Drug information of riociguat
Mechanism of effect
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.
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
95% with serum albumin and alpha-1–acidic glycoprotein being the main binding components.
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%).
About 12 hours in patients and 7 hours in healthy subjects.
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
Initial dose: 1 mg PO TID; consider 0.5 mg PO TID if patient may not tolerate hypotensive effect
If systolic blood pressure >95 mmHg and no symptoms of hypotension, up-titrate dose by 0.5 mg PO TID with dose increases no sooner than 2 weeks apart to highest tolerated dose (not to exceed 2.5 mg PO TID)
Pregnancy (see Black Box Warnings)
Coadministration with nitrates or nitric oxide donors (eg, amyl nitrite), PDE inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil), or nonspecific PDE inhibitors (eg, dipyridamole, theophylline) because of additive hypotension
Administration within 24 hr of sildenafil
Tatalafil 24 hr before or within 48 hr after riociguat
Prevent pregnancy during treatment and for 1 month after stopping treatment
Dyspepsia and gastritis (21%)
Serious bleeding (2.4%)
InteractionsRanolazine , Mefloquine , Amyl Nitrite , Tipranavir , Ulipristal , Etravirine , Dabrafenib , Eltrombopag , cobicistat , Paliperidone , Roflumilast , Amiodarone , Erythromycin , isosorbide dinitrate , Isoniazid , Imatinib , Propafenone , lasmiditan , vemurafenib , voxelotor , Erdafitinib , Apalutamide , ivosidenib , Avanafil , Darolutamide , conivaptan , Lopinavir , Quinine , Indinavir , Idelalisib , Ponatinib , Nicardipine , saquinavir , nelfinavir , Fosamprenavir , Mifepristone , Afatinib , vandetanib , Grapefruit , Lomitapide , Nefazodone , dronedarone , ritonavir , isosorbide mononitrate , Carvedilol , Ketoconazole , Chloramphenicol , Darunavir , Tamoxifen , Quinidine , Nitroglycerin , Nifedipine , Nilotinib , Vardenafil , Verapamil , Voriconazole , Sunitinib , Sildenafil , Simvastatin , Cyclosporine , Lapatinib , Lovastatin , Propranolol , Pantoprazole , Posaconazole , Tadalafil , Tacrolimus , Dipyridamole , Oxtriphylline , Gefitinib , Cannabidiol , ambrisentan , Nesiritide
- amyl nitrite
- isosorbide dinitrate
- isosorbide mononitrate
- nitroglycerin IV
- nitroglycerin PO
- nitroglycerin sublingual
- nitroglycerin transdermal
- nitroglycerin translingual
Serious - Use Alternative (66)
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
- erythromycin base
- erythromycin ethylsuccinate
- erythromycin lactobionate
- erythromycin stearate
- progesterone micronized
Contraindicated in pregnant females because it may cause fetal harm
In 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 1 month after stopping treatment by using acceptable methods of contraception (ie, 1 highly effective form of contraception [IUD, contraceptive implants, or tubal sterilization] or a combination of methods (hormone method with a barrier method or 2 barrier methods)
Available to females only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program
Based on data from animal reproduction studies, therapy may cause embryo-fetal toxicity and miscarriage when administered to a pregnant woman and is contraindicated during pregnancy; in reproduction studies with pregnant rabbits, oral administration during organogenesis caused abortions and fetal toxicity at exposures approximately 4 times and 13 times, respectively, the maximum recommended human (MRHD); advise pregnant women of the potential risk to a fetus
Females of reproductive potential must have a negative pregnancy test before initiation, monthly during, and 1 month after discontinuation of treatment; contraception must also be used during and for 1 month after treatment (see Boxed Warning)
If pregnancy suspected, contact healthcare provider immediately