Dosing & Uses
Dosage Forms & Strengths
tablet
- 0.5mg
- 1mg
- 1.5mg
- 2mg
- 2.5mg
Chronic-thromboembolic Pulmonary Hypertension (CTEPH)/ Arterial Pulmonary Hypertension (PAH)
Indicated for persistent/recurrent CTEPH, (WHO Group 4) after surgical treatment or inoperable CTEPH, to improve exercise capacity and WHO functional class
Indicated for PAH, (WHO Group 1), to improve exercise capacity, WHO functional class and to delay clinical worsening
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)
If symptoms of hypotension occur, decrease dose by 0.5 mg TID
Dosing considerations
- Obtain pregnancy tests prior to start of treatment and monthly during treatment
Dosage Modifications
Smoking: Consider titrating to dosage higher than 2.5 mg PO TID if tolerated; a dose decrease may be required in patients who stop smoking
Coadministration with strong CYP and P-gp/BCRP inhibitors: Consider lower initial dose of 0.5 mg PO TID
CrCl <15 mL/min or dialysis: Safety and efficacy have not been demonstrated
Severe hepatic impairment (Child Pugh C): Safety and efficacy have not been demonstrated
-
Transitioning to and from riociguat therapy
- Discontinue sildenafil at least 24 hours prior to initiating dosing
- Discontinue tadalafil at least 48 hours prior to initiating dosing [
- Consider initiating therapy at a starting dose of 0.5 mg in patients at risk of hypotension
- Monitor for signs and symptoms of hypotension on initiation.
- Discontinue riociguat therapy at least 24 hours prior to administering a PDE5-inhibitor
- Monitor for signs and symptoms of hypotension on initiation.
Orphan Designations
Systemic sclerosis
Fontan-palliated patients
Sponsor
- Bayer HealthCare Pharmaceuticals; 100 Bayer Blvd, P. O. Box 915; Whippany, NJ 07981-0915
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (15)
- amyl nitrite
amyl nitrite, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- avanafil
avanafil, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.
- dipyridamole
dipyridamole, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nonspecific PDE-5 inhibitors (eg, dipyridamole, theophylline) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.
- isosorbide dinitrate
isosorbide dinitrate, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- isosorbide mononitrate
isosorbide mononitrate, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- nitroglycerin IV
nitroglycerin IV, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- nitroglycerin PO
nitroglycerin PO, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- nitroglycerin sublingual
nitroglycerin sublingual, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- nitroglycerin transdermal
nitroglycerin transdermal, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- nitroglycerin translingual
nitroglycerin translingual, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nitrates or nitric oxide donors is contraindicated due to risk of hypotension.
- sildenafil
sildenafil, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension; do not administer within 24 hr of each other.
- tadalafil
tadalafil, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension; do not administer 24 hr before or within 48hr of each other.
- theophylline
theophylline, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nonspecific PDE-5 inhibitors (eg, dipyridamole, theophylline) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.
- vardenafil
vardenafil, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.
- vericiguat
riociguat, vericiguat. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Vericiguat is contraindicated with use of other soluble guanylate cyclase (sGC) stimulators.
Serious - Use Alternative (72)
- afatinib
afatinib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- amiodarone
amiodarone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- amobarbital
amobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- atorvastatin
atorvastatin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- azithromycin
azithromycin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- carvedilol
carvedilol will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- cobicistat
cobicistat will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- conivaptan
conivaptan will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
conivaptan will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - cyclosporine
cyclosporine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (BCRP/ABCG2 substrate) with BCRP/ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed.
cyclosporine will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - dabrafenib
dabrafenib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- darolutamide
darolutamide will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- darunavir
darunavir will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
darunavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
darunavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - dipyridamole
dipyridamole will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
dipyridamole will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - dronedarone
dronedarone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- eltrombopag
eltrombopag will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - erdafitinib
erdafitinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- erythromycin base
erythromycin base will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- erythromycin stearate
erythromycin stearate will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- etravirine
etravirine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- fexinidazole
fexinidazole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fosamprenavir
fosamprenavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- grapefruit
grapefruit will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- idelalisib
idelalisib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- imatinib
imatinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
imatinib will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - indinavir
indinavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- isoniazid
isoniazid will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- itraconazole
itraconazole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
ketoconazole will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
ketoconazole will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - lapatinib
lapatinib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
lapatinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - lasmiditan
lasmiditan increases levels of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
lasmiditan increases levels of riociguat by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates. - lomitapide
lomitapide will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- lonafarnib
lonafarnib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
lopinavir will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
lopinavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
lopinavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - lovastatin
lovastatin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- mefloquine
mefloquine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- mifepristone
mifepristone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- nefazodone
nefazodone will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- nelfinavir
nelfinavir will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
nelfinavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
nelfinavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - nicardipine
nicardipine will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- nifedipine
nifedipine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- nilotinib
nilotinib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- paliperidone
paliperidone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- pantoprazole
pantoprazole will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- ponatinib
ponatinib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
ponatinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - posaconazole
posaconazole will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
posaconazole will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - progesterone micronized
progesterone micronized will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- propafenone
propafenone will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- propranolol
propranolol will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- quinidine
quinidine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
quinidine will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - quinine
quinine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- ranolazine
ranolazine will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- ritonavir
ritonavir will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
ritonavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
ritonavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - saquinavir
saquinavir will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
saquinavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
saquinavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - simvastatin
simvastatin will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- sotorasib
sotorasib will decrease the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- sunitinib
sunitinib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
sunitinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - tacrolimus
tacrolimus will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- tamoxifen
tamoxifen will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- tepotinib
tepotinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- tipranavir
tipranavir will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- tucatinib
tucatinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- ulipristal
ulipristal will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- vandetanib
vandetanib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
vandetanib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - vemurafenib
vemurafenib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- verapamil
verapamil will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- voriconazole
voriconazole will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- voxelotor
voxelotor will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (74)
- abacavir
abacavir will increase the level or effect of riociguat by unknown mechanism. Modify Therapy/Monitor Closely. Riociguat dose reduction may be necessary
- acalabrutinib
acalabrutinib increases levels of riociguat by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- aluminum hydroxide
aluminum hydroxide decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- aluminum hydroxide/magnesium carbonate
aluminum hydroxide/magnesium carbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- aluminum hydroxide/magnesium trisilicate
aluminum hydroxide/magnesium trisilicate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- apalutamide
apalutamide will decrease the level or effect of riociguat by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- atazanavir
atazanavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 0.5 mg 3 times a day when initiating riociguat in patients receiving atazanavir (a strong CYP3A4 and P-gp inhibitor). Monitor for signs and symptoms of hypotension on initiation and on treatment with atazanavir.
- benazepril
riociguat, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.
- berotralstat
berotralstat will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- bosentan
bosentan will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- calcium carbonate
calcium carbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- cannabidiol
cannabidiol will increase the level or effect of riociguat by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.
- captopril
riociguat increases effects of captopril by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.
- carbamazepine
carbamazepine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- cenobamate
cenobamate will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- cigarette smoking
cigarette smoking will decrease the level or effect of riociguat by increasing metabolism. Modify Therapy/Monitor Closely. Consider titrating riociguat to dosage >2.5 mg PO TID if tolerated; may need to decrease dose if quit smoking
- cilostazol
riociguat, cilostazol. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Riociguat is contraindicated with specific PDE-5 inhibitors (eg sildenafil, tadalafil, vardenafil) and nonspecific PDE-5 inhibitors (eg theophylline, dipyridamole) due to risk of hypotension; data are limited with other PDE inhibitors (eg, milrinone, cilostazol, roflumilast).
- citric acid/sodium bicarbonate
citric acid/sodium bicarbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- clarithromycin
clarithromycin will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dabrafenib
dabrafenib will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- dexamethasone
dexamethasone will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- diltiazem
riociguat, diltiazem. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Monitor patients closely for additive hypotensive effects if two or more of these agents are combined.
- efavirenz
efavirenz will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- elagolix
elagolix will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
elagolix decreases levels of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed. - eliglustat
eliglustat increases levels of riociguat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- eluxadoline
eluxadoline increases levels of riociguat by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.
- encorafenib
encorafenib, riociguat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- enzalutamide
enzalutamide will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- esomeprazole
esomeprazole will decrease the level or effect of riociguat by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- fedratinib
fedratinib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fosphenytoin
fosphenytoin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- fostamatinib
fostamatinib will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp/BCRP substrate drugs. Monitor for toxicities of P-gp/BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- fostemsavir
fostemsavir will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.
- indinavir
indinavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
istradefylline will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates. - itraconazole
itraconazole will increase the level or effect of riociguat by decreasing metabolism. Modify Therapy/Monitor Closely. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
itraconazole will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Coadministration of riociguat (an ABCG2 [BCRP] substrate) with strong ABCG2 inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - lonafarnib
lonafarnib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- lorlatinib
lorlatinib will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- magnesium hydroxide
magnesium hydroxide decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- magnesium oxide
magnesium oxide decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- milrinone
milrinone, riociguat. Either increases effects of the other by additive vasodilation. Modify Therapy/Monitor Closely. Riociguat is contraindicated with specific PDE-5 inhibitors (eg sildenafil, tadalafil, vardenafil) and nonspecific PDE-5 inhibitors (eg theophylline, dipyridamole) due to risk of hypotension; data are limited with other PDE inhibitors.
- mitotane
mitotane decreases levels of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- nafcillin
nafcillin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- nefazodone
nefazodone will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nevirapine
nevirapine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- omeprazole
omeprazole will decrease the level or effect of riociguat by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- pentobarbital
pentobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- phenobarbital
phenobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- phenytoin
phenytoin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- primidone
primidone will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- regorafenib
regorafenib will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.
- rifabutin
rifabutin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- rifampin
rifampin will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- rifapentine
rifapentine will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- roflumilast
riociguat, roflumilast. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Riociguat is contraindicated with specific PDE-5 inhibitors (eg sildenafil, tadalafil, vardenafil) and nonspecific PDE-5 inhibitors (eg theophylline, dipyridamole) due to risk of hypotension; data are limited with other PDE inhibitors (eg, milrinone, cilostazol, roflumilast).
- rucaparib
rucaparib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- safinamide
safinamide will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.
- sarecycline
sarecycline will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- smoking
smoking will decrease the level or effect of riociguat by increasing metabolism. Modify Therapy/Monitor Closely. Consider titrating riociguat to dosage >2.5 mg PO TID if tolerated; may need to decrease dose if quit smoking
- sodium bicarbonate
sodium bicarbonate decreases levels of riociguat by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by at least 1 hour.
- sofosbuvir/velpatasvir
sofosbuvir/velpatasvir will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.
- St John's Wort
St John's Wort will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment
- stiripentol
stiripentol, riociguat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
stiripentol will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.
stiripentol will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol. - tafamidis
tafamidis will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tafamidis meglumine
tafamidis meglumine will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tazemetostat
tazemetostat will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will increase the level or effect of riociguat by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.
tecovirimat will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered. - tipranavir
tipranavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tucatinib
tucatinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
Minor (1)
- ribociclib
ribociclib will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10%
Headache (27%)
Dyspepsia and gastritis (21%)
Dizziness (20%)
Nausea (14%)
Diarrhea (12%)
1-10%
Hypotension (10%)
Vomiting (10%)
Anemia (7%)
GERD (5%)
Constipation (5%)
Serious bleeding (2.4%)
Hemoptysis (1%)
Warnings
Black Box Warnings
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
Contraindications
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
Concomitant use of other soluble guanylate cyclase (sGC) stimulators
Tadalafil 24 hr before or within 48 hr after riociguat
Patients with pulmonary hypertension associated with idiopathic interstitial pneumonia
Cautions
May cause fetal harm when administered during pregnancy and is contraindicated for use in women who are pregnant (see Black Box Warnings and Contraindications); because of this, females may only receive riociguat via a restricted access program
Reduces blood pressure; consider the potential for symptomatic hypotension or ischemia in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, or autonomic dysfunction; dose reduction may be required
Coadministration with strong CYP and P-gp/BCRP inhibitors increases riociguat systemic exposure and increases risk for hypotension; dose reduction may be required
Serious bleeding reported including hemoptysis, vaginal bleeding, catheter site hemorrhage, subdural hematoma, hematemesis, and intra-abdominal hemorrhage
Pulmonary vasodilators may significantly worsen cardiovascular status of patients with pulmonary veno-occlusive disease; avoid use in these patients and discontinue if signs of pulmonary edema occur and are confirmed
Adempas REMS Program
- Females can only receive drug through the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program, a restricted distribution program
- Important requirements of the Adempas REMS Program include the following:
- Prescribers must be certified with program by enrolling and completing training.
- All females, regardless of reproductive potential, must enroll in Adempas REMS Program prior to initiating therapy
- Male patients are not enrolled in the Adempas REMS Program
- Female patients of reproductive potential must comply with the pregnancy testing and contraception requirements
- Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive Adempas
- Further information, including a list of certified pharmacies, is available at www.AdempasREMS.com or 1-855-4 ADEMPAS
Pregnancy & Lactation
Pregnancy
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
Lactation
There are no data on presence of riociguat in human milk, effects on breastfed infant, or on milk production; drug is present in rat milk; because of potential for serious adverse reactions, such as hypotension, in breastfed infants, advise women not to breastfeed during therapy
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Stimulates soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO)
NO binds to sGC and catalyzes synthesis of cGMP, which in turn activates protein kinase G regulation of cytosolic calcium ion concentration; this cascade changes actin-myosin contractility resulting in vasodilation
PAH is associated with endothelial dysfunction, impaired synthesis of NO and insufficient stimulation of the NO-sGC-cGMP pathway
Elicits a dual mode of action; riociguat sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding, and also directly stimulates sGC via a different binding site, independently of NO
Absorption
Bioavailability: 94%
Peak plasma time: 1.5 hr
Food does not affect bioavailability
Distribution
Protein bound: 95%; primarily to albumin and alpha-1-acidic glycoprotein
Vd: 30 L
Metabolism
Mainly metabolized by CYP1A1, CYP3A, CYP2C8, and CYP2J2
Substrate of P-gp (ABCB1) and BCRP (ABCG2) efflux transporter proteins
Active metabolite: Formation of the major active metabolite (M1) is catalyzed by CYP1A1; M1 is 10-33% as potent as riociguat; M1 is further metabolized to the inactive N-glucuronide
Elimination
Half-life: 12 hr ((patients with PAH); 7 hr (healthy individuals)
Systemic clearance: 1.8 L/hr (patients with PAH); 3.4 L/hr (healthy individuals)
Excretion: 40% urine; 53% feces
Administration
Oral Administration
Antacids (eg, aluminum hydroxide/magnesium hydroxide) decrease riociguat absorption and should not be taken within 1 hr of taking riociguat
If a dose is missed, continue with next regularly scheduled dose
If dosage interrupted for >3 days, retitrate dose
Patients who are unable to swallow whole tablets, may crush them and mix them with water or soft foods (such as applesauce) immediately before administration
Images
Patient Handout
riociguat oral
RIOCIGUAT - ORAL
(RYE-oh-SIG-ue-at)
COMMON BRAND NAME(S): Adempas
WARNING: Riociguat must not be used during pregnancy. It may harm an unborn baby. It is important to prevent pregnancy while taking this medication and for 1 month after treatment. Female patients must use reliable birth control during treatment and for 1 month after the end of treatment. Ask your doctor which forms of birth control to use while taking this medication. Female patients must take a pregnancy test before starting treatment, take a monthly pregnancy test during treatment, and take a pregnancy test 1 month after the end of treatment. If you become pregnant or think you may be pregnant, tell your doctor right away.To receive this medication, all doctors, pharmacists, and female patients must understand, agree to, and carefully follow the requirements of the Adempas REMS program developed by the FDA. These requirements apply to female patients in the United States only. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.
USES: Riociguat is used to treat high blood pressure in the lungs (pulmonary hypertension). It can also be used to treat a certain type of high blood pressure in the lungs caused by blood clots (chronic thromboembolic pulmonary hypertension) when surgery has not been fully successful or is impossible. Riociguat works by relaxing and widening the blood vessels in your lungs so blood can flow more easily. Decreasing high blood pressure in the lungs allows your heart and lungs to work better and improves your ability to exercise.
HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking riociguat and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually 3 times daily. The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Take this medication 1 hour before or after taking antacids that contain aluminum or magnesium. These products prevent your body from fully absorbing riociguat.To reduce your risk of side effects (such as low blood pressure), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Do not increase your dose or use this drug more often than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Tell your doctor if your condition does not improve or if it worsens.
SIDE EFFECTS: Headache, dizziness, lightheadedness, fainting, unusual tiredness, heartburn, indigestion, nausea, vomiting, or diarrhea may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication has rarely caused serious bleeding. If you notice any of the following unlikely but serious signs of bleeding, tell your doctor right away: unusual bleeding from the vagina, coughing up blood, bleeding around catheter site, signs of stomach/intestinal bleeding (such as black/bloody stools, vomit that contains blood or looks like coffee grounds), signs of bleeding in the brain (such as severe headache, weakness on one side of the body, vision problems, trouble speaking, confusion).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking riociguat, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: smoking or history of smoking, low or high blood pressure, other lung conditions (such as pulmonary veno-occlusive disease, idiopathic interstitial pneumonia), dehydration, a severe blockage of blood flow out of the heart.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication must not be used during pregnancy. It may harm an unborn baby. See also Warning section.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: See also How To Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: aminophylline, certain drugs used to treat chest pain/angina or high blood pressure (nitrates such as nitroglycerin, isosorbide), dipyridamole, drugs to treat erectile dysfunction-ED/pulmonary hypertension (such as sildenafil, tadalafil, vardenafil), recreational drugs called "poppers" containing amyl or butyl nitrite, theophylline.Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as blood pressure, pregnancy tests) must be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up. Check with your doctor if you miss doses for more than 3 days in a row.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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