Source: FDA, National Drug Code (US) Revision Year: 2020
Noxivent is contraindicated in neonates dependent on right-to-left shunting of blood.
Wean from Noxivent [see Dosage and Administration (2.2)]. Abrupt discontinuation of Noxivent may lead to worsening oxygenation and increasing pulmonary artery pressure, i.e., Rebound Pulmonary Hypertension Syndrome. Signs and symptoms of Rebound Pulmonary Hypertension Syndrome include hypoxemia, systemic hypotension, bradycardia, and decreased cardiac output. If Rebound Pulmonary Hypertension occurs, reinstate Noxivent therapy immediately.
Nitric oxide combines with hemoglobin to form methemoglobin, which does not transport oxygen. Methemoglobin levels increase with the dose of Noxivent; it can take 8 hours or more before steady-state methemoglobin levels are attained. Monitor methemoglobin and adjust the dose of Noxivent to optimize oxygenation.
If methemoglobin levels do not resolve with decrease in dose or discontinuation of Noxivent, additional therapy may be warranted to treat methemoglobinemia [see Overdosage (10)].
Nitrogen dioxide (NO2) forms in gas mixtures containing NO and O2. Nitrogen dioxide may cause airway inflammation and damage to lung tissues. If there is an unexpected change in NO2 concentration, or if the NO2 concentration reaches 3 ppm when measured in the breathing circuit, then the delivery system should be assessed in accordance with the NOxBOXi and NOxMixer Technical Guide troubleshooting section, and the NO2 analyzer should be recalibrated. The dose of Noxivent and/or FiO2 should be adjusted as appropriate.
Patients with left ventricular dysfunction treated with Noxivent may experience pulmonary edema, increased pulmonary capillary wedge pressure, worsening of left ventricular dysfunction, systemic hypotension, bradycardia and cardiac arrest. Discontinue Noxivent while providing symptomatic care.
The following adverse reactions are discussed elsewhere in the label:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from the clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Controlled studies have included 325 patients on nitric oxide doses of 5 to 80 ppm and 251 patients on placebo. Total mortality in the pooled trials was 11% on placebo and 9% on nitric oxide, a result adequate to exclude nitric oxide mortality being more than 40% worse than placebo. In both the NINOS and CINRGI studies, the duration of hospitalization was similar in nitric oxide and placebo-treated groups.
From all controlled studies, at least 6 months of follow-up is available for 278 patients who received nitric oxide and 212 patients who received placebo. Among these patients, there was no evidence of an adverse effect of treatment on the need for rehospitalization, special medical services, pulmonary disease, or neurological sequelae. In the NINOS study, treatment groups were similar with respect to the incidence and severity of intracranial hemorrhage, Grade IV hemorrhage, periventricular leukomalacia, cerebral infarction, seizures requiring anticonvulsant therapy, pulmonary hemorrhage, or gastrointestinal hemorrhage. In CINRGI, the only adverse reaction (>2% higher incidence on nitric oxide than on placebo) was hypotension (14% vs. 11%).
Post marketing reports of accidental exposure to nitric oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache.
Nitric oxide donor agents such as prilocaine, sodium nitroprusside and nitroglycerine may increase the risk of developing methemoglobinemia.
Animal reproduction studies have not been conducted with Noxivent. It is not known if Noxivent can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Noxivent is not indicated for use in adults.
Nitric oxide is not indicated for use in the adult population, including nursing mothers. It is not known whether nitric oxide is excreted in human milk.
The safety and efficacy of nitric oxide for inhalation has been demonstrated in term and near-term neonates with hypoxic respiratory failure associated with evidence of pulmonary hypertension [see Clinical Studies (14.1)]. Additional studies conducted in premature neonates for the prevention of bronchopulmonary dysplasia have not demonstrated substantial evidence of efficacy [see Clinical Studies (14.3)]. No information about its effectiveness in other age populations is available.
Nitric oxide is not indicated for use in the adult population.
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