INOMAX

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE INOmax ® is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents. INOmax is a vasodilator indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents. Dosage and administration 2 DOSAGE AND ADMINISTRATION The recommended dose is 20 ppm, maintained for up to 14 days or until the underlying oxygen desaturation has resolved ( 2.1 ). Doses greater than 20 ppm are not recommended ( 2.1 , 5.2 ) Administration: Avoid abrupt discontinuation ( 2.2 , 5.1 ). 2.1 Dosage Term and near-term neonates with hypoxic respiratory failure The recommended dose of INOmax is 20 ppm. Maintain treatment up to 14 days or until the underlying oxygen desaturation has resolved and the neonate is ready to be weaned from INOmax therapy. Doses greater than 20 ppm are not recommended [see Warnings and Precautions (5.2) ] . 2.2 Administration Nitric Oxide Delivery Systems INOmax must be administered using a calibrated, FDA-cleared Nitric Oxide Delivery System (NODS). There are various FDA-cleared NODS; refer to the NODS labeling to determine which NODS to use with this drug product and for needed information on training and technical support for users of this drug product with the NODS. When utilizing a nitric oxide delivery system specifically cleared for use in the MRI suite (e.g., the INOmax DSIR ® Plus MRI) only use INOmax MR conditional cylinders at 100 gauss or less [see How Supplied/Storage and Handling (16) ]. Keep available a backup battery power supply and an independent reserve nitric oxide delivery system to address power and system failures . Monitoring Measure methemoglobin within 4-8 hours after initiation of treatment with INOmax and periodically throughout treatment [see Warnings and Precautions (5.2) ] . Monitor for PaO 2 and inspired NO 2 during INOmax administration [see Warnings and Precautions (5.3) ] . Weaning and Discontinuation Avoid abrupt discontinuation of INOmax [see Warnings and Precautions (5.1) ]. To wean INOmax, downtitrate in several steps, pausing several hours at each step to monitor for hypoxemia. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Rebound: Abrupt discontinuation of INOmax may lead to worsening oxygenation and increasing pulmonary artery pressure ( 5.1 ). Methemoglobinemia: Methemoglobin increases with the dose of nitric oxide; following discontinuation or reduction of nitric oxide, methemoglobin levels return to baseline over a period of hours ( 5.2 ). Elevated NO 2 Levels: Monitor NO 2 levels ( 5.3 ). Heart Failure: In patients with pre-existing left ventricular dysfunction, INOmax may increase pulmonary capillary wedge pressure leading to pulmonary edema ( 5.4 ). 5.1 Rebound Pulmonary Hypertension Syndrome following Abrupt Discontinuation Wean from INOmax [see Dosage and Administration (2.2) ]. Abrupt discontinuation of INOmax 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 INOmax therapy immediately. 5.2 Hypoxemia from Methemoglobinemia Nitric oxide combines with hemoglobin to form methemoglobin, which does not transport oxygen. Methemoglobin levels increase with the dose of INOmax; it can take 8 hours or more before steady-state methemoglobin levels are attained. Monitor methemoglobin and adjust the dose of INOmax to optimize oxygenation. If methemoglobin levels do not resolve with decrease in dose or discontinuation of INOmax, additional therapy may be warranted to treat methemoglobinemia [see Overdosage (10) ]. 5.3 Airway Injury from Nitrogen Dioxide Nitrogen dioxide (NO 2 ) forms in gas mixtures containing NO and O 2 . Nitrogen dioxide may cause airway inflammation and damage to lung tissues. If there is an unexpected change in NO 2 concentration, or if the NO 2 concentration reaches 3 ppm when measured in the breathing circuit, then the delivery system should be assessed in accordance with the Nitric Oxide Delivery System O&M Manual troubleshooting section, and the NO 2 analyzer should be recalibrated. The dose of INOmax and/or FiO 2 should be adjusted as appropriate. 5.4 Worsening Heart Failure Patients with left ventricular dysfunction treated with INOmax may experience pulmonary edema, increased pulmonary capillary wedge pressure,