Riociguat
Soluble guanylate cyclase (sGC) stimulators
Soluble guanylate cyclase (sGC) stimulatorsPregnancy: contraindicated
Contraindicated: it may harm the fetus; a negative pregnancy test is required before starting, monthly during treatment and for a month after, with reliable contraception.
An oral sGC stimulator that relaxes lung arteries through cGMP. Used in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
Quick facts
- Group
- Soluble guanylate cyclase (sGC) stimulators
- Target
- Soluble guanylate cyclase (α1β1), the nitric oxide receptor
- Used for
- Pulmonary arterial hypertension
- Key effects
- Headache and dizziness · Dyspepsia · Peripheral oedema
- Monitor
- Blood pressure and signs of hypotension · Haemoglobin
- ATC
- C02KX05
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows riociguat bound to human soluble guanylate cyclase (with NO bound), at the stimulator site of the β1 subunit.
Soluble guanylate cyclase makes cGMP when nitric oxide binds its haem. In pulmonary hypertension NO signalling is weak. Riociguat binds a separate site on the enzyme: it stimulates sGC directly, even without NO, and sensitizes it to the NO that is present. cGMP rises, pulmonary artery smooth muscle relaxes and pulmonary vascular resistance falls; antiproliferative effects are also described.
- Binds sGC at a site separate from nitric oxide
- Stimulates the enzyme and sensitizes it to NO
- cGMP rises in vascular smooth muscle
- Lung arteries relax; pulmonary vascular resistance falls
Indications
- Pulmonary arterial hypertension, to improve exercise capacity and slow worsening Pulmonary hypertension and cor pulmonale →
- Chronic thromboembolic pulmonary hypertension (CTEPH) that cannot be operated on or persists after surgery Pulmonary hypertension and cor pulmonale →
Adverse effects
Common
- Headache and dizziness
- Dyspepsia, nausea, vomiting, diarrhoea, constipation
- Peripheral oedema
- Anaemia
- Hypotension
Contraindications
- Pregnancy
- Nitrates or nitric oxide donors (such as amyl nitrite) in any form
- PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) and nonspecific PDE inhibitors (dipyridamole, theophylline)
- Other sGC stimulators (vericiguat)
- Pulmonary hypertension associated with idiopathic interstitial pneumonia
Key interactions
- Nitrates, NO donors, PDE-5 inhibitors, dipyridamole, theophylline
- Severe hypotension; contraindicated, with time gaps when switching from sildenafil or tadalafil.
- Strong CYP and P-gp/BCRP inhibitors (ketoconazole, itraconazole, ritonavir)
- Raise riociguat levels and the risk of hypotension.
- Strong inducers (carbamazepine, phenytoin, phenobarbital, St John's wort)
- May lower riociguat levels.
- Smoking
- Lowers riociguat levels by inducing CYP1A1; stopping smoking can raise them.
- Aluminium or magnesium antacids
- Reduce absorption; taken at least an hour apart.
What is monitored
- Blood pressure and signs of hypotension, especially when the dose is raised
- Monthly pregnancy tests in people who could become pregnant
- Haemoglobin
- Smoking status
- Haemoptysis and signs of pulmonary oedema
Administration and safety
- Oral tablet, three times a day, with or without food; can be crushed and mixed with water or soft food just before use.
- Started low and adjusted every two weeks according to blood pressure and tolerance.
- Antacids are separated by at least one hour.
- Under a restricted-distribution programme for people who can become pregnant (pregnancy testing and contraception).
Pregnancy and breastfeeding
Contraindicated: it may harm the fetus; a negative pregnancy test is required before starting, monthly during treatment and for a month after, with reliable contraception.
Nursing care
- Before: pregnancy test, blood pressure, list of nitrates or PDE-5 inhibitors, smoking status.
- During: blood pressure and symptoms of hypotension at each dose change; monthly pregnancy test.
- Teach to never use nitroglycerin, amyl nitrite ('poppers') or erectile dysfunction drugs.
- Teach to report coughing up blood, fainting or chest pain, and any change in smoking.
Pharmacokinetics
- Absorption
- Oral; food does not change bioavailability; tablets may be crushed in water or soft food.
- Metabolism
- CYP1A1, CYP3A4, CYP3A5 and CYP2J2; CYP1A1, induced by tobacco smoke, makes the main active metabolite.
- Elimination
- In urine and faeces.
- Onset and duration
- Started low and raised gradually every two weeks according to blood pressure and tolerance.
Test yourself
Think of the answer, then tap the question to see it.
Why is riociguat contraindicated with sildenafil?
Both raise cGMP, by stimulating its production and by slowing its breakdown, causing severe hypotension.
How does smoking affect riociguat?
Tobacco smoke induces CYP1A1 and lowers riociguat levels; quitting smoking can raise them.
Which form of pulmonary hypertension is treated by riociguat in addition to PAH?
Chronic thromboembolic pulmonary hypertension (CTEPH), inoperable or persistent after surgery.
What test is done monthly in women who could become pregnant on riociguat, and why?
A pregnancy test, because riociguat causes embryo-fetal toxicity.
Connections
← Back to the class: Soluble guanylate cyclase (sGC) stimulators
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Riociguat: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); DailyMed - RIOCIGUAT tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Structure of huamn soluble guanylate cyclase in the riociguat and NO-bound state (RCSB Protein Data Bank, 2021); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.