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

Stem definitionDrug idCAS RN
guanylate cyclase activators and stimulators 4807 625115-55-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • adempas
  • BAY 63-2521
  • riociguat
guanylate cyclase stimulator
  • Molecular weight: 422.42
  • Formula: C20H19FN8O2
  • CLOGP: 1.84
  • LIPINSKI: 0
  • HAC: 10
  • HDO: 2
  • TPSA: 138.07
  • ALOGS: -3.79
  • ROTB: 5

  • Status: ONP

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

Drug dosage:

DoseUnitRoute
4.50 mg O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 0.44 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.74 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 9.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 8, 2013 FDA BAYER HLTHCARE

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
Dyspnoea 2557.19 46.39 812 2425 77921 2276927
Hospitalisation 2442.20 46.39 557 2680 14296 2340552
Headache 1834.85 46.39 640 2597 79539 2275309
Death 1634.10 46.39 591 2646 80877 2273971
Hypotension 1623.52 46.39 473 2764 31963 2322885
Dizziness 1590.22 46.39 534 2703 58131 2296717
Nausea 1421.67 46.39 583 2654 111606 2243242
Diarrhoea 1248.51 46.39 491 2746 83073 2271775
Fatigue 1155.89 46.39 467 2770 84406 2270442
Dyspnoea exertional 1149.09 46.39 255 2982 5465 2349383
Oedema peripheral 1043.35 46.39 315 2922 23448 2331400
Fluid retention 1027.17 46.39 242 2995 6804 2348044
Peripheral swelling 953.82 46.39 275 2962 17322 2337526
Dyspepsia 843.93 46.39 221 3016 9623 2345225
Vomiting 759.76 46.39 332 2905 71270 2283578
Cough 687.20 46.39 250 2987 32867 2321981
Oedema 634.02 46.39 178 3059 10025 2344823
Pulmonary arterial hypertension 632.94 46.39 148 3089 3962 2350886
Chest pain 599.92 46.39 217 3020 27920 2326928
Blood pressure decreased 586.66 46.39 164 3073 9072 2345776
Malaise 574.68 46.39 254 2983 55331 2299517
Pneumonia 553.82 46.39 239 2998 49057 2305791
Oxygen saturation decreased 542.86 46.39 148 3089 7438 2347410
Asthenia 508.62 46.39 222 3015 46704 2308144
Pain in jaw 482.23 46.39 130 3107 6242 2348606
Gastrooesophageal reflux disease 462.80 46.39 136 3101 8959 2345889
Epistaxis 427.17 46.39 130 3107 9649 2345199
Constipation 419.62 46.39 156 3081 21473 2333375
Weight increased 400.15 46.39 152 3085 22185 2332663
Product dose omission 397.30 46.39 176 3061 38081 2316767
Pain in extremity 388.83 46.39 179 3058 42361 2312487
Abdominal distension 377.25 46.39 120 3117 10291 2344557
Feeling abnormal 374.35 46.39 147 3090 23434 2331414
Pulmonary hypertension 370.87 46.39 101 3136 5017 2349831
Syncope 368.80 46.39 133 3104 16742 2338106
Blood pressure diastolic decreased 362.02 46.39 74 3163 1021 2353827
Abdominal discomfort 345.82 46.39 128 3109 17328 2337520
Decreased appetite 342.13 46.39 146 3091 28745 2326103
Palpitations 341.96 46.39 125 3112 16331 2338517
Fluid overload 327.75 46.39 81 3156 2725 2352123
Fall 308.65 46.39 158 3079 46941 2307907
Abdominal pain upper 302.70 46.39 124 3113 21976 2332872
Nasal congestion 296.90 46.39 91 3146 6875 2347973
Weight decreased 292.08 46.39 130 3107 28241 2326607
Nasopharyngitis 289.29 46.39 120 3117 21936 2332912
Pain 270.90 46.39 159 3078 61698 2293150
Swelling 269.77 46.39 105 3132 16245 2338603
Heart rate increased 251.44 46.39 90 3147 11015 2343833
Right ventricular failure 247.20 46.39 62 3175 2211 2352637
Flushing 241.86 46.39 89 3148 11782 2343066
Anaemia 239.86 46.39 121 3116 34671 2320177
Chest discomfort 213.53 46.39 86 3151 14509 2340339
Loss of consciousness 195.90 46.39 87 3150 18680 2336168
Joint swelling 195.12 46.39 84 3153 16735 2338113
Productive cough 195.03 46.39 62 3175 5259 2349589
Oxygen therapy 190.91 46.39 35 3202 258 2354590
Dehydration 190.77 46.39 90 3147 22205 2332643
Blood pressure systolic decreased 185.77 46.39 40 3197 715 2354133
Haemoglobin decreased 185.75 46.39 83 3154 18068 2336780
Back pain 180.36 46.39 97 3140 31562 2323286
Abdominal pain 175.61 46.39 98 3139 34276 2320572
Lung disorder 173.72 46.39 59 3178 6153 2348695
Dizziness postural 171.05 46.39 39 3198 915 2353933
Haemoptysis 166.85 46.39 50 3187 3477 2351371
Cardiac failure 165.57 46.39 68 3169 12026 2342822
Atrial fibrillation 160.36 46.39 69 3168 13699 2341149
Muscle spasms 160.03 46.39 79 3158 21487 2333361
Hypoxia 157.99 46.39 55 3182 6172 2348676
Arthralgia 153.09 46.39 106 3131 54179 2300669
Gastrointestinal disorder 152.89 46.39 59 3178 8858 2345990
Myalgia 151.23 46.39 78 3159 23255 2331593
Condition aggravated 149.28 46.39 86 3151 31893 2322955
Catheterisation cardiac 138.00 46.39 31 3206 678 2354170
Transfusion 130.23 46.39 36 3201 1872 2352976
Pulmonary endarterectomy 127.98 46.39 19 3218 25 2354823
Influenza 122.00 46.39 56 3181 12922 2341926
Ascites 121.14 46.39 44 3193 5576 2349272
Blood pressure abnormal 120.20 46.39 33 3204 1672 2353176
Cardiac failure congestive 119.36 46.39 59 3178 16042 2338806
Pulmonary thrombosis 118.55 46.39 30 3207 1104 2353744
Pulmonary arterial pressure increased 118.13 46.39 25 3212 409 2354439
Urinary tract infection 117.37 46.39 72 3165 29870 2324978
Gastrointestinal haemorrhage 114.81 46.39 53 3184 12382 2342466
Gastric disorder 110.59 46.39 37 3200 3673 2351175
Blood potassium decreased 108.63 46.39 40 3197 5265 2349583
Adverse drug reaction 107.93 46.39 45 3192 8238 2346610
Pyrexia 106.55 46.39 85 3152 53623 2301225
Insomnia 106.13 46.39 64 3173 25723 2329125
Intestinal obstruction 104.47 46.39 37 3200 4356 2350492
Pericardial effusion 103.90 46.39 36 3201 3973 2350875
Rales 103.89 46.39 27 3210 1106 2353742
Contusion 101.06 46.39 49 3188 12761 2342087
Drug intolerance 100.84 46.39 50 3187 13667 2341181
Respiratory failure 98.53 46.39 49 3188 13479 2341369
Unevaluable event 98.30 46.39 43 3194 8848 2346000
Bronchitis 94.95 46.39 48 3189 13666 2341182
Adverse event 94.38 46.39 40 3197 7619 2347229
Anxiety 93.60 46.39 62 3175 29297 2325551
Gait disturbance 92.85 46.39 56 3181 22489 2332359
Localised oedema 92.57 46.39 23 3214 784 2354064
Flatulence 92.19 46.39 34 3203 4491 2350357
Somnolence 90.74 46.39 56 3181 23429 2331419
Presyncope 90.30 46.39 32 3205 3771 2351077
Central venous catheterisation 90.27 46.39 20 3217 409 2354439
Product availability issue 90.07 46.39 17 3220 149 2354699
Renal failure 89.78 46.39 50 3187 17299 2337549
Infusion site pain 89.13 46.39 24 3213 1128 2353720
Product use issue 88.37 46.39 44 3193 12125 2342723
Clostridium difficile infection 86.82 46.39 29 3208 2861 2351987
Blood count abnormal 85.20 46.39 27 3210 2255 2352593
Renal disorder 85.12 46.39 32 3205 4456 2350392
Head injury 81.03 46.39 30 3207 4004 2350844
Chills 78.21 46.39 44 3193 15508 2339340
Diastolic hypotension 78.05 46.39 12 3225 23 2354825
Tachycardia 76.01 46.39 44 3193 16365 2338483
Retching 74.74 46.39 24 3213 2090 2352758
Chronic obstructive pulmonary disease 74.23 46.39 33 3204 7044 2347804
Sepsis 73.70 46.39 45 3192 18443 2336405
Rehabilitation therapy 73.63 46.39 16 3221 298 2354550
Oropharyngeal pain 72.99 46.39 38 3199 11480 2343368
Migraine 72.86 46.39 37 3200 10616 2344232
Catheter site erythema 72.03 46.39 18 3219 628 2354220
Respiratory tract congestion 72.01 46.39 24 3213 2350 2352498
Device related infection 71.99 46.39 26 3211 3233 2351615
Pleural effusion 69.69 46.39 37 3200 11631 2343217
Musculoskeletal pain 69.40 46.39 36 3201 10794 2344054
Tremor 69.11 46.39 45 3192 20616 2334232
General physical health deterioration 68.37 46.39 39 3198 14100 2340748
Balance disorder 67.08 46.39 34 3203 9713 2345135
Multiple allergies 66.61 46.39 18 3219 857 2353991
Blood pressure fluctuation 65.11 46.39 21 3216 1854 2352994
Cardiac disorder 64.86 46.39 31 3206 7802 2347046
Dyspnoea at rest 64.41 46.39 15 3222 386 2354462
Memory impairment 63.43 46.39 36 3201 12887 2341961
Limb injury 62.92 46.39 22 3215 2488 2352360
Intentional product use issue 62.23 46.39 24 3213 3578 2351270
Exercise tolerance decreased 62.07 46.39 16 3221 633 2354215
Pruritus 62.07 46.39 57 3180 43283 2311565
International normalised ratio increased 60.64 46.39 29 3208 7307 2347541
Pulmonary oedema 60.54 46.39 29 3208 7334 2347514
Sinusitis 60.21 46.39 38 3199 16488 2338360
Pulmonary congestion 60.13 46.39 20 3217 1945 2352903
Inappropriate schedule of product administration 59.90 46.39 34 3203 12170 2342678
Respiratory tract infection 59.62 46.39 24 3213 4005 2350843
Erythema 58.84 46.39 44 3193 25115 2329733
Oxygen consumption increased 58.81 46.39 14 3223 397 2354451
Surgery 58.64 46.39 26 3211 5509 2349339
Internal haemorrhage 57.98 46.39 15 3222 602 2354246
Gout 57.56 46.39 18 3219 1437 2353411
Rhinorrhoea 57.02 46.39 28 3209 7472 2347376
Haematochezia 56.51 46.39 25 3212 5270 2349578
Swelling face 56.38 46.39 30 3207 9463 2345385
Generalised oedema 56.19 46.39 20 3217 2383 2352465
Muscular weakness 56.14 46.39 35 3202 14862 2339986
Therapy change 54.11 46.39 16 3221 1057 2353791
Sinus disorder 54.07 46.39 20 3217 2658 2352190
Product supply issue 53.89 46.39 11 3226 149 2354699
Intentional product misuse 53.58 46.39 29 3208 9460 2345388
Neck pain 53.39 46.39 27 3210 7670 2347178
Choking 52.48 46.39 17 3220 1521 2353327
Catheter site infection 52.26 46.39 14 3223 644 2354204
Hospice care 52.18 46.39 14 3223 648 2354200
Wheezing 52.04 46.39 25 3212 6359 2348489
Seasonal allergy 51.51 46.39 17 3220 1613 2353235
Head discomfort 51.29 46.39 17 3220 1634 2353214
Rectal haemorrhage 50.99 46.39 24 3213 5832 2349016
Breath sounds abnormal 50.41 46.39 14 3223 738 2354110
Catheter site swelling 49.96 46.39 11 3226 218 2354630
Drug titration error 49.52 46.39 10 3227 128 2354720
Gallbladder disorder 49.37 46.39 19 3218 2815 2352033
Renal impairment 49.20 46.39 28 3209 10064 2344784
Vision blurred 49.14 46.39 32 3205 14636 2340212
Dysphonia 49.09 46.39 24 3213 6340 2348508
Catheter site pain 49.02 46.39 13 3224 575 2354273
Neuropathy peripheral 48.54 46.39 29 3208 11403 2343445
Vertigo 48.35 46.39 27 3210 9357 2345491
Sinus congestion 48.04 46.39 17 3220 1990 2352858
Catheter site haemorrhage 47.27 46.39 12 3225 446 2354402

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
Death 897.70 44.11 347 995 87096 1658343
Hospitalisation 831.79 44.11 211 1131 12489 1732950
Dyspnoea 725.45 44.11 261 1081 51798 1693641
Hypotension 469.13 44.11 165 1177 29489 1715950
Dizziness 464.14 44.11 170 1172 34191 1711248
Fluid retention 392.54 44.11 92 1250 3717 1741722
Headache 329.41 44.11 133 1209 34243 1711196
Dyspnoea exertional 317.77 44.11 79 1263 4082 1741357
Peripheral swelling 284.57 44.11 83 1259 7888 1737551
Oedema peripheral 284.13 44.11 97 1245 15453 1729986
Fatigue 282.55 44.11 134 1208 50647 1694792
Dyspepsia 260.37 44.11 70 1272 4915 1740524
Diarrhoea 236.06 44.11 121 1221 53731 1691708
Nausea 235.90 44.11 119 1223 51077 1694362
Oedema 228.59 44.11 68 1274 6880 1738559
Cough 184.86 44.11 75 1267 19122 1726317
Oxygen saturation decreased 184.09 44.11 55 1287 5620 1739819
Pulmonary hypertension 178.80 44.11 46 1296 2696 1742743
Fluid overload 171.43 44.11 42 1300 2013 1743426
Fall 162.79 44.11 76 1266 27138 1718301
Malaise 156.78 44.11 76 1266 29489 1715950
Syncope 152.25 44.11 60 1282 14109 1731330
Vomiting 152.23 44.11 81 1261 38234 1707205
Pneumonia 151.54 44.11 86 1256 46096 1699343
Blood pressure decreased 143.95 44.11 49 1293 7597 1737842
Abdominal distension 139.96 44.11 46 1296 6398 1739041
Weight increased 135.75 44.11 52 1290 11305 1734134
Constipation 135.18 44.11 56 1286 14944 1730495
Weight decreased 131.04 44.11 62 1280 22691 1722748
Asthenia 128.27 44.11 70 1272 34600 1710839
Pain in extremity 123.96 44.11 56 1286 18416 1727023
Haemoptysis 122.92 44.11 39 1303 4837 1740602
Epistaxis 120.99 44.11 44 1298 8262 1737177
Pulmonary arterial hypertension 105.42 44.11 27 1315 1543 1743896
Blood pressure diastolic decreased 103.00 44.11 23 1319 727 1744712
Chest pain 101.57 44.11 50 1292 19864 1725575
Decreased appetite 101.55 44.11 53 1289 23818 1721621
Product dose omission 98.81 44.11 51 1291 22389 1723050
Swelling 97.86 44.11 36 1306 6960 1738479
Nasal congestion 95.67 44.11 29 1313 3082 1742357
Pain in jaw 93.81 44.11 26 1316 2012 1743427
Gastrooesophageal reflux disease 92.09 44.11 31 1311 4616 1740823
Heart rate increased 89.19 44.11 33 1309 6477 1738962
Gastrointestinal disorder 87.51 44.11 30 1312 4718 1740721
Right ventricular failure 87.13 44.11 22 1320 1185 1744254
Surgery 85.08 44.11 26 1316 2837 1742602
Loss of consciousness 83.73 44.11 40 1302 14835 1730604
Abdominal discomfort 81.90 44.11 34 1308 9047 1736392
Oxygen therapy 79.15 44.11 14 1328 126 1745313
Joint swelling 78.98 44.11 30 1312 6323 1739116
Blood pressure systolic decreased 77.57 44.11 18 1324 676 1744763
Feeling abnormal 75.14 44.11 34 1308 11132 1734307
Ascites 71.66 44.11 27 1315 5559 1739880
Pulmonary endarterectomy 71.66 44.11 10 1332 12 1745427
Abdominal pain upper 66.18 44.11 31 1311 10970 1734469
Blood pressure abnormal 64.73 44.11 17 1325 1069 1744370
Lung disorder 62.96 44.11 24 1318 5095 1740344
Insomnia 57.43 44.11 32 1310 16244 1729195
Dyspnoea at rest 56.09 44.11 12 1330 308 1745131
Unevaluable event 55.60 44.11 23 1319 6043 1739396
Pain 54.57 44.11 37 1305 26620 1718819
Productive cough 52.05 44.11 19 1323 3572 1741867
Chest discomfort 51.40 44.11 23 1319 7308 1738131
Haemorrhage 50.88 44.11 25 1317 9804 1735635
Nasopharyngitis 50.45 44.11 25 1317 9985 1735454
Haematochezia 49.62 44.11 20 1322 4912 1740527
Dialysis 47.41 44.11 16 1326 2388 1743051
Transfusion 45.64 44.11 13 1329 1106 1744333
Dehydration 44.63 44.11 28 1314 17630 1727809

Pharmacologic Action:

SourceCodeDescription
ATC C02KX05 CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
OTHER ANTIHYPERTENSIVES
Antihypertensives for pulmonary arterial hypertension
CHEBI has role CHEBI:35674 antihypertensive agent
FDA MoA N0000190484 Guanylate Cyclase Stimulators
FDA EPC N0000190485 Soluble Guanylate Cyclase Stimulator
MeSH PA D020536 Enzyme Activators

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Pulmonary arterial hypertension indication 11399002
Chronic thromboembolic pulmonary hypertension indication 233947005
Pregnancy, function contraindication 289908002

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.68 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
0.5MG ADEMPAS BAYER HLTHCARE N204819 Oct. 8, 2013 RX TABLET ORAL Oct. 8, 2020 TREATMENT OF ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) WHO GROUP 1, TO IMPROVE EXERCISE CAPACITY, WHO FUNCTIONAL CLASS AND TO DELAY CLINICAL WORSENING.
1.5MG ADEMPAS BAYER HLTHCARE N204819 Oct. 8, 2013 RX TABLET ORAL Oct. 8, 2020 TREATMENT OF ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) WHO GROUP 1, TO IMPROVE EXERCISE CAPACITY, WHO FUNCTIONAL CLASS AND TO DELAY CLINICAL WORSENING.
1MG ADEMPAS BAYER HLTHCARE N204819 Oct. 8, 2013 RX TABLET ORAL Oct. 8, 2020 TREATMENT OF ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) WHO GROUP 1, TO IMPROVE EXERCISE CAPACITY, WHO FUNCTIONAL CLASS AND TO DELAY CLINICAL WORSENING.
2.5MG ADEMPAS BAYER HLTHCARE N204819 Oct. 8, 2013 RX TABLET ORAL Oct. 8, 2020 TREATMENT OF ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) WHO GROUP 1, TO IMPROVE EXERCISE CAPACITY, WHO FUNCTIONAL CLASS AND TO DELAY CLINICAL WORSENING.
2MG ADEMPAS BAYER HLTHCARE N204819 Oct. 8, 2013 RX TABLET ORAL Oct. 8, 2020 TREATMENT OF ADULTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) WHO GROUP 1, TO IMPROVE EXERCISE CAPACITY, WHO FUNCTIONAL CLASS AND TO DELAY CLINICAL WORSENING.

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Guanylate cyclase soluble subunit beta-1 Enzyme POSITIVE ALLOSTERIC MODULATOR MEC 7.52 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
cAMP-specific 3',5'-cyclic phosphodiesterase 7B Enzyme IC50 5.54 SCIENTIFIC LITERATURE

External reference:

IDSource
D09572 KEGG_DRUG
C3667657 UMLSCUI
715490004 SNOMEDCT_US
015236 NDDF
1439816 RXNORM
4032785 VANDF
29792 MMSL
d08140 MMSL
713333001 SNOMEDCT_US
11304743 PUBCHEM_CID
CHEBI:76018 CHEBI
RU3FE2Y4XI UNII
8857 INN_ID
DB08931 DRUGBANK_ID
CHEMBL2107834 ChEMBL_ID
5257 IUPHAR_LIGAND_ID
C542595 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Adempas HUMAN PRESCRIPTION DRUG LABEL 1 50419-250 TABLET, FILM COATED 0.50 mg ORAL NDA 18 sections
Adempas HUMAN PRESCRIPTION DRUG LABEL 1 50419-251 TABLET, FILM COATED 1 mg ORAL NDA 18 sections
Adempas HUMAN PRESCRIPTION DRUG LABEL 1 50419-252 TABLET, FILM COATED 1.50 mg ORAL NDA 18 sections
Adempas HUMAN PRESCRIPTION DRUG LABEL 1 50419-253 TABLET, FILM COATED 2 mg ORAL NDA 18 sections
Adempas HUMAN PRESCRIPTION DRUG LABEL 1 50419-254 TABLET, FILM COATED 2.50 mg ORAL NDA 18 sections