Tapering Riociguat (Adempas) When Switching to Opsynvi
When switching from Adempas (riociguat) and Opsumit (macitentan) to Opsynvi (combination of macitentan and riociguat), a gradual stepwise tapering of Adempas should be performed while maintaining the Opsumit dose until Opsynvi is initiated.
Recommended Tapering Protocol for Riociguat
- Begin tapering riociguat by reducing the dose by approximately 33% of the original dose, and maintain this reduced dose for 2 weeks 1
- After 2 weeks, if the patient remains clinically stable, further reduce the dose to 50% of the original dose for another 2 weeks 1
- For the final step before discontinuation, administer the lowest possible dose (0.5 mg) every other day for 1 week 1
- Start Opsynvi immediately after completing the riociguat taper while continuing Opsumit without interruption until the day of Opsynvi initiation 2
Rationale for Gradual Tapering
- Slow tapering should be performed to minimize adverse effects and maintain clinical stability during the transition 1
- Stepwise tapering has been shown to be more effective than single-step or abrupt discontinuation in minimizing withdrawal symptoms across multiple drug classes 1
- The pharmacokinetic interaction between macitentan and riociguat has been studied, showing no significant drug-drug interactions that would affect the safety of the transition 2
Monitoring During Tapering
- Monitor for clinical deterioration after each dose reduction before proceeding to the next step 1
- If signs of clinical worsening occur (increased dyspnea, decreased exercise capacity, or worsening functional class), return to the previous well-tolerated dose and slow the taper further 1
- Pay particular attention to hemodynamic parameters if available, as they provide objective measures of treatment response 3
Special Considerations
- For patients who have been on high doses of riociguat (2.5 mg TID), consider a more gradual taper with additional intermediate steps 1
- Patients with high-risk features or previous instability may require more cautious tapering with smaller incremental reductions 1
- Ensure there is no gap in therapy between the last dose of individual components and initiation of Opsynvi 2, 3
Potential Pitfalls to Avoid
- Avoid abrupt discontinuation of riociguat as this may lead to clinical deterioration 1
- Do not taper Opsumit (macitentan) since this component will be continued in Opsynvi 2, 3
- Avoid prolonged overlap between individual components and Opsynvi to prevent excessive dosing 2
- Be aware that some patients may require adjustment of the Opsynvi dose if they experience side effects during the transition 3