Riociguat

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).

• Adempas is a soluble guanylate cyclase (sGC) stimulator 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. ( 1.1 ) • Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.ICD-10: I27.0

• • Pregnancy ( 4.1 ) • Use with nitrates or nitric oxide donors in any form ( 4.2 , 7.1 ) • Use with PDE inhibitors ( 2.6 , 4.3 , 7.1 ) • Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators. ( 4.4 , 7.1 ) • • Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP) ( 4.4 ) 4.1 Pregnancy Based on data from animal reproduction studies, Adempas may cause fetal harm when administered to a pregnant woman and is contraindicated in females who are pregnant.contraindicated

• Initiate treatment at 1 mg taken three times a day. ( 2.1 ) • For patients who may not tolerate the hypotensive effect of Adempas, consider a starting dose of 0.5 mg, three times a day. ( 2.1 ) • Increase dosage by 0.5 mg at intervals of no sooner than 2-weeks as tolerated to a maximum of 2.5 mg three times a day. ( 2.1 ) • Tablets may be crushed and mixed with water or soft foods for patients who have difficulty swallowing. ( 2.1 ) 2.1 Recommended Dosage in Adult Patients The recommended starting dosage is 1 mg taken 3 times a day. For patients who may not tolerate the hypotensive effect of Adempas, consider a starting dose of 0.5 mg taken three times a day. If systolic blood pressure remains greater than 95 mmHg and the patient has no signs or symptoms of hypotension, up-titrate the dose by 0.5 mg taken three times a day. Dose increases should be no sooner than 2 weeks apart. The dose can be increased to the highest tolerated dosage, up to a maximum of 2.5 mg taken three times a day. If at any time, the patient has symptoms of hypotension, decrease the dosage by 0.5 mg taken three times a day. Crushed Tablets For patients who are unable to swallow whole tablets, Adempas may be crushed and mixed with water or soft foods (such as applesauce) immediately before administration [see Clinical Pharmacology ( 12.3 )] . 2.2 Dosage Interruption If a dose is missed, advise patients to continue with the next regularly scheduled dose. In case Adempas is interrupted for 3 days or more, re-titrate Adempas.

• Symptomatic hypotension ( 5.3 ) • Bleeding ( 5.4 ) • Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment ( 5.5 ) 5.1 Embryo-Fetal Toxicity Based on data from animal reproduction studies, Adempas may cause embryo-fetal toxicity when administered to a pregnant female and is contraindicated in females who are pregnant. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment, monthly during treatment, and for one month after stopping treatment. Advise females of reproductive potential to use effective contraception during treatment with ADEMPAS and for at least one month after the last dose [see Dosage and Administration ( 2.3 ) and Use in Specific Populations ( 8.1 , 8.3 )] . For females, Adempas is only available through a restricted program under the Adempas REMS Program [see Warnings and Precautions ( 5.2 )] . 5.2 Adempas REMS Program Females can only receive Adempas through the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program, a restricted distribution program [see Warnings and Precautions ( 5.1 )]. Important requirements of the Adempas REMS Program include the following: • Prescribers must be certified with the program by enrolling and completing training. • All females, regardless of reproductive potential, must enroll in the Adempas REMS Program prior to initiating Adempas. Male patients are not enrolled in the Adempas REMS Program.

The following serious adverse reactions are discussed elsewhere in the labeling: • Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.1 )] • Hypotension [see Warnings and Precautions ( 5.3 )] • Bleeding [see Warnings and Precautions ( 5.4 )] Adverse reactions occurring more frequently (≥3%) on Adempas compared to placebo are headache, dyspepsia/gastritis, dizziness, nausea, diarrhea, hypotension, vomiting, anemia, gastroesophageal reflux, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure to Adempas in two, randomized, double blind, placebo-controlled trials in patients with inoperable or recurrent/persistent CTEPH (CHEST-1) and treatment naive or pre-treated PAH patients (PATENT-1). The population (Adempas: n = 490; Placebo: n = 214) was between the age of 18 and 80 years [see Clinical Studies ( 14.1 , 14.2 )]. The safety profile of Adempas in patients with inoperable or recurrent/persistent CTEPH (CHEST-1) and treatment naive or pre-treated PAH (PATENT-1) were similar.

• Lactation: Advise not to breastfeed. ( 8.2 ) • Renal impairment: Not recommended in patients with creatinine clearance <15 mL/min or on dialysis. ( 8.7 ) • Hepatic impairment: Not recommended in patients with severe (Child Pugh C) hepatic impairment. ( 8.8 ) • Smoking: May require dosages higher than 2.5 mg three times a day if tolerated. Dose decrease may be required in patients who stop smoking. ( 2.4 , 7.2 ) 8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, Adempas may cause embryo-fetal toxicity and miscarriage when administered to a pregnant woman and is contraindicated during pregnancy [see Contraindications (4.1)] . There are limited available data with ADEMPAS use in pregnant women. In animal reproduction studies, oral administration of riociguat to pregnant rats during organogenesis was teratogenic and embryotoxic at exposures approximately 8 times and 2 times, respectively, the human exposure. In reproduction studies with pregnant rabbits, oral administration of riociguat during organogenesis caused abortions and fetal toxicity at exposures approximately 4 times and 13 times, respectively, the maximum recommended human dose (MRHD). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

Riociguat pharmacokinetics are dose proportional from 0.5 to 2.5 mg. Inter-individual variability of riociguat exposure (AUC) across all doses is approximately 60%, and within-subject variability is approximately 30%.

In cases of overdose, blood pressure should be closely monitored and supported as appropriate. Based on extensive plasma protein binding, riociguat is not expected to be dialyzable.

• Oct 8, 2013NDANDA204819Bayer Hlthcare

1. 1Dyspnoea5,64218%
2. 2Death5,36617%
3. 3Headache4,44814%
4. 4Nausea3,72012%
5. 5Diarrhoea3,48911%
6. 6Dizziness3,47011%
7. 7Hypotension3,35211%
8. 8Fatigue2,9179.2%
9. 9Hospitalisation2,2977.2%
10. 10Vomiting2,0886.6%
11. 11Oedema Peripheral1,7705.6%
12. 12Cough1,7605.5%
13. 13Pneumonia1,7495.5%
14. 14Fluid Retention1,7435.5%
15. 15Malaise1,6545.2%

The 10 most recently updated of 70 ClinicalTrials.gov registrations naming Riociguat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty
  Not yet recruiting · Phase 3 · Interventional · 150 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT07644377updated 2026-06-12
• Pulmonary Hypertension: Intensification and Personalisation of Combination Rx
  Recruiting · Phase 4 · Interventional · 40 enrolled · Sheffield Teaching Hospitals NHS Foundation Trust
  NCT05825417updated 2026-06-05
• Riociguat in Children With Pulmonary Arterial Hypertension (PAH)
  Active not recruiting · Phase 3 · Interventional · 24 enrolled · Bayer
  NCT02562235updated 2026-05-12
• Treatment of Exercise-Induced Pulmonary Vascular Dysfunction After Pulmonary Thromboendarterectomy or Balloon Pulmonary Angioplasty
  Completed · Phase 2 · Interventional · 10 enrolled · University of Colorado, Denver
  NCT03409588updated 2026-02-05
• Riociguat in Triple Therapy for Pulmonary Arterial Hypertension in Real-World Practice
  Not yet recruiting · Observational · 15 enrolled · Caio Júlio César dos Santos Fernandes
  NCT07374302updated 2026-01-28
• A Study of Sotatercept for Patients With Eisenmenger Syndrome or Unrepaired Shunt-Associated Pulmonary Arterial Hypertension Resistant to Vasodilator Therapy
  Recruiting · Phase 4 · Interventional · 36 enrolled · Kazuya Hosokawa
  NCT07356778updated 2026-01-21
• Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH
  Terminated · Phase 2 · Interventional · 35 enrolled · Heidelberg University
  NCT05339087updated 2026-01-21
• Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH
  Recruiting · Phase 3 · Interventional · 15 enrolled · Dr Sudarshan Rajagopal
  NCT05140525updated 2025-10-21
• A Long-term Extension Study of Riociguat in Patients With Symptomatic Pulmonary Arterial Hypertension.
  Completed · Phase 4 · Interventional · 18 enrolled · Bayer
  NCT02759419updated 2025-10-03
• Effects of Riociguat on RIght VEntricular Size and Function in PAH and CTEPH
  Terminated · Phase 4 · Interventional · 30 enrolled · Heidelberg University
  NCT04954742updated 2025-09-15

Frequently asked questions

How does Riociguat work?

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).

What is Riociguat used for?

According to FDA labeling, Riociguat carries indications including: Adempas is a soluble guanylate cyclase (sGC) stimulator 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. ( 1.1 ) • Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Riociguat?

Riociguat is classified as Antihypertensives for pulmonary arterial hypertension, Soluble Guanylate Cyclase Stimulator, Guanylate Cyclase Stimulators, Phosphodiesterase 5 Inhibitors, Vasodilation.

What are the brand names for Riociguat?

Riociguat is marketed under brand names including Adempas.

What are the contraindications for Riociguat?

Riociguat labeling lists contraindications including: • Pregnancy ( 4.1 ) • Use with nitrates or nitric oxide donors in any form ( 4.2 , 7.1 ) • Use with PDE inhibitors ( 2.6 , 4.3 , 7.1 ) • Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators. ( 4.4 , 7.1 ) • • Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP) ( 4.4 ) 4.1 Pregnancy Based on data from animal reproduction studies, Adempas may cause fetal harm when administered to a pregnant woman and is contraindicated in females who are pregnant.. Always consult the full prescribing information and a clinician.