[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Soluble guanylate cyclase (sGC) stimulators](https://durgical.com/en/pharmacology/classes/soluble-guanylate-cyclase-stimulators/) › Riociguat

# Riociguat

## Soluble guanylate cyclase (sGC) stimulators?

Soluble guanylate cyclase (sGC) stimulators

## Pregnancy: 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.

Updated Nov 1, 2026

## Quick facts

**Group**
[Soluble guanylate cyclase (sGC) stimulators](https://durgical.com/en/pharmacology/classes/soluble-guanylate-cyclase-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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**Soluble guanylate cyclase (α1β1), the nitric oxide receptor**Riociguat

ⓘ The figure shows riociguat bound to human soluble guanylate cyclase (with NO bound), at the stimulator site of the β1 subunit.

**Target in 3D:** Soluble guanylate cyclase (α1β1), the nitric oxide receptor. PDB structure 7D9R (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7D9R) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/pulmonary-hypertension-and-cor-pulmonale/)
- Chronic thromboembolic pulmonary hypertension (CTEPH) that cannot be operated on or persists after surgery [Pulmonary hypertension and cor pulmonale →](https://durgical.com/en/conditions/pulmonary-hypertension-and-cor-pulmonale/)

## Adverse effects

### Common

- Headache and dizziness
- Dyspepsia, nausea, vomiting, diarrhoea, constipation
- Peripheral oedema
- Anaemia
- Hypotension

### Serious (rare, important)

- Embryo-fetal toxicity
- Symptomatic hypotension and fainting
- Bleeding, including from the lungs (haemoptysis)
- Pulmonary oedema in pulmonary veno-occlusive disease

## 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.

## Memory aid

RIOciguat 'switches on' the NO receptor in the lungs. Three 'no's: NO nitrates, NO sildenafil, NO pregnancy.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/riociguat/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**Pregnancy: 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.

## Connections

## Related drugs 1

- [Vericiguat](https://durgical.com/en/pharmacology/vericiguat/)

## Related conditions 1

- [Pulmonary hypertension and cor pulmonale](https://durgical.com/en/conditions/pulmonary-hypertension-and-cor-pulmonale/)

[← Back to the class: Soluble guanylate cyclase (sGC) stimulators](https://durgical.com/en/pharmacology/classes/soluble-guanylate-cyclase-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](https://medlineplus.gov/druginfo/meds/a615005.html) (MedlinePlus (U.S. National Library of Medicine), 2023); [DailyMed - RIOCIGUAT tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8092c64b-e240-43c3-9d2e-e0dd7708d96f) (DailyMed (U.S. National Library of Medicine), 2026); [Structure of huamn soluble guanylate cyclase in the riociguat and NO-bound state](https://www.rcsb.org/structure/7D9R) (RCSB Protein Data Bank, 2021); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=C02KX05) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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