Soluble Guanylate Cyclase (sGC) Stimulator — PAH / CTEPH
Pregnancy: Contraindicated — teratogenic; mandatory pregnancy prevention programme
Riociguat
Brand names: Adempas
Adult dose
Dose: 1 mg 3 times daily initially; increase by 0.5 mg TDS every 2 weeks to maximum tolerated dose
Route: Oral
Frequency: 3 times daily
Max: 2.5 mg 3 times daily (7.5 mg/day total)
Unique mechanism: stimulates sGC directly AND enhances sGC sensitivity to nitric oxide — increases cGMP. Only drug licensed for both PAH AND inoperable/post-surgical CTEPH (chronic thromboembolic pulmonary hypertension). Mandatory REMS programme. Titrate based on systolic BP — reduce/hold if SBP <95 mmHg.
Paediatric dose
Route:
Seek specialist opinion — not licensed in paediatrics
Dose adjustments
Renal
CrCl <15 mL/min: insufficient data — not recommended; CrCl 15–80: use with caution
Hepatic
Child-Pugh C: contraindicated; Child-Pugh B: use with caution
Clinical pearls
- Only drug approved for both PAH and CTEPH — dual indication is clinically unique; mechanism: stimulates sGC both NO-dependently and NO-independently
- PATENT-1 (PAH) and CHEST-1 (CTEPH) trials established efficacy
- CTEPH: pulmonary endarterectomy (PEA) is curative if operable — riociguat is for inoperable or persistent post-PEA CTEPH; balloon pulmonary angioplasty (BPA) also an option
- Absolute contraindication with PDE5 inhibitors (both enhance cGMP) — switching requires washout
- Titrate over 8 weeks to maximum tolerated dose — monitor BP at each visit
Contraindications
- Concurrent nitrates or nitric oxide donors (absolute — hypotension)
- Concurrent PDE5 inhibitors (sildenafil, tadalafil, vardenafil — absolute)
- Concurrent non-specific PDE inhibitors
- Pregnancy
- SBP <95 mmHg at initiation
- Pulmonary veno-occlusive disease
Side effects
- Hypotension
- Headache
- Dizziness
- Dyspepsia
- Nausea/vomiting
- Diarrhoea
- Peripheral oedema
- Haemoptysis (in CTEPH — monitor)
Interactions
- PDE5 inhibitors — absolute contraindication (synergistic cGMP increase → severe hypotension)
- Nitrates/NO donors — absolute contraindication
- Strong CYP3A4/P-gp inhibitors (ketoconazole, ritonavir) — increase riociguat levels — start at 0.5 mg TDS
- Antacids — reduce absorption (separate by 1 hour)
Monitoring
- Blood pressure (systolic) at each visit
- 6MWD and echocardiography/RHC
- Haemoptysis (CTEPH patients)
- Renal function and LFTs
- Pregnancy test monthly
Reference: BNFc; BNF 90; PATENT-1 Trial; CHEST-1 Trial; NICE TA401 (Riociguat for PAH and CTEPH); ESC/ERS PAH Guidelines 2022. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.