Identification

Name
Riociguat
Accession Number
DB08931
Type
Small Molecule
Groups
Approved
Description

Riociguat is a soluble guanylate cyclase (sGC) agonist approved in the USA, Europe and several other regions for patients with group I PAH (pulmonary arterial hypertension) in WHO FC II or III; and for the treatment of patients with inoperable CTEPH (chronic thromboembolic pulmonary hypertension), or persistent/recurrent PH (pulmonary hypertension) after pulmonary endarterectomy in WHO FC II or III. Riociguat is marketed under the brand Adempas® by Bayer HealthCare Pharmaceuticals. Treatment with riociguat costs USD $7,500 for 30 days of treatment.

Structure
Thumb
Synonyms
  • Methyl N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methyl-carbaminate
  • Riociguat
  • Riociguatum
External IDs
BAY 41-2272 / BAY 63-2521 / UNII-RU3FE2Y4XI
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AdempasTablet, film coated1.5 mgOralBayer Ag2014-03-27Not applicableEu
AdempasTablet, film coated1.5 mg/1OralBayer2013-10-08Not applicableUs
AdempasTablet, film coated1 mgOralBayer Ag2014-03-27Not applicableEu
AdempasTablet0.5 mgOralBayer2013-09-25Not applicableCanada
AdempasTablet, film coated1 mgOralBayer Ag2014-03-27Not applicableEu
AdempasTablet, film coated0.5 mgOralBayer Ag2014-03-27Not applicableEu
AdempasTablet, film coated2.5 mgOralBayer Ag2014-03-27Not applicableEu
AdempasTablet, film coated2 mgOralBayer Ag2014-03-27Not applicableEu
AdempasTablet, film coated2.5 mg/1OralBayer2013-10-08Not applicableUs
AdempasTablet, film coated2 mgOralBayer Ag2014-03-27Not applicableEu
Categories
UNII
RU3FE2Y4XI
CAS number
625115-55-1
Weight
Average: 422.4157
Monoisotopic: 422.161500097
Chemical Formula
C20H19FN8O2
InChI Key
WXXSNCNJFUAIDG-UHFFFAOYSA-N
InChI
InChI=1S/C20H19FN8O2/c1-28(20(30)31-2)15-16(22)25-18(26-17(15)23)14-12-7-5-9-24-19(12)29(27-14)10-11-6-3-4-8-13(11)21/h3-9H,10H2,1-2H3,(H4,22,23,25,26)
IUPAC Name
methyl N-(4,6-diamino-2-{1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}pyrimidin-5-yl)-N-methylcarbamate
SMILES
COC(=O)N(C)C1=C(N)N=C(N=C1N)C1=NN(CC2=C(F)C=CC=C2)C2=C1C=CC=N2

Pharmacology

Indication

Riociguat is indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), (WHO Group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class. Riociguat is indicated for the treatment of adults with pulmonary arterial hypertension (PAH), (WHO Group 1), to improve exercise capacity, WHO functional class and to delay clinical worsening. Efficacy was shown in patients on Riociguat monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominately patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%).

Structured Indications
Pharmacodynamics
Not Available
Mechanism of action

Riociguat is a stimulator of soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme catalyzes synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). Intracellular cGMP plays an important role in regulating processes that influence vascular tone, proliferation, fibrosis and inflammation. Pulmonary hypertension is associated with endothelial dysfunction, impaired synthesis of nitric oxide and insufficient stimulation of the NO-sGC-cGMP pathway.

Riociguat has a dual mode of action. It sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat stimulates the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation.

TargetActionsOrganism
AGuanylate cyclase soluble subunit alpha-2
agonist
stimulator
Human
Absorption

The pharmacokinetics of riociguant are dose proportional from 0.5 mg to 2.5 mg. The absolute bioavailability is approximately 94%. After oral administration, peak plasma concentrations were achieved within 1.5 hours. Food does not affect the bioavailability of riociguat.

Volume of distribution

Volume of distribution at steady state = 30 L

Protein binding

95% with serum albumin and alpha-1–acidic glycoprotein being the main binding components.

Metabolism

The active metabolite (M1) of riociguat is 1/3 to 1/10 as potent as riociguat.

Route of elimination

Riociguat is eliminated in the urine (40%) and feces (53%), largely as metabolites.

Half life

About 12 hours in patients and 7 hours in healthy subjects.

Clearance
Not Available
Toxicity

EMBRYO-FETAL TOXICITY Do not administer Riociguat to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception. For all female patients, Riociguat is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
1,10-PhenanthrolineThe serum concentration of Riociguat can be increased when it is combined with 1,10-Phenanthroline.Experimental
3,4-DichloroisocoumarinThe serum concentration of Riociguat can be increased when it is combined with 3,4-Dichloroisocoumarin.Experimental
4-(2-Aminoethyl)Benzenesulfonyl FluorideThe serum concentration of Riociguat can be increased when it is combined with 4-(2-Aminoethyl)Benzenesulfonyl Fluoride.Experimental
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Riociguat.Experimental
AbirateroneThe serum concentration of Riociguat can be increased when it is combined with Abiraterone.Approved
AcebutololAcebutolol may increase the hypotensive activities of Riociguat.Approved, Investigational
AcemetacinThe therapeutic efficacy of Riociguat can be decreased when used in combination with Acemetacin.Approved, Experimental, Investigational
Acetyl sulfisoxazoleThe metabolism of Riociguat can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Riociguat.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Riociguat.Approved, Investigational
AliskirenAliskiren may increase the hypotensive activities of Riociguat.Approved, Investigational
AlmasilateThe serum concentration of Riociguat can be decreased when it is combined with Almasilate.Approved, Experimental
AlogliptinThe serum concentration of Riociguat can be increased when it is combined with Alogliptin.Approved
AloglutamolThe serum concentration of Riociguat can be decreased when it is combined with Aloglutamol.Approved
Alpha-1-proteinase inhibitorThe serum concentration of Riociguat can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
AlprenololAlprenolol may increase the hypotensive activities of Riociguat.Approved, Withdrawn
AluminiumThe serum concentration of Riociguat can be decreased when it is combined with Aluminium.Approved, Investigational
Aluminium acetoacetateThe serum concentration of Riociguat can be decreased when it is combined with Aluminium acetoacetate.Experimental
Aluminium glycinateThe serum concentration of Riociguat can be decreased when it is combined with Aluminium glycinate.Experimental
Aluminum hydroxideThe serum concentration of Riociguat can be decreased when it is combined with Aluminum hydroxide.Approved, Investigational
AmbrisentanAmbrisentan may increase the hypotensive activities of Riociguat.Approved, Investigational
Ambroxol acefyllinateAmbroxol acefyllinate may increase the hypotensive activities of Riociguat.Experimental, Investigational
AmifostineRiociguat may increase the hypotensive activities of Amifostine.Approved, Investigational
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Riociguat.Approved
AminophyllineAminophylline may increase the hypotensive activities of Riociguat.Approved
AmiodaroneThe metabolism of Riociguat can be decreased when combined with Amiodarone.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Riociguat.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Riociguat.Approved, Illicit
AmphetamineAmphetamine may increase the hypotensive activities of Riociguat.Approved, Illicit, Investigational
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Riociguat.Approved, Investigational
AmprenavirThe serum concentration of Riociguat can be increased when it is combined with Amprenavir.Approved, Investigational
Amyl NitriteAmyl Nitrite may increase the hypotensive activities of Riociguat.Approved
AnagrelideAnagrelide may increase the hypotensive activities of Riociguat.Approved
Antithrombin III humanThe serum concentration of Riociguat can be increased when it is combined with Antithrombin III human.Approved
ApalutamideThe serum concentration of Riociguat can be decreased when it is combined with Apalutamide.Approved, Investigational
ApixabanThe serum concentration of Riociguat can be increased when it is combined with Apixaban.Approved
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Riociguat.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Apraclonidine is combined with Riociguat.Approved
ApremilastApremilast may increase the hypotensive activities of Riociguat.Approved, Investigational
AprepitantThe serum concentration of Riociguat can be increased when it is combined with Aprepitant.Approved, Investigational
AprotininThe serum concentration of Riociguat can be increased when it is combined with Aprotinin.Approved, Investigational, Withdrawn
ArgatrobanThe serum concentration of Riociguat can be increased when it is combined with Argatroban.Approved, Investigational
AripiprazoleAripiprazole may increase the hypotensive activities of Riociguat.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Riociguat.Investigational
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Riociguat.Approved, Investigational
AsunaprevirThe serum concentration of Riociguat can be increased when it is combined with Asunaprevir.Approved, Investigational, Withdrawn
AtazanavirThe serum concentration of Riociguat can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololAtenolol may increase the hypotensive activities of Riociguat.Approved
AtomoxetineThe metabolism of Riociguat can be decreased when combined with Atomoxetine.Approved
AvanafilAvanafil may increase the antihypertensive activities of Riociguat.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Riociguat.Approved, Investigational
BarbexacloneBarbexaclone may increase the hypotensive activities of Riociguat.Experimental
BarbitalBarbital may increase the hypotensive activities of Riociguat.Illicit
BarnidipineRiociguat may increase the antihypertensive activities of Barnidipine.Approved
BatimastatThe serum concentration of Riociguat can be increased when it is combined with Batimastat.Experimental
BenazeprilThe serum concentration of Riociguat can be increased when it is combined with Benazepril.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Riociguat.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Riociguat.Withdrawn
BenzamidineThe serum concentration of Riociguat can be increased when it is combined with Benzamidine.Experimental
BepridilBepridil may increase the hypotensive activities of Riociguat.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Riociguat.Approved, Investigational
BethanidineBethanidine may increase the hypotensive activities of Riociguat.Approved
BietaserpineBietaserpine may increase the hypotensive activities of Riociguat.Experimental
BimatoprostBimatoprost may increase the hypotensive activities of Riociguat.Approved, Investigational
Bismuth SubcitrateThe serum concentration of Riociguat can be decreased when it is combined with Bismuth Subcitrate.Approved, Investigational
Bismuth subnitrateThe serum concentration of Riociguat can be decreased when it is combined with Bismuth subnitrate.Approved
BisoprololBisoprolol may increase the hypotensive activities of Riociguat.Approved
BivalirudinThe serum concentration of Riociguat can be increased when it is combined with Bivalirudin.Approved, Investigational
BoceprevirThe serum concentration of Riociguat can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Riociguat can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Riociguat can be decreased when it is combined with Bosentan.Approved, Investigational
BQ-123BQ-123 may increase the hypotensive activities of Riociguat.Investigational
BretyliumBretylium may increase the hypotensive activities of Riociguat.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Riociguat.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Riociguat.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Riociguat.Approved, Investigational
BumetanideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Riociguat.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Riociguat.Approved, Investigational
BupranololBupranolol may increase the hypotensive activities of Riociguat.Approved
CadralazineCadralazine may increase the hypotensive activities of Riociguat.Experimental
CafedrineCafedrine may increase the hypotensive activities of Riociguat.Investigational
Calcium CarbonateThe serum concentration of Riociguat can be decreased when it is combined with Calcium Carbonate.Approved, Investigational
Calcium silicateThe serum concentration of Riociguat can be decreased when it is combined with Calcium silicate.Experimental
CamostatThe serum concentration of Riociguat can be increased when it is combined with Camostat.Experimental
CanagliflozinThe risk or severity of adverse effects can be increased when Canagliflozin is combined with Riociguat.Approved
CandesartanCandesartan may increase the hypotensive activities of Riociguat.Experimental
Candesartan cilexetilCandesartan cilexetil may increase the hypotensive activities of Riociguat.Approved
CandoxatrilThe serum concentration of Riociguat can be increased when it is combined with Candoxatril.Experimental
CandoxatrilatThe serum concentration of Riociguat can be increased when it is combined with Candoxatrilat.Experimental
CaptoprilThe serum concentration of Riociguat can be increased when it is combined with Captopril.Approved
CarbamazepineThe metabolism of Riociguat can be increased when combined with Carbamazepine.Approved, Investigational
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Riociguat.Approved, Investigational
CaroxazoneCaroxazone may increase the hypotensive activities of Riociguat.Withdrawn
CarteololCarteolol may increase the hypotensive activities of Riociguat.Approved
CarvedilolCarvedilol may increase the hypotensive activities of Riociguat.Approved, Investigational
CelecoxibThe metabolism of Riociguat can be decreased when combined with Celecoxib.Approved, Investigational
CeliprololCeliprolol may increase the hypotensive activities of Riociguat.Approved, Investigational
CeritinibThe serum concentration of Riociguat can be increased when it is combined with Ceritinib.Approved
ChlorothiazideChlorothiazide may increase the hypotensive activities of Riociguat.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Riociguat.Approved, Investigational, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Riociguat.Approved
CholesterolThe serum concentration of Riociguat can be increased when it is combined with Cholesterol.Approved, Investigational
ChymostatinThe serum concentration of Riociguat can be increased when it is combined with Chymostatin.Experimental
CicletanineCicletanine may increase the hypotensive activities of Riociguat.Investigational
CilastatinThe serum concentration of Riociguat can be increased when it is combined with Cilastatin.Approved, Investigational
CilazaprilThe serum concentration of Riociguat can be increased when it is combined with Cilazapril.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Riociguat.Approved, Investigational
CilostazolCilostazol may increase the hypotensive activities of Riociguat.Approved, Investigational
ClarithromycinThe metabolism of Riociguat can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Riociguat can be decreased when combined with Clemastine.Approved, Investigational
ClevidipineThe risk or severity of adverse effects can be increased when Clevidipine is combined with Riociguat.Approved, Investigational
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Riociguat.Approved, Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Riociguat.Approved, Investigational, Vet Approved
ClonidineClonidine may increase the hypotensive activities of Riociguat.Approved
CloranololCloranolol may increase the hypotensive activities of Riociguat.Experimental
ClotrimazoleThe metabolism of Riociguat can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Riociguat.Approved
CobicistatThe serum concentration of Riociguat can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Riociguat.Approved, Investigational
CrisaboroleThe metabolism of Riociguat can be decreased when combined with Crisaborole.Approved, Investigational
CrizotinibThe metabolism of Riociguat can be decreased when combined with Crizotinib.Approved
CryptenamineCryptenamine may increase the hypotensive activities of Riociguat.Approved
CyclopenthiazideCyclopenthiazide may increase the hypotensive activities of Riociguat.Experimental
CyclosporineThe metabolism of Riociguat can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclothiazideCyclothiazide may increase the hypotensive activities of Riociguat.Approved
Dabigatran etexilateThe serum concentration of Riociguat can be increased when it is combined with Dabigatran etexilate.Approved
DabrafenibThe serum concentration of Riociguat can be decreased when it is combined with Dabrafenib.Approved, Investigational
DapagliflozinThe risk or severity of adverse effects can be increased when Dapagliflozin is combined with Riociguat.Approved
DarexabanThe serum concentration of Riociguat can be increased when it is combined with Darexaban.Investigational
DarunavirThe serum concentration of Riociguat can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Riociguat can be increased when it is combined with Dasatinib.Approved, Investigational
DebrisoquinDebrisoquin may increase the hypotensive activities of Riociguat.Approved, Investigational
DeferasiroxThe serum concentration of Riociguat can be decreased when it is combined with Deferasirox.Approved, Investigational
DelanzomibThe serum concentration of Riociguat can be increased when it is combined with Delanzomib.Investigational
DelaprilThe serum concentration of Riociguat can be increased when it is combined with Delapril.Experimental
DelavirdineThe metabolism of Riociguat can be decreased when combined with Delavirdine.Approved
DeserpidineDeserpidine may increase the hypotensive activities of Riociguat.Approved
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Riociguat.Approved
DexlansoprazoleThe serum concentration of Riociguat can be decreased when it is combined with Dexlansoprazole.Approved, Investigational
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Riociguat.Approved, Vet Approved
DexrabeprazoleThe serum concentration of Riociguat can be decreased when it is combined with Dexrabeprazole.Experimental
DiazoxideDiazoxide may increase the hypotensive activities of Riociguat.Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Riociguat.Approved, Investigational
DiethylnorspermineDiethylnorspermine may increase the hypotensive activities of Riociguat.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Riociguat.Approved, Investigational
DihydroergotamineThe metabolism of Riociguat can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of Riociguat can be decreased when combined with Diltiazem.Approved, Investigational
DinutuximabThe risk or severity of adverse effects can be increased when Riociguat is combined with Dinutuximab.Approved, Investigational
DipyridamoleDipyridamole may increase the hypotensive activities of Riociguat.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Riociguat.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Riociguat.Approved
DoxofyllineDoxofylline may increase the hypotensive activities of Riociguat.Approved, Investigational
DoxycyclineThe metabolism of Riociguat can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Riociguat can be decreased when combined with Dronedarone.Approved
DuloxetineRiociguat may increase the orthostatic hypotensive activities of Duloxetine.Approved
DyphyllineDyphylline may increase the hypotensive activities of Riociguat.Approved
EcabetThe serum concentration of Riociguat can be increased when it is combined with Ecabet.Approved, Investigational
EdoxabanThe serum concentration of Riociguat can be increased when it is combined with Edoxaban.Approved
EfavirenzThe metabolism of Riociguat can be decreased when combined with Efavirenz.Approved, Investigational
EfonidipineEfonidipine may increase the hypotensive activities of Riociguat.Approved, Investigational
ElafinThe serum concentration of Riociguat can be increased when it is combined with Elafin.Investigational
EltrombopagThe serum concentration of Riociguat can be increased when it is combined with Eltrombopag.Approved
EmpagliflozinThe risk or severity of adverse effects can be increased when Riociguat is combined with Empagliflozin.Approved
EnalaprilThe serum concentration of Riociguat can be increased when it is combined with Enalapril.Approved, Vet Approved
EnalaprilatThe serum concentration of Riociguat can be increased when it is combined with Enalaprilat.Approved
EnalkirenThe serum concentration of Riociguat can be increased when it is combined with Enalkiren.Experimental
EndralazineEndralazine may increase the hypotensive activities of Riociguat.Experimental
EnzalutamideThe serum concentration of Riociguat can be decreased when it is combined with Enzalutamide.Approved
EpanololEpanolol may increase the hypotensive activities of Riociguat.Experimental
Epigallocatechin GallateThe serum concentration of Riociguat can be increased when it is combined with Epigallocatechin Gallate.Investigational
EplerenoneThe risk or severity of adverse effects can be increased when Eplerenone is combined with Riociguat.Approved
EpoprostenolEpoprostenol may increase the hypotensive activities of Riociguat.Approved
EprosartanEprosartan may increase the hypotensive activities of Riociguat.Approved
Erythrityl TetranitrateErythrityl Tetranitrate may increase the hypotensive activities of Riociguat.Approved, Investigational
ErythromycinThe metabolism of Riociguat can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EsmololThe risk or severity of adverse effects can be increased when Esmolol is combined with Riociguat.Approved
EsomeprazoleThe serum concentration of Riociguat can be decreased when it is combined with Esomeprazole.Approved, Investigational
Etacrynic acidThe risk or severity of adverse effects can be increased when Etacrynic acid is combined with Riociguat.Approved, Investigational
FaldaprevirThe serum concentration of Riociguat can be increased when it is combined with Faldaprevir.Investigational
FelodipineThe metabolism of Riociguat can be decreased when combined with Felodipine.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Riociguat.Approved
Ferulic acidFerulic acid may increase the hypotensive activities of Riociguat.Experimental
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Riociguat.Approved, Investigational
FluconazoleThe metabolism of Riociguat can be decreased when combined with Fluconazole.Approved, Investigational
FluvoxamineThe metabolism of Riociguat can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Riociguat can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Riociguat can be increased when it is combined with Fosaprepitant.Approved
FosinoprilThe serum concentration of Riociguat can be increased when it is combined with Fosinopril.Approved
FosphenytoinThe metabolism of Riociguat can be increased when combined with Fosphenytoin.Approved, Investigational
FurazolidoneFurazolidone may increase the hypotensive activities of Riociguat.Approved, Investigational, Vet Approved
FurosemideThe risk or severity of adverse effects can be increased when Furosemide is combined with Riociguat.Approved, Vet Approved
Fusidic AcidThe serum concentration of Riociguat can be increased when it is combined with Fusidic Acid.Approved, Investigational
GabexateThe serum concentration of Riociguat can be increased when it is combined with Gabexate.Investigational
GeldanamycinThe serum concentration of Riociguat can be increased when it is combined with Geldanamycin.Experimental, Investigational
GM6001The serum concentration of Riociguat can be increased when it is combined with GM6001.Experimental
GuanabenzGuanabenz may increase the hypotensive activities of Riociguat.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Riociguat.Approved
GuanazodineRiociguat may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineGuanethidine may increase the hypotensive activities of Riociguat.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Riociguat.Approved, Investigational
GuanoclorRiociguat may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzRiociguat may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanRiociguat may increase the hypotensive activities of Guanoxan.Experimental
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Riociguat.Approved, Vet Approved
HarmalineHarmaline may increase the hypotensive activities of Riociguat.Experimental
HexamethoniumHexamethonium may increase the hypotensive activities of Riociguat.Experimental
HexobarbitalHexobarbital may increase the hypotensive activities of Riociguat.Approved
HydracarbazineHydracarbazine may increase the hypotensive activities of Riociguat.Experimental
HydralazineHydralazine may increase the hypotensive activities of Riociguat.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Riociguat.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Riociguat.Approved, Investigational
HydrotalciteThe serum concentration of Riociguat can be decreased when it is combined with Hydrotalcite.Approved, Experimental, Investigational
IbudilastIbudilast may increase the hypotensive activities of Riociguat.Approved, Investigational
IdelalisibThe metabolism of Riociguat can be decreased when combined with Idelalisib.Approved
IdraparinuxThe serum concentration of Riociguat can be increased when it is combined with Idraparinux.Investigational
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with Riociguat.Approved, Investigational
ImatinibThe metabolism of Riociguat can be decreased when combined with Imatinib.Approved
ImidaprilThe serum concentration of Riociguat can be increased when it is combined with Imidapril.Investigational
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Riociguat.Approved
IndapamideIndapamide may increase the hypotensive activities of Riociguat.Approved
IndenololIndenolol may increase the hypotensive activities of Riociguat.Withdrawn
IndinavirThe serum concentration of Riociguat can be increased when it is combined with Indinavir.Approved
IndoraminIndoramin may increase the hypotensive activities of Riociguat.Withdrawn
IproclozideIproclozide may increase the hypotensive activities of Riociguat.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Riociguat.Withdrawn
IrbesartanThe metabolism of Riociguat can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoleThe serum concentration of Riociguat can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Riociguat can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Riociguat.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Riociguat.Approved, Vet Approved
IsoflurophateThe serum concentration of Riociguat can be increased when it is combined with Isoflurophate.Approved, Investigational, Withdrawn
Isosorbide DinitrateIsosorbide Dinitrate may increase the hypotensive activities of Riociguat.Approved, Investigational
Isosorbide MononitrateIsosorbide Mononitrate may increase the hypotensive activities of Riociguat.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Riociguat is combined with Isoxsuprine.Approved, Withdrawn
IsradipineThe metabolism of Riociguat can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe serum concentration of Riociguat can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Riociguat can be increased when it is combined with Ivacaftor.Approved
IxazomibThe serum concentration of Riociguat can be increased when it is combined with Ixazomib.Approved, Investigational
KetanserinKetanserin may increase the hypotensive activities of Riociguat.Investigational
KetoconazoleThe serum concentration of Riociguat can be increased when it is combined with Ketoconazole.Approved, Investigational
LabetalolLabetalol may increase the hypotensive activities of Riociguat.Approved
LacidipineRiociguat may increase the hypotensive activities of Lacidipine.Approved, Investigational
LansoprazoleThe serum concentration of Riociguat can be decreased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe metabolism of Riociguat can be decreased when combined with Lapatinib.Approved, Investigational
LatanoprostLatanoprost may increase the hypotensive activities of Riociguat.Approved, Investigational
LepirudinThe serum concentration of Riociguat can be increased when it is combined with Lepirudin.Approved
LercanidipineLercanidipine may increase the hypotensive activities of Riociguat.Approved, Investigational
LetaxabanThe serum concentration of Riociguat can be increased when it is combined with Letaxaban.Investigational
LevobunololThe risk or severity of adverse effects can be increased when Levobunolol is combined with Riociguat.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Riociguat.Approved, Investigational
LevodopaRiociguat may increase the orthostatic hypotensive activities of Levodopa.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Levosimendan is combined with Riociguat.Approved, Investigational
LinagliptinThe serum concentration of Riociguat can be increased when it is combined with Linagliptin.Approved
LinsidomineLinsidomine may increase the hypotensive activities of Riociguat.Experimental
LisinoprilThe serum concentration of Riociguat can be increased when it is combined with Lisinopril.Approved, Investigational
LofexidineLofexidine may increase the hypotensive activities of Riociguat.Approved, Investigational
LopinavirThe serum concentration of Riociguat can be increased when it is combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Riociguat can be increased when it is combined with Lorpiprazole.Approved
LosartanThe metabolism of Riociguat can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Riociguat can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Riociguat can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Riociguat can be increased when it is combined with Lumacaftor.Approved
MacitentanRiociguat may increase the hypotensive activities of Macitentan.Approved
MagaldrateThe serum concentration of Riociguat can be decreased when it is combined with Magaldrate.Approved, Withdrawn
Magnesium hydroxideThe serum concentration of Riociguat can be decreased when it is combined with Magnesium hydroxide.Approved, Investigational
Magnesium oxideThe serum concentration of Riociguat can be decreased when it is combined with Magnesium oxide.Approved
Magnesium peroxideThe serum concentration of Riociguat can be decreased when it is combined with Magnesium peroxide.Experimental
Magnesium silicateThe serum concentration of Riociguat can be decreased when it is combined with Magnesium silicate.Approved
Magnesium TrisilicateThe serum concentration of Riociguat can be decreased when it is combined with Magnesium Trisilicate.Approved
ManidipineManidipine may increase the hypotensive activities of Riociguat.Approved, Investigational
MannitolThe risk or severity of adverse effects can be increased when Mannitol is combined with Riociguat.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Riociguat.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Riociguat.Approved, Investigational
MelagatranThe serum concentration of Riociguat can be increased when it is combined with Melagatran.Experimental
MethazolamideThe risk or severity of adverse effects can be increased when Methazolamide is combined with Riociguat.Approved
MethohexitalMethohexital may increase the hypotensive activities of Riociguat.Approved
MethoserpidineRiociguat may increase the hypotensive activities of Methoserpidine.Experimental
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Riociguat.Approved
MethyldopaMethyldopa may increase the hypotensive activities of Riociguat.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Riociguat.Approved, Investigational
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Riociguat.Approved, Investigational
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Riociguat.Approved
Methylpropylpropanediol dinitrateMethylpropylpropanediol dinitrate may increase the hypotensive activities of Riociguat.Experimental
MetipranololMetipranolol may increase the hypotensive activities of Riociguat.Approved
MetolazoneMetolazone may increase the hypotensive activities of Riociguat.Approved
MetoprololMetoprolol may increase the hypotensive activities of Riociguat.Approved, Investigational
MetyrosineMetyrosine may increase the hypotensive activities of Riociguat.Approved
MibefradilMibefradil may increase the hypotensive activities of Riociguat.Investigational, Withdrawn
MifepristoneThe serum concentration of Riociguat can be increased when it is combined with Mifepristone.Approved, Investigational
MilrinoneMilrinone may increase the hypotensive activities of Riociguat.Approved
MinaprineMinaprine may increase the hypotensive activities of Riociguat.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Riociguat.Approved, Investigational
MirodenafilMirodenafil may increase the antihypertensive activities of Riociguat.Investigational
MitotaneThe serum concentration of Riociguat can be decreased when it is combined with Mitotane.Approved
MoclobemideMoclobemide may increase the hypotensive activities of Riociguat.Approved, Investigational
MoexiprilThe serum concentration of Riociguat can be increased when it is combined with Moexipril.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Riociguat.Approved, Investigational
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Riociguat.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Riociguat.Approved, Investigational
MuzolimineMuzolimine may increase the hypotensive activities of Riociguat.Experimental
N-(3-Propylcarbamoyloxirane-2-Carbonyl)-Isoleucyl-ProlineThe serum concentration of Riociguat can be increased when it is combined with N-(3-Propylcarbamoyloxirane-2-Carbonyl)-Isoleucyl-Proline.Experimental
NabiloneThe risk or severity of adverse effects can be increased when Nabilone is combined with Riociguat.Approved, Investigational
NadololNadolol may increase the hypotensive activities of Riociguat.Approved
NafamostatThe serum concentration of Riociguat can be increased when it is combined with Nafamostat.Approved, Investigational
NaftopidilNaftopidil may increase the hypotensive activities of Riociguat.Investigational
NebivololNebivolol may increase the hypotensive activities of Riociguat.Approved, Investigational
NefazodoneThe metabolism of Riociguat can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Riociguat can be increased when it is combined with Nelfinavir.Approved
NesiritideThe risk or severity of adverse effects can be increased when Nesiritide is combined with Riociguat.Approved, Investigational
NetupitantThe serum concentration of Riociguat can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Riociguat can be increased when combined with Nevirapine.Approved
NialamideNialamide may increase the hypotensive activities of Riociguat.Withdrawn
NicardipineNicardipine may increase the hypotensive activities of Riociguat.Approved, Investigational
NicorandilNicorandil may increase the hypotensive activities of Riociguat.Approved, Investigational
NifedipineThe risk or severity of adverse effects can be increased when Nifedipine is combined with Riociguat.Approved
NiguldipineNiguldipine may increase the hypotensive activities of Riociguat.Experimental
NilotinibThe metabolism of Riociguat can be decreased when combined with Nilotinib.Approved, Investigational
NilvadipineNilvadipine may increase the hypotensive activities of Riociguat.Approved, Investigational
NimodipineNimodipine may increase the hypotensive activities of Riociguat.Approved, Investigational
NisoldipineNisoldipine may increase the hypotensive activities of Riociguat.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Riociguat.Approved, Investigational
Nitric OxideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Riociguat.Approved
NitroaspirinThe serum concentration of Riociguat can be increased when it is combined with Nitroaspirin.Investigational
NitroglycerinNitroglycerin may increase the hypotensive activities of Riociguat.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Riociguat.Approved, Investigational
Nitrous acidThe risk or severity of adverse effects can be increased when Nitrous acid is combined with Riociguat.Approved, Investigational
ObinutuzumabRiociguat may increase the hypotensive activities of Obinutuzumab.Approved, Investigational
OctamoxinOctamoxin may increase the hypotensive activities of Riociguat.Withdrawn
OlaparibThe metabolism of Riociguat can be decreased when combined with Olaparib.Approved
OlmesartanOlmesartan may increase the hypotensive activities of Riociguat.Approved, Investigational
OmapatrilatThe serum concentration of Riociguat can be increased when it is combined with Omapatrilat.Investigational
OmeprazoleThe serum concentration of Riociguat can be decreased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Riociguat can be increased when it is combined with Osimertinib.Approved
OtamixabanThe serum concentration of Riociguat can be increased when it is combined with Otamixaban.Investigational
OxprenololOxprenolol may increase the hypotensive activities of Riociguat.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Riociguat.Approved, Vet Approved
PalbociclibThe serum concentration of Riociguat can be increased when it is combined with Palbociclib.Approved, Investigational
PantoprazoleThe serum concentration of Riociguat can be decreased when it is combined with Pantoprazole.Approved
PapaverineThe risk or severity of adverse effects can be increased when Papaverine is combined with Riociguat.Approved, Investigational
PargylinePargyline may increase the hypotensive activities of Riociguat.Approved
Patent BlueThe therapeutic efficacy of Riociguat can be decreased when used in combination with Patent Blue.Approved
PenbutololPenbutolol may increase the hypotensive activities of Riociguat.Approved, Investigational
Pentaerythritol TetranitratePentaerythritol Tetranitrate may increase the hypotensive activities of Riociguat.Approved
PentobarbitalThe metabolism of Riociguat can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PentoliniumPentolinium may increase the hypotensive activities of Riociguat.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Riociguat.Approved, Investigational
PerindoprilThe serum concentration of Riociguat can be increased when it is combined with Perindopril.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Riociguat.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Riociguat.Withdrawn
PhenobarbitalThe metabolism of Riociguat can be increased when combined with Phenobarbital.Approved, Investigational
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Riociguat.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Riociguat.Withdrawn
PhentolaminePhentolamine may increase the hypotensive activities of Riociguat.Approved
PhenytoinThe metabolism of Riociguat can be increased when combined with Phenytoin.Approved, Vet Approved
PhosphoramidonThe serum concentration of Riociguat can be increased when it is combined with Phosphoramidon.Experimental
PinacidilPinacidil may increase the hypotensive activities of Riociguat.Approved
PindololPindolol may increase the hypotensive activities of Riociguat.Approved, Investigational
PioglitazoneThe metabolism of Riociguat can be decreased when combined with Pioglitazone.Approved, Investigational
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Riociguat.Approved, Investigational
PirlindolePirlindole may increase the hypotensive activities of Riociguat.Approved
PitolisantThe serum concentration of Riociguat can be decreased when it is combined with Pitolisant.Approved, Investigational
PivhydrazinePivhydrazine may increase the hypotensive activities of Riociguat.Withdrawn
Platelet Activating FactorPlatelet Activating Factor may increase the hypotensive activities of Riociguat.Experimental
PolythiazidePolythiazide may increase the hypotensive activities of Riociguat.Approved
PosaconazoleThe metabolism of Riociguat can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PramipexoleThe risk or severity of adverse effects can be increased when Pramipexole is combined with Riociguat.Approved, Investigational
PrazosinPrazosin may increase the hypotensive activities of Riociguat.Approved
PrimidoneThe metabolism of Riociguat can be increased when combined with Primidone.Approved, Vet Approved
PrinomastatThe serum concentration of Riociguat can be increased when it is combined with Prinomastat.Investigational
ProcarbazineProcarbazine may increase the hypotensive activities of Riociguat.Approved, Investigational
Propatyl nitratePropatyl nitrate may increase the hypotensive activities of Riociguat.Experimental, Investigational
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Riociguat.Approved, Investigational, Vet Approved
PropranololPropranolol may increase the hypotensive activities of Riociguat.Approved, Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Riociguat.Approved
QuinaprilThe serum concentration of Riociguat can be increased when it is combined with Quinapril.Approved, Investigational
QuinineThe metabolism of Riociguat can be decreased when combined with Quinine.Approved
RabeprazoleThe serum concentration of Riociguat can be decreased when it is combined with Rabeprazole.Approved, Investigational
RacecadotrilThe serum concentration of Riociguat can be increased when it is combined with Racecadotril.Investigational
RamiprilThe serum concentration of Riociguat can be increased when it is combined with Ramipril.Approved
RanolazineThe metabolism of Riociguat can be decreased when combined with Ranolazine.Approved, Investigational
RasagilineRasagiline may increase the hypotensive activities of Riociguat.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Riociguat.Approved
RemikirenThe serum concentration of Riociguat can be increased when it is combined with Remikiren.Approved
RescinnamineRescinnamine may increase the hypotensive activities of Riociguat.Approved
ReserpineReserpine may increase the hypotensive activities of Riociguat.Approved, Investigational
RifabutinThe metabolism of Riociguat can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Riociguat can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Riociguat can be increased when combined with Rifapentine.Approved, Investigational
RilmenidineRilmenidine may increase the hypotensive activities of Riociguat.Approved, Investigational
RisperidoneRiociguat may increase the hypotensive activities of Risperidone.Approved, Investigational
RitonavirThe serum concentration of Riociguat can be increased when it is combined with Ritonavir.Approved, Investigational
RituximabRiociguat may increase the hypotensive activities of Rituximab.Approved
RivaroxabanThe serum concentration of Riociguat can be increased when it is combined with Rivaroxaban.Approved
RoflumilastRoflumilast may increase the hypotensive activities of Riociguat.Approved
RolapitantThe serum concentration of Riociguat can be increased when it is combined with Rolapitant.Approved, Investigational
RopiniroleThe risk or severity of adverse effects can be increased when Ropinirole is combined with Riociguat.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Riociguat.Approved
RosiglitazoneThe metabolism of Riociguat can be decreased when combined with Rosiglitazone.Approved, Investigational
RotigotineThe risk or severity of adverse effects can be increased when Rotigotine is combined with Riociguat.Approved
RucaparibThe metabolism of Riociguat can be decreased when combined with Rucaparib.Approved, Investigational
S-3304The serum concentration of Riociguat can be increased when it is combined with S-3304.Investigational
SacubitrilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Riociguat.Approved
SafrazineSafrazine may increase the hypotensive activities of Riociguat.Withdrawn
SaprisartanSaprisartan may increase the hypotensive activities of Riociguat.Experimental
SaquinavirThe serum concentration of Riociguat can be increased when it is combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Riociguat can be decreased when used in combination with Sarilumab.Approved, Investigational
SaxagliptinThe serum concentration of Riociguat can be increased when it is combined with Saxagliptin.Approved
SecobarbitalThe metabolism of Riociguat can be increased when combined with Secobarbital.Approved, Vet Approved
SelegilineSelegiline may increase the hypotensive activities of Riociguat.Approved, Investigational, Vet Approved
SelexipagSelexipag may increase the hypotensive activities of Riociguat.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Sevoflurane is combined with Riociguat.Approved, Vet Approved
SildenafilSildenafil may increase the hypotensive activities of Riociguat.Approved, Investigational
SiltuximabThe serum concentration of Riociguat can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Riociguat can be increased when it is combined with Simeprevir.Approved
SitagliptinThe serum concentration of Riociguat can be increased when it is combined with Sitagliptin.Approved, Investigational
SitaxentanSitaxentan may increase the hypotensive activities of Riociguat.Approved, Investigational, Withdrawn
SivelestatThe serum concentration of Riociguat can be increased when it is combined with Sivelestat.Investigational
Sodium bicarbonateThe serum concentration of Riociguat can be decreased when it is combined with Sodium bicarbonate.Approved
SotalolThe risk or severity of adverse effects can be increased when Sotalol is combined with Riociguat.Approved
SpiraprilThe serum concentration of Riociguat can be increased when it is combined with Spirapril.Approved
SpironolactoneThe risk or severity of adverse effects can be increased when Spironolactone is combined with Riociguat.Approved
St. John's WortThe serum concentration of Riociguat can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Riociguat can be increased when it is combined with Stiripentol.Approved
StreptokinaseThe risk or severity of adverse effects can be increased when Streptokinase is combined with Riociguat.Approved, Investigational
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Riociguat.Approved, Investigational
SulfamethoxazoleThe metabolism of Riociguat can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Riociguat can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TadalafilTadalafil may increase the hypotensive activities of Riociguat.Approved, Investigational
TalinololTalinolol may increase the hypotensive activities of Riociguat.Investigational
TamoxifenThe metabolism of Riociguat can be decreased when combined with Tamoxifen.Approved
TamsulosinThe risk or severity of adverse effects can be increased when Tamsulosin is combined with Riociguat.Approved, Investigational
TelaprevirThe serum concentration of Riociguat can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Riociguat can be decreased when combined with Telithromycin.Approved
TelmisartanTelmisartan may increase the hypotensive activities of Riociguat.Approved, Investigational
TemocaprilThe serum concentration of Riociguat can be increased when it is combined with Temocapril.Experimental, Investigational
TenitramineTenitramine may increase the hypotensive activities of Riociguat.Experimental
TerazosinThe risk or severity of adverse effects can be increased when Terazosin is combined with Riociguat.Approved
TeriflunomideThe serum concentration of Riociguat can be increased when it is combined with Teriflunomide.Approved
TerlipressinTerlipressin may increase the hypotensive activities of Riociguat.Approved, Investigational
TetrahydropalmatineTetrahydropalmatine may increase the hypotensive activities of Riociguat.Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Riociguat.Approved, Investigational, Withdrawn
TheodrenalineTheodrenaline may increase the hypotensive activities of Riociguat.Investigational
TheophyllineTheophylline may increase the hypotensive activities of Riociguat.Approved
ThiamylalThiamylal may increase the hypotensive activities of Riociguat.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Riociguat.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Thioridazine is combined with Riociguat.Approved, Withdrawn
ThiorphanThe serum concentration of Riociguat can be increased when it is combined with Thiorphan.Experimental
TiboloneTibolone may increase the hypotensive activities of Riociguat.Approved, Investigational
TiclopidineThe metabolism of Riociguat can be decreased when combined with Ticlopidine.Approved
TicrynafenTicrynafen may increase the hypotensive activities of Riociguat.Withdrawn
TimololTimolol may increase the hypotensive activities of Riociguat.Approved
TipranavirThe serum concentration of Riociguat can be increased when it is combined with Tipranavir.Approved, Investigational
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Riociguat.Approved, Investigational
TocilizumabThe serum concentration of Riociguat can be decreased when it is combined with Tocilizumab.Approved
TolazolineTolazoline may increase the hypotensive activities of Riociguat.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Riociguat.Approved, Withdrawn
TolonidineRiociguat may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneToloxatone may increase the hypotensive activities of Riociguat.Approved
TopiroxostatThe metabolism of Riociguat can be decreased when combined with Topiroxostat.Approved, Investigational
TorasemideTorasemide may increase the hypotensive activities of Riociguat.Approved
TrandolaprilThe serum concentration of Riociguat can be increased when it is combined with Trandolapril.Approved
TranylcypromineTranylcypromine may increase the hypotensive activities of Riociguat.Approved, Investigational
TravoprostTravoprost may increase the hypotensive activities of Riociguat.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Riociguat.Approved, Investigational
TretinoinThe risk or severity of adverse effects can be increased when Tretinoin is combined with Riociguat.Approved, Investigational, Nutraceutical
TriamtereneThe risk or severity of adverse effects can be increased when Triamterene is combined with Riociguat.Approved
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Riociguat.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Riociguat.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Riociguat.Approved, Investigational
TrimethoprimThe metabolism of Riociguat can be decreased when combined with Trimethoprim.Approved, Vet Approved
TrolnitrateTrolnitrate may increase the hypotensive activities of Riociguat.Experimental
TromethamineThe serum concentration of Riociguat can be decreased when it is combined with Tromethamine.Approved
UbenimexThe serum concentration of Riociguat can be increased when it is combined with Ubenimex.Experimental, Investigational
UdenafilUdenafil may increase the antihypertensive activities of Riociguat.Approved, Investigational
UlinastatinThe serum concentration of Riociguat can be increased when it is combined with Ulinastatin.Investigational
UnoprostoneUnoprostone may increase the hypotensive activities of Riociguat.Approved, Investigational
UrapidilUrapidil may increase the hypotensive activities of Riociguat.Investigational
ValsartanValsartan may increase the hypotensive activities of Riociguat.Approved, Investigational
VardenafilVardenafil may increase the hypotensive activities of Riociguat.Approved
VemurafenibThe serum concentration of Riociguat can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Riociguat can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Riociguat can be decreased when combined with Verapamil.Approved
VildagliptinThe serum concentration of Riociguat can be increased when it is combined with Vildagliptin.Approved, Investigational
VincamineVincamine may increase the hypotensive activities of Riociguat.Experimental
VinpocetineVinpocetine may increase the hypotensive activities of Riociguat.Investigational
VoriconazoleThe metabolism of Riociguat can be decreased when combined with Voriconazole.Approved, Investigational
XimelagatranThe serum concentration of Riociguat can be increased when it is combined with Ximelagatran.Approved, Investigational, Withdrawn
XipamideXipamide may increase the hypotensive activities of Riociguat.Experimental
XylometazolineXylometazoline may increase the hypotensive activities of Riociguat.Approved, Investigational
YohimbineYohimbine may decrease the antihypertensive activities of Riociguat.Approved, Investigational, Vet Approved
Z-Val-Ala-Asp fluoromethyl ketoneThe serum concentration of Riociguat can be increased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental
ZiprasidoneThe metabolism of Riociguat can be decreased when combined with Ziprasidone.Approved
ZofenoprilThe serum concentration of Riociguat can be increased when it is combined with Zofenopril.Experimental
Food Interactions
Not Available

References

Synthesis Reference

"Patent Link":http://www.google.com/patents/US7173037

General References
  1. Soeiro-Pereira PV, Falcai A, Kubo CA, Oliveira-Junior EB, Marques OC, Antunes E, Condino-Neto A: BAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes. Br J Pharmacol. 2012 Jul;166(5):1617-30. doi: 10.1111/j.1476-5381.2011.01764.x. [PubMed:22044316]
  2. Hambly N, Granton J: Riociguat for the treatment of pulmonary hypertension. Expert Rev Respir Med. 2015;9(6):679-95. doi: 10.1586/17476348.2015.1106316. Epub 2015 Nov 24. [PubMed:26599488]
  3. Humbert M, Ghofrani HA: The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax. 2016 Jan;71(1):73-83. doi: 10.1136/thoraxjnl-2015-207170. Epub 2015 Jul 28. [PubMed:26219978]
  4. Conole D, Scott LJ: Riociguat: first global approval. Drugs. 2013 Nov;73(17):1967-75. doi: 10.1007/s40265-013-0149-5. [PubMed:24218053]
  5. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]
External Links
KEGG Drug
D09572
PubChem Compound
11304743
PubChem Substance
310264904
ChemSpider
9479719
ChEBI
76018
ChEMBL
CHEMBL2107834
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Riociguat
ATC Codes
C02KX05 — Riociguat
AHFS Codes
  • 48:48.00 — Vasodilating Agents
FDA label
Download (1.55 MB)
MSDS
Download (246 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableDrug Interactions1
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailablePharmacology, Clinical1
1CompletedOtherHIV-DDI1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentPharmacology, Clinical1
1CompletedTreatmentPulmonary Disease, Chronic Obstructive / Pulmonary Hypertension (PH)1
1CompletedTreatmentPulmonary Hypertension (PH)1
2Active Not RecruitingTreatmentPulmonary Hypertension (PH)1
2Active Not RecruitingTreatmentPulmonary Hypertension (PH) / Ventricular Dysfunction, Left1
2Active Not RecruitingTreatmentScleroderma, Systemic1
2CompletedNot AvailableRaynaud's Disease1
2CompletedTreatmentPulmonary Hypertension (PH)2
2Not Yet RecruitingTreatmentChronic Thromboembolic Disease (CTED) / Exercise Intolerance Post PEA Surgery1
2Not Yet RecruitingTreatmentChronic Thromboembolic Pulmonary Hypertension1
2RecruitingTreatmentDigital Ulcers / Scleroderma1
2RecruitingTreatmentHeart Failure With Normal Ejection Fraction / Pulmonary Hypertension (PH)1
2RecruitingTreatmentSickle Cell Disorders1
2TerminatedTreatmentCystic Fibrosis (CF)1
2TerminatedTreatmentIdiopathic Interstitial Pneumonias / Hypertension,Pulmonary1
2TerminatedTreatmentPulmonary Hypertension (PH) / Ventricular Dysfunction, Left2
2WithdrawnTreatmentCoronary Artery Disease1
3Active Not RecruitingTreatmentPulmonary Hypertension (PH)2
3CompletedTreatmentPulmonary Hypertension (PH)3
3RecruitingTreatmentPulmonary Hypertension (PH)1
4CompletedNot AvailableAltitude Sickness / Pulmonary Hypertension (PH)1
4CompletedTreatmentPulmonary / Pulmonary Hypertension (PH)1
4RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
4RecruitingTreatmentPulmonary Hypertension (PH)1
4RecruitingTreatmentSarcoidosis1
Not AvailableActive Not RecruitingNot AvailablePulmonary Hypertension (PH)1
Not AvailableCompletedNot AvailablePulmonary Hypertension (PH)1
Not AvailableNo Longer AvailableNot AvailablePulmonary Hypertension (PH)1
Not AvailableRecruitingNot AvailablePulmonary Hypertension (PH)2
Not AvailableRecruitingDiagnosticChronic Thromboembolic Pulmonary Hypertension / Sleep Disordered Breathing (SDB)1
Not AvailableRecruitingTreatmentChronic Thromboembolic Pulmonary Hypertension1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral0.5 mg
TabletOral1 mg
TabletOral1.5 mg
TabletOral2 mg
TabletOral2.5 mg
Tablet, film coatedOral.5 mg/1
Tablet, film coatedOral0.5 mg
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral1 mg
Tablet, film coatedOral1.5 mg/1
Tablet, film coatedOral1.5 mg
Tablet, film coatedOral2 mg/1
Tablet, film coatedOral2 mg
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral2.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7173037No2003-04-252023-04-25Us
US6743798No1999-07-162019-07-16Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility4 mg/L at 25°CFDA label
Predicted Properties
PropertyValueSource
Water Solubility0.0682 mg/mLALOGPS
logP2.27ALOGPS
logP2.69ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)18.9ChemAxon
pKa (Strongest Basic)3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area138.07 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity135.25 m3·mol-1ChemAxon
Polarizability41.9 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrazolopyridines. These are compounds containing a pyrazolopyridine skeleton, which consists of a pyrazole fused to a pyridine. Pyrazole is 5-membered ring consisting of three carbon atoms and two adjacent nitrogen centers. Pyridine is a 6-membered ring with four carbon and one nitrogen atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrazolopyridines
Sub Class
Not Available
Direct Parent
Pyrazolopyridines
Alternative Parents
Aminopyrimidines and derivatives / Fluorobenzenes / Pyridines and derivatives / Aryl fluorides / Imidolactams / Pyrazoles / Carbamate esters / Heteroaromatic compounds / Organic carbonic acids and derivatives / Azacyclic compounds
show 6 more
Substituents
Pyrazolopyridine / Aminopyrimidine / Halobenzene / Fluorobenzene / Aryl fluoride / Aryl halide / Pyridine / Pyrimidine / Benzenoid / Imidolactam
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, carbamate ester, aminopyrimidine, pyrazolopyridine (CHEBI:76018)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
Stimulator
General Function
Heme binding
Specific Function
Has guanylyl cyclase on binding to the beta-1 subunit.Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
Gene Name
GUCY1A2
Uniprot ID
P33402
Uniprot Name
Guanylate cyclase soluble subunit alpha-2
Molecular Weight
81749.185 Da
References
  1. Soeiro-Pereira PV, Falcai A, Kubo CA, Oliveira-Junior EB, Marques OC, Antunes E, Condino-Neto A: BAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes. Br J Pharmacol. 2012 Jul;166(5):1617-30. doi: 10.1111/j.1476-5381.2011.01764.x. [PubMed:22044316]
  2. Humbert M, Ghofrani HA: The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax. 2016 Jan;71(1):73-83. doi: 10.1136/thoraxjnl-2015-207170. Epub 2015 Jul 28. [PubMed:26219978]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
Molecular Weight
57610.165 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Khaybullina D, Patel A, Zerilli T: Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58. [PubMed:25395817]

Drug created on November 13, 2013 16:07 / Updated on May 26, 2018 08:59