NEODOSE

INDICATIONS

Persistent pulmonary hypertension (PPHN), adjunct: The Food and Drug Administration recommends against the use, particularly chronic use, of sildenafil in children due to an observation of increased mortality with increased doses in a long-term, pediatric, clinical trial. However, there may be situations when benefit outweighs risk . Adjunctive sildenafil may be used in infants with PPHN who are refractory to inhaled nitric oxide, particularly when the oxygenation index is greater than 25. Use limited to treatment of patients with PPHN refractory to inhaled nitric oxide (iNO) and other conventional therapies, those who are persistently unable to be weaned off of inhaled nitric oxide, or in situations where nitric oxide and high frequency ventilation are not available. According to an intervention review of the use of sildenafil in neonates with PPHN, sildenafil was associated with a significant reduction in mortality with a number need to treat to benefit of 3. All studies included in the review were in resource-limited settings . In a prospective, randomized trial (n=65), oral sildenafil was more effective than magnesium sulfate in a setting without iNO or high frequency ventilation based on time to adequate effect, duration of mechanical ventilation, and use of inotropic support . Sildenafil has been reported to improve pulmonary blood flow in patients with severe Ebstein’s anomaly. A retrospective study (n=7) reported reductions in pulmonary hypertension, and improved respiratory status and oxygenation in neonates with congenital diaphragmatic hernia (CDH) with pulmonary hypertension refractory to inhaled nitric oxide.

CONTRAINDICATIONS

• Contraindicated in patients taking organic nitrates in any form and in patients with a known hypersensitivity to sildenafil

PRECAUTIONS:

• Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported ; increased risk with crowded optic disc, hypertension, coronary artery disease, hyperlipidemia, or smoking
• Bleeding events have been reported in postmarketing surveillance, though a causal relationship has not been established. Hypersensitivity reactions, including rash and urticaria, have occurred with sildenafil therapy. An increased mortality with increased doses in a long-term, pediatric, clinical trial has been observed.

ADVERSE EFFECTS

Use in neonates should be restricted and considered experimental. Data in neonates remain limited. The most concerning short-term adverse effects are worsening oxygenation and systemic hypotension. There is one case report of bleeding after circumcision in a neonate receiving chronic therapy . Use with caution in infants with sepsis. Sildenafil causes transient impairment of color discrimination in adults, and there is concern that it could increase the risk of severe retinopathy of prematurity if used in extremely premature infants. In a study of neonates receiving sildenafil for at least weeks (n=22), positive ocular findings were reported in 4 patients, none of which were considered drug-related . Sildenafil did not increase the risk of retinopathy of prematurity (odds ratio 1.35 (95% CI, 0.39 to 4.62; p=0.63)) in a case-control study (n=68) of premature infants born before 30 weeks gestation. One infant each in the sildenafil group and control group required laser treatment .

ADMINISTRATION

Available as 0.8 mg/mL IV solution. Infuse the loading dose over 3 hours.

MONITORING

Continuous monitoring of blood pressure and oxygenation