 26.16 391 114294 239824 46331553
Injection site bruising 38.03 26.16 20 114665 35616 46535761
Cholelithiasis 38.02 26.16 24 114661 38657 46532720
Therapy partial responder 37.97 26.16 52 114633 4630 46566747
Gastroenteritis viral 37.75 26.16 114 114571 18005 46553372
Stevens-Johnson syndrome 37.71 26.16 6 114679 23291 46548086
Mood swings 37.45 26.16 106 114579 16146 46555231
Joint dislocation 37.36 26.16 84 114601 11102 46560275
Constipation 36.92 26.16 263 114422 173834 46397543
Blood potassium decreased 36.89 26.16 24 114661 38039 46533338
Joint stiffness 36.82 26.16 148 114537 26960 46544417
Metastases to liver 36.80 26.16 3 114682 19582 46551795
Arrhythmia 36.53 26.16 20 114665 34821 46536556
Aggression 36.49 26.16 6 114679 22738 46548639
Circulatory collapse 36.31 26.16 5 114680 21619 46549758
Wheezing 35.95 26.16 47 114638 53339 46518038
Haemoptysis 35.73 26.16 10 114675 26179 46545198
Skin exfoliation 35.69 26.16 168 114517 32770 46538607
Transient ischaemic attack 35.22 26.16 21 114664 34882 46536495
Pneumonitis 34.98 26.16 13 114672 28407 46542970
Blood parathyroid hormone decreased 34.54 26.16 48 114637 4333 46567044
Injection site reaction 34.45 26.16 40 114645 47809 46523568
Dry skin 33.89 26.16 194 114491 40822 46530555
Loss of personal independence in daily activities 33.49 26.16 248 114437 56935 46514442
Sleep apnoea syndrome 33.18 26.16 7 114678 22194 46549183
Hallucination, visual 32.86 26.16 3 114682 17870 46553507
Abnormal behaviour 32.81 26.16 6 114679 21052 46550325
Blood pressure fluctuation 32.62 26.16 17 114668 30431 46540946
Orthostatic hypotension 32.57 26.16 10 114675 24648 46546729
Malaise 32.17 26.16 1052 113633 330180 46241197
Urinary tract infection 32.14 26.16 366 114319 219900 46351477
Psychotic disorder 32.07 26.16 8 114677 22613 46548764
Rash pruritic 31.99 26.16 202 114483 44013 46527364
Granuloma skin 31.93 26.16 41 114644 3429 46567948
Defaecation urgency 31.89 26.16 36 114649 2631 46568746
Chronic obstructive pulmonary disease 31.85 26.16 58 114627 57575 46513802
Rash macular 31.84 26.16 112 114573 19148 46552229
Dactylitis 31.52 26.16 25 114660 1168 46570209
Lethargy 31.52 26.16 48 114637 51123 46520254
Multiple allergies 31.20 26.16 61 114624 7310 46564067
Accidental exposure to product 30.79 26.16 7 114678 21074 46550303
Intestinal obstruction 30.33 26.16 13 114672 26062 46545315
General physical health deterioration 30.17 26.16 164 114521 115605 46455772
Proteinuria 29.85 26.16 3 114682 16550 46554827
Tongue disorder 29.72 26.16 59 114626 7151 46564226
Swelling face 29.67 26.16 53 114632 53006 46518371
Underdose 29.57 26.16 6 114679 19552 46551825
Hepatic enzyme increased 29.14 26.16 103 114582 81684 46489693
Adverse event 29.11 26.16 163 114522 34021 46537356
Electrolyte imbalance 28.89 26.16 4 114681 17222 46554155
Cardiomyopathy 28.76 26.16 3 114682 16070 46555307
Amnesia 28.70 26.16 36 114649 41595 46529782
Withdrawal syndrome 28.62 26.16 5 114680 18129 46553248
Alopecia 28.27 26.16 558 114127 161856 46409521
Therapy cessation 28.25 26.16 135 114550 26494 46544883
Dandruff 28.18 26.16 12 114673 166 46571211
Wrong technique in product usage process 28.12 26.16 57 114628 54365 46517012
Blood calcium decreased 27.85 26.16 3 114682 15670 46555707
Bowel movement irregularity 27.71 26.16 38 114647 3387 46567990
Pregnancy 27.65 26.16 136 114549 27001 46544376
Panniculitis 27.62 26.16 50 114635 5654 46565723
Mobility decreased 27.61 26.16 68 114617 60526 46510851
COVID-19 27.32 26.16 104 114581 18471 46552906
Contraindicated product administered 26.96 26.16 103 114582 79844 46491533
Drug resistance 26.95 26.16 5 114680 17363 46554014
Injection site haemorrhage 26.29 26.16 9 114676 20700 46550677
Sinus disorder 26.26 26.16 95 114590 16468 46554909

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
Psoriasis 11562.56 34.13 3889 50588 38617 29859384
Diarrhoea 6345.05 34.13 5007 49470 329096 29568905
Headache 3829.10 34.13 2921 51556 179385 29718616
Product dose omission issue 3805.40 34.13 2247 52230 89384 29808617
Nausea 3408.32 34.13 3366 51111 293591 29604410
Abdominal discomfort 2842.77 34.13 1498 52979 47293 29850708
Drug ineffective 2368.01 34.13 2976 51501 337411 29560590
Psoriatic arthropathy 2314.15 34.13 922 53555 14839 29883162
Depression 819.75 34.13 912 53565 89525 29808476
Adverse drug reaction 818.83 34.13 515 53962 22630 29875371
Abdominal pain upper 665.15 34.13 687 53790 61864 29836137
Therapy non-responder 610.26 34.13 472 54005 28981 29869020
Weight decreased 524.57 34.13 963 53514 149958 29748043
Frequent bowel movements 524.05 34.13 271 54206 8134 29889867
Therapeutic product effect decreased 504.44 34.13 420 54057 28656 29869345
Gastric disorder 414.20 34.13 251 54226 10292 29887709
Acute kidney injury 406.41 34.13 23 54454 273819 29624182
Rash 315.97 34.13 912 53565 190977 29707024
Drug interaction 289.01 34.13 19 54458 199549 29698452
Anaemia 278.53 34.13 28 54449 207964 29690037
Hypotension 265.95 34.13 28 54449 200537 29697464
Faeces soft 262.00 34.13 111 54366 2088 29895913
Gastrointestinal disorder 259.54 34.13 287 54190 27850 29870151
Therapeutic response decreased 257.43 34.13 267 54210 24082 29873919
Pyrexia 253.16 34.13 110 54367 294379 29603622
Dyspepsia 217.58 34.13 272 54205 30057 29867944
Dyspnoea 202.08 34.13 186 54291 333109 29564892
Thrombocytopenia 195.45 34.13 14 54463 137030 29760971
Arthralgia 186.11 34.13 606 53871 135185 29762816
Flatulence 183.01 34.13 194 54283 17935 29880066
Tension headache 176.75 34.13 72 54405 1221 29896780
Pneumonia 175.17 34.13 211 54266 334095 29563906
Febrile neutropenia 167.52 34.13 6 54471 106687 29791314
Mood altered 161.51 34.13 128 54349 8122 29889879
Respiratory failure 156.83 34.13 6 54471 100636 29797365
Haemoglobin decreased 156.12 34.13 14 54463 114084 29783917
Therapeutic product effect incomplete 155.35 34.13 245 54232 33589 29864412
Confusional state 146.46 34.13 33 54444 134801 29763200
Nasopharyngitis 140.11 34.13 322 54155 58527 29839474
Cardiac arrest 139.83 34.13 7 54470 92843 29805158
Migraine 139.30 34.13 143 54334 12731 29885270
Overdose 138.80 34.13 3 54474 84334 29813667
Memory impairment 138.33 34.13 245 54232 36929 29861072
Sepsis 138.19 34.13 47 54430 146348 29751653
Platelet count decreased 135.01 34.13 17 54460 106112 29791889
Enthesopathy 134.61 34.13 77 54400 2829 29895172
Completed suicide 133.98 34.13 13 54464 99479 29798522
Upper respiratory tract infection 130.34 34.13 202 54275 27274 29870727
Blood creatinine increased 122.87 34.13 12 54465 91363 29806638
Pleural effusion 120.46 34.13 3 54474 74063 29823938
Renal failure 118.95 34.13 43 54434 128923 29769078
Pruritus 116.36 34.13 474 54003 117730 29780271
Oedema peripheral 114.69 34.13 26 54451 105806 29792195
Fall 114.07 34.13 98 54379 181774 29716227
Product supply issue 110.21 34.13 34 54443 239 29897762
Discomfort 109.74 34.13 133 54344 14223 29883778
Pancytopenia 109.68 34.13 13 54464 85039 29812962
Pulmonary embolism 108.44 34.13 9 54468 78126 29819875
Seizure 107.09 34.13 24 54453 98451 29799550
Hyperkalaemia 102.58 34.13 4 54473 66006 29831995
Bradycardia 101.72 34.13 4 54473 65522 29832479
Arthritis 100.16 34.13 168 54309 24233 29873768
White blood cell count decreased 98.53 34.13 17 54460 83930 29814071
Tenosynovitis 96.84 34.13 67 54410 3448 29894553
Death 96.48 34.13 331 54146 356952 29541049
Deep vein thrombosis 96.34 34.13 3 54474 60498 29837503
Multiple organ dysfunction syndrome 94.88 34.13 5 54472 63482 29834519
Product use in unapproved indication 93.21 34.13 12 54465 73681 29824320
Gastrointestinal haemorrhage 91.40 34.13 20 54457 83426 29814575
Asthenia 89.09 34.13 167 54310 221123 29676878
Syncope 87.78 34.13 23 54454 84880 29813121
Unevaluable event 84.68 34.13 182 54295 31603 29866398
Tachycardia 84.23 34.13 16 54461 73723 29824278
Plasma cell myeloma 83.88 34.13 3 54474 53459 29844542
Interstitial lung disease 83.33 34.13 7 54470 60190 29837811
Insomnia 82.99 34.13 363 54114 92973 29805028
Disease progression 80.02 34.13 23 54454 79851 29818150
Septic shock 74.37 34.13 13 54464 63594 29834407
Dehydration 73.28 34.13 70 54407 123469 29774532
Hypokalaemia 71.83 34.13 5 54472 50187 29847814
Cardiac failure congestive 71.48 34.13 32 54445 84375 29813626
General physical health deterioration 70.03 34.13 48 54429 99896 29798105
Tongue disorder 69.83 34.13 60 54417 4262 29893739
Renal impairment 68.08 34.13 34 54443 84150 29813851
Neuropathy peripheral 67.51 34.13 22 54455 70453 29827548
Rhinorrhoea 67.35 34.13 129 54348 20625 29877376
Pain 67.25 34.13 540 53937 172101 29725900
Off label use 67.08 34.13 231 54246 249059 29648942
Mood swings 65.49 34.13 75 54402 7551 29890450
Sinus headache 64.69 34.13 33 54444 960 29897041
Loss of consciousness 64.27 34.13 32 54445 79343 29818658
C-reactive protein abnormal 63.91 34.13 64 54413 5529 29892472
Acute myocardial infarction 63.71 34.13 10 54467 52929 29845072
Hypoxia 62.45 34.13 7 54470 47847 29850154
Tendonitis 60.67 34.13 74 54403 7962 29890039
Atrial fibrillation 58.75 34.13 66 54411 108058 29789943
Cardiac failure 58.51 34.13 40 54437 83378 29814623
Infusion related reaction 58.16 34.13 4 54473 40560 29857441
Myocardial infarction 55.75 34.13 89 54388 125536 29772465
Drug intolerance 55.53 34.13 195 54282 45096 29852905
Hepatic function abnormal 55.08 34.13 6 54471 41939 29856062
Treatment failure 54.93 34.13 163 54314 34516 29863485
Alanine aminotransferase abnormal 54.20 34.13 42 54435 2577 29895424
Haematuria 52.76 34.13 9 54468 44825 29853176
Coronary artery disease 52.26 34.13 13 54464 49699 29848302
Synovitis 52.17 34.13 76 54401 9707 29888294
Arthropathy 52.14 34.13 116 54361 20611 29877390
Sinusitis 52.12 34.13 156 54321 33189 29864812
Loss of personal independence in daily activities 51.36 34.13 118 54359 21417 29876584
Leukopenia 51.25 34.13 19 54458 56140 29841861
Oedema 49.78 34.13 9 54468 42984 29855017
Decreased appetite 49.43 34.13 452 54025 149458 29748543
Pulmonary oedema 49.23 34.13 10 54467 43965 29854036
Feeling abnormal 49.07 34.13 219 54258 56537 29841464
Chest pain 48.81 34.13 87 54390 117540 29780461
Blood bilirubin increased 48.72 34.13 5 54472 36631 29861370
Coma 47.86 34.13 8 54469 40441 29857560
Therapy partial responder 47.34 34.13 45 54432 3646 29894355
Mental status changes 46.96 34.13 6 54471 37073 29860928
Blood alkaline phosphatase increased 45.45 34.13 3 54474 31484 29866517
Epistaxis 44.97 34.13 20 54457 52961 29845040
Dyspnoea exertional 44.23 34.13 6 54471 35424 29862577
Encephalopathy 43.87 34.13 4 54473 32201 29865800
Hyperglycaemia 43.85 34.13 6 54471 35194 29862807
Product use issue 42.95 34.13 15 54462 46001 29852000
Chills 42.84 34.13 41 54436 72297 29825704
Dysphagia 42.75 34.13 25 54452 56673 29841328
Stomatitis 42.74 34.13 8 54469 37271 29860730
Muscular weakness 42.68 34.13 32 54445 63613 29834388
Somnolence 42.49 34.13 69 54408 96694 29801307
Blood urea increased 42.47 34.13 4 54473 31377 29866624
Hallucination 42.46 34.13 18 54459 49041 29848960
Lactic acidosis 42.18 34.13 4 54473 31209 29866792
Gamma-glutamyltransferase increased 41.77 34.13 3 54474 29347 29868654
Jaundice 41.76 34.13 5 54472 32481 29865520
Chronic kidney disease 41.54 34.13 9 54468 37829 29860172
Weight increased 39.30 34.13 47 54430 74866 29823135
Bowel movement irregularity 38.74 34.13 33 54444 2316 29895685
Pneumonitis 38.52 34.13 3 54474 27451 29870550
Depressed mood 38.08 34.13 91 54386 16938 29881063
Influenza 37.91 34.13 168 54309 43230 29854771
Rash macular 36.83 34.13 67 54410 10300 29887701
Stress 36.80 34.13 100 54377 20135 29877866
Cerebral infarction 36.67 34.13 3 54474 26370 29871631
Acute respiratory failure 35.78 34.13 3 54474 25847 29872154
Intentional product use issue 35.55 34.13 11 54466 36429 29861572
Cerebrovascular accident 35.28 34.13 61 54416 83416 29814585
Muscle swelling 35.17 34.13 16 54461 359 29897642
Hepatocellular injury 35.13 34.13 3 54474 25468 29872533
Rash maculo-papular 35.04 34.13 3 54474 25415 29872586
Skin fissures 35.03 34.13 37 54440 3402 29894599
Liver function test abnormal 34.72 34.13 7 54470 30943 29867058
Anaphylactic reaction 34.31 34.13 5 54472 27977 29870024
Suicide attempt 34.18 34.13 12 54465 36685 29861316

Pharmacologic Action:

SourceCodeDescription
ATC L04AA32 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
MeSH PA D000700 Analgesics
MeSH PA D018712 Analgesics, Non-Narcotic
MeSH PA D000893 Anti-Inflammatory Agents
MeSH PA D000894 Anti-Inflammatory Agents, Non-Steroidal
MeSH PA D018501 Antirheumatic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D058988 Phosphodiesterase 4 Inhibitors
MeSH PA D010726 Phosphodiesterase Inhibitors
MeSH PA D018689 Sensory System Agents
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory drugs
CHEBI has role CHEBI:68844 pde4 inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Psoriasis with arthropathy indication 33339001
Plaque psoriasis indication 200965009
Beh├žet's disease affecting oral mucosa indication 403443000

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
10MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL July 19, 2022 TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
20MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL July 19, 2022 TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
30MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL July 19, 2022 TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
10MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL April 10, 2023 INFORMATION ADDED TO THE CLINICAL STUDIES SECTION OF THE LABELING REGARDING THE USE OF PLAQUE PSORIASIS OF THE SCALP
20MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL April 10, 2023 INFORMATION ADDED TO THE CLINICAL STUDIES SECTION OF THE LABELING REGARDING THE USE OF PLAQUE PSORIASIS OF THE SCALP
30MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL April 10, 2023 INFORMATION ADDED TO THE CLINICAL STUDIES SECTION OF THE LABELING REGARDING THE USE OF PLAQUE PSORIASIS OF THE SCALP
10MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL July 19, 2026 TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
20MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL July 19, 2026 TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
30MG OTEZLA AMGEN INC N205437 March 21, 2014 RX TABLET ORAL July 19, 2026 TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Enzyme INHIBITOR IC50 7.13 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme INHIBITOR IC50 7.85 IUPHAR
cAMP-specific 3',5'-cyclic phosphodiesterase 4C Enzyme INHIBITOR IC50 6.93 IUPHAR
cAMP-specific 3',5'-cyclic phosphodiesterase 4B Enzyme INHIBITOR IC50 7.57 IUPHAR

External reference:

IDSource
UP7QBP99PN UNII
D08860 KEGG_DRUG
4033216 VUID
N0000190644 NUI
4033216 VANDF
C1678805 UMLSCUI
CHEBI:78540 CHEBI
A9L PDB_CHEM_ID
CHEMBL514800 ChEMBL_ID
DB05676 DRUGBANK_ID
11561674 PUBCHEM_CID
8872 INN_ID
C505730 MESH_SUPPLEMENTAL_RECORD_UI
7372 IUPHAR_LIGAND_ID
1492727 RXNORM
213427 MMSL
30225 MMSL
d08247 MMSL
015411 NDDF
703350008 SNOMEDCT_US
714684002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Otezla HUMAN PRESCRIPTION DRUG LABEL 1 55513-137 TABLET, FILM COATED 30 mg ORAL NDA 29 sections
OTEZLA HUMAN PRESCRIPTION DRUG LABEL 1 59572-631 TABLET, FILM COATED 30 mg ORAL NDA 25 sections