Criteria and Contraindications for Starting Riociguat in Pulmonary Hypertension
Riociguat is indicated for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA), and for patients with pulmonary arterial hypertension (PAH) WHO functional class II-III to improve exercise capacity and delay clinical worsening. 1, 2
Indications for Riociguat
For PAH Patients:
- Recommended for treatment-naive PAH patients with WHO functional class II symptoms who are not candidates for, or have failed, calcium channel blocker (CCB) therapy 3
- Recommended for treatment-naive PAH patients with WHO functional class III symptoms who are not candidates for, or have failed, CCB therapy 3
- Can improve 6-minute walking distance (6MWD), WHO functional class, delay time to clinical worsening, and improve cardiopulmonary hemodynamics 3, 4
For CTEPH Patients:
- Only approved targeted therapy for patients with inoperable CTEPH 1, 2
- Indicated for patients with persistent/recurrent CTEPH after PEA 1, 2
- Significantly increases 6MWD by 39 meters compared to placebo 1, 4
- Significantly reduces pulmonary vascular resistance (PVR) by 246 dyn.cm.s⁻⁵ compared to placebo 1, 4
Absolute Contraindications
- Concomitant use with phosphodiesterase-5 inhibitors (PDE5i) such as sildenafil, tadalafil, or vardenafil due to risk of severe hypotension 5, 6
- Pregnancy (Category X drug) 2
- Patients who are candidates for PEA surgery (surgery remains treatment of choice for operable CTEPH) 1
Relative Contraindications and Precautions
- Patients with systemic hypotension (SBP <95 mmHg) require careful dose titration 6, 7
- Caution in patients with hepatic or renal impairment (dose adjustments may be required) 6
- Caution in elderly patients (may have altered drug exposure) 6
- Smokers may require dose adjustments (smoking reduces riociguat exposure) 6
Dosing Considerations
- Requires dose titration based on systemic blood pressure response 3, 6
- Starting dose is typically lower with gradual titration to minimize risk of hypotension 6, 7
- Must be administered three times daily 2
- Patients should be monitored for hypotension during dose adjustment period 6, 7
Important Clinical Considerations
- All CTEPH patients should be evaluated by a multidisciplinary team including an experienced PEA surgeon to determine operability before considering riociguat 1
- Riociguat works through the nitric oxide pathway as a soluble guanylate cyclase stimulator, addressing pulmonary microvascular disease 1, 2
- Male patients treated with riociguat should be cautioned not to use PDE5 inhibitors for erectile dysfunction due to risk of severe hypotension 3
- Patients should be followed at specialized centers with at least one hemodynamic assessment 6-12 months after treatment initiation 1
- Most common adverse effects include headache, flushing, hypotension, and gastrointestinal disturbances 2, 6, 7
Transitioning from PDE5 Inhibitors
- Transitioning from PDE5i to riociguat requires a washout period to avoid dangerous hypotension 8, 6
- Relatively rapid transitioning from PDE5i to riociguat may be safe under careful observation for patients with inadequate clinical response to PDE5i 8
- An open-label study showed BNP significantly decreased by 116.5±188.6 pg/ml in patients transitioned from PDE5i to riociguat 8