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Soluble Guanylate Cyclase Stimulator — PAH / CTEPH Pregnancy: ABSOLUTE CONTRAINDICATION — teratogenic; mandatory Pregnancy Prevention Programme

Riociguat

Brand names: Adempas

Adult dose

Dose: Start 1 mg three times daily; uptitrate by 0.5 mg every 2 weeks to maximum 2.5 mg three times daily (if systolic BP ≥95 mmHg and no hypotension symptoms)
Route: Oral
Frequency: Three times daily (approximately 6–8 hours apart)
Max: 2.5 mg three times daily
Soluble guanylate cyclase (sGC) stimulator for: (1) PAH (WHO Group 1) — WHO functional class II–III; (2) Chronic thromboembolic pulmonary hypertension (CTEPH — WHO Group 4) — inoperable or residual/recurrent after pulmonary endarterectomy. Unique indication for CTEPH (no other oral drug approved for CTEPH).

Paediatric dose

Dose: Seek specialist opinion mg/kg
Route: Oral
Frequency: Three times daily
Max: Not established in children
Not licensed in children — seek specialist paediatric cardiology/respiratory opinion

Dose adjustments

Renal

Use with caution if eGFR <30 mL/min/1.73m²; limited data

Hepatic

Avoid in severe hepatic impairment (Child-Pugh C)

Paediatric weight-based calculator

Not licensed in children — seek specialist paediatric cardiology/respiratory opinion

Clinical pearls

  • Only oral drug approved for CTEPH — CHEST-1 trial: riociguat improved 6MWD by 46 metres and reduced pulmonary vascular resistance in inoperable CTEPH
  • PATENT-1 trial (PAH): riociguat significantly improved 6MWD and time to clinical worsening — approved as alternative to PDE5 inhibitors in PAH
  • PDE5 inhibitor interaction is ABSOLUTE — both riociguat and sildenafil/tadalafil increase cGMP; combination causes severe life-threatening hypotension; this combination has caused deaths
  • Titration schedule: uptitrate by 0.5 mg every 2 weeks ONLY if systolic BP ≥95 mmHg and no hypotension symptoms — do not rush titration
  • CTEPH: surgical pulmonary endarterectomy is the curative treatment for operable CTEPH — riociguat for inoperable disease or residual/recurrent PH post-surgery
  • Pregnancy Prevention Programme mandatory — teratogenic; two forms of contraception required; monthly pregnancy test

Contraindications

  • Concomitant PDE5 inhibitors (sildenafil, tadalafil — ABSOLUTE CONTRAINDICATION)
  • Concomitant nitrates
  • Pregnancy — ABSOLUTE CONTRAINDICATION
  • Severe hypotension

Side effects

  • Hypotension (most important — titrate carefully)
  • Headache
  • Dyspepsia
  • Diarrhoea
  • Nausea
  • Peripheral oedema
  • Haemoptysis

Interactions

  • PDE5 inhibitors — ABSOLUTE CONTRAINDICATION (sildenafil, tadalafil, vardenafil — additive hypotension)
  • Nitrates — absolute contraindication
  • Strong CYP3A4/P-gp inhibitors (azoles, HIV protease inhibitors) — increase riociguat levels; start at 0.5 mg TDS
  • Antacids — reduce absorption (separate by 1 hour)

Monitoring

  • Blood pressure (at each dose uptitration)
  • 6MWD and NT-proBNP
  • Right heart catheterisation
  • Haemoptysis (pulmonary vascular disease risk)
  • Pregnancy test monthly

Reference: BNFc; BNF 90; CHEST-1 Trial (Ghofrani et al. NEJM 2013); PATENT-1 Trial (Ghofrani et al. NEJM 2013); ESC/ERS PAH Guidelines 2022; NICE TA401; SPC Adempas. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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