Drug Interactions between nitric oxide and sildenafil

GENERALLY AVOID: Concurrent use of sildenafil with nitric oxide may result in hypotension due to additive vasodilatory effects. The combination of inhaled nitric oxide (iNO) with oral or intravenous sildenafil has been used investigationally for the treatment of pulmonary hypertension, often during and/or after surgery. Clinical data are limited and conflicting. Beneficial effects on pulmonary arterial pressure and pulmonary vascular resistance have been reported in adults. For example, a study in cardiac surgery patients (n=20) with postcapillary out-of-proportion pulmonary hypertension due to left ventricular dysfunction found that postoperative coadministration of iNO and oral sildenafil was safe. This combination also had an additive favorable effect on pulmonary arterial pressure and pulmonary vascular resistance, without systemic hypotension and ventilation/perfusion mismatch. A retrospective study in 7 pediatric patients who failed postoperative weaning of iNO after congenital cardiac surgery demonstrated that oral sildenafil may facilitate withdrawal of iNO and prevent rebound pulmonary hypertension in these types of patients. However, a study in ventilated infants (n=15) post ventricular or atrioventricular septal defect surgery who received iNO and sildenafil, documented systemic hypotension as well as a worsening in arterial oxygenation and alveolar-arterial gradients.

MANAGEMENT: Due to the risk of potentially life-threatening hypotension, some authorities consider the concomitant use of sildenafil with nitrates in any form, including inhaled nitrates, to be contraindicated. If concurrent use is considered clinically necessary, close monitoring of hemodynamics, pulmonary function, and oxygenation is advisable in accordance with current local practice guidelines.