Does Revatio (sildenafil) and selexipag cause hypotension?

Hypotensive Effects of Revatio (Sildenafil) and Selexipag

Yes, both Revatio (sildenafil) and selexipag can cause hypotension, with sildenafil having more pronounced systemic hemodynamic effects, while selexipag's hypotensive effect is generally milder. 1

Sildenafil (Revatio) and Hypotension

Mechanism and Hemodynamic Effects

• Sildenafil is a potent and highly specific phosphodiesterase type 5 (PDE-5) inhibitor that increases cGMP levels in vascular smooth muscle, leading to vasodilation 1
• Unlike inhaled nitric oxide which primarily affects the pulmonary vasculature, sildenafil has notable systemic hemodynamic effects 1
• Studies have shown that sildenafil:
  • Reduces mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR)
  • Increases cardiac index
  • Causes systemic vasodilation that can lead to hypotension 1

Clinical Implications

• Sildenafil increases sympathetically mediated vascular tone in humans, which may be a compensatory mechanism to offset vasodilation 2
• The risk of hypotension is significantly increased when sildenafil is combined with:
  • Nitrates (absolutely contraindicated due to potentially life-threatening hypotension) 3, 4
  • Other vasodilators 5
• In patients with pulmonary hypertension, the hypotensive effect is generally manageable but requires monitoring 1

Selexipag and Hypotension

Mechanism and Hemodynamic Effects

• Selexipag is an orally available, selective prostacyclin IP receptor agonist 1
• Although it has a similar mode of action to endogenous prostacyclin, selexipag has a different pharmacology and is chemically distinct 1
• Selexipag primarily reduces pulmonary vascular resistance with less pronounced effects on systemic blood pressure compared to other prostanoids 1

Clinical Evidence

• In a pilot randomized controlled trial in PAH patients, selexipag reduced PVR after 17 weeks without significant reports of severe hypotension 1
• In the large phase 3 GRIPHON trial with 1,156 patients, selexipag demonstrated efficacy in reducing morbidity and mortality without major hypotensive concerns 1

Comparative Hypotensive Risk

Sildenafil (Higher Risk)

• More likely to cause clinically significant hypotension, especially when combined with other vasodilators
• Has direct systemic vasodilatory effects
• May cause headache, flushing, and hypotension as common adverse events 3

Selexipag (Lower Risk)

• Generally produces less systemic hypotension than sildenafil
• More selective for the pulmonary circulation
• Hypotensive effects are typically milder and more manageable in clinical practice

Clinical Management Considerations

Monitoring Recommendations

• Monitor blood pressure regularly when initiating either medication
• More frequent monitoring is needed with sildenafil, especially during dose titration
• Be particularly vigilant in patients with:
  • Pre-existing hypotension
  • Hypovolemia
  • Severe left ventricular outflow obstruction
  • Autonomic dysfunction

Drug Interactions

• Avoid combining sildenafil with:
  • Nitrates (absolute contraindication)
  • Alpha-blockers (can cause significant hypotension) 3, 2
• Use caution when combining either drug with other antihypertensives

Dose Adjustments

• Consider lower starting doses in patients at risk for hypotension
• Titrate doses more slowly in elderly patients or those with hepatic impairment
• If hypotension occurs, temporary dose reduction may be necessary before attempting to re-escalate

In conclusion, while both medications can cause hypotension, sildenafil has more pronounced systemic effects and greater potential for clinically significant hypotension, particularly when combined with other vasodilators. Selexipag generally has a more favorable profile regarding systemic hypotension.