AdultPediatricOrphan Designations Acute respiratory distress syndrome in adults Cystic fibrosis Pulmonary arterial hypertension Sickle cell crisis: For acute treatment of sickle cell vaso-occlusive crisis (pain crises) Diagnosis of sarcoidosis Idiopathic pulmonary fibrosis Nontuberculosis mycobacterial infections Sponsors INO Therapeutics, Inc; Perryville III Corporate Park, 53 Frontage RD, 3rd Floor; Hampton, NJ 08827 GeNo, LLC; 2941 Oxbow Circle; Cocoa, Florida 32926 Advanced Inhalation Therapies Ltd; 2 Ilan Ramon Street; Ness Ziona, Israel Dosage Forms & Strengths inhalation gas 100ppm 800ppm Hypoxic Respiratory Failure Indicated in term and near-term neonates with hypoxic respiratory failure associated with evidence of pulmonary hypertension Additional studies conducted in premature neonates for the prevention of bronchopulmonary dysplasia have not demonstrated substantial evidence of efficacy Term and near-term neonates (>34 weeks gestation): 20 ppm, inhaled for up to 14 days Decrease dose gradually at end of treatment, do not discontinue abruptly Chronic Lung Disease Prevention (Orphan) Orphan designation to reduce the risk of chronic lung disease in premature neonates Orphan indication sponsor INO Therapeutics, Inc; Perryville III Corporate Park, 53 Frontage RD, 3rd Floor; Hampton, NJ 08827 Cystic Fibrosis (Orphan) Orphan designation for treatment of cystic fibrosis Orphan sponsor Novoteris, LLC; 7245 Garden Grove Blvd. Suite C; Garden Grove, CA 92841 >10% Hypotension (13%) Withdrawal (12%) 1-10% Atelectasis (9%) Hematuria (8%) Hyperglycemia (8%) Sepsis (7%) Infection (6%) Cellulitis (5%) Stridor (5%) Frequency Not Defined Intracranial hemorrhage, due to platelet aggregation inhibition Seizure Gastrointestinal hemorrhage due to platelet aggregation inhibition Methemoglobinemia Hematuria due to platelet aggregation inhibition Acute lung injury, atelectasis, hypoxemia, pulmonary edema, pulmonary hemorrhage, pulmonary toxicity due to nitrogen dioxide formation Postmarketing Reports Accidental exposure to nitric oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache Contraindications Hypersensitivity Neonates dependent on right-to-left shunting of blood Cautions Methemoglobinemia and NO2 levels are dose dependent; the most common adverse reaction is hypotension Closely monitor PaO2 and methemoglobin levels; measure methemoglobin levels within 4-8 hr after initiation of treatment and then periodically throughout treatment Monitor NO2 levels continuously with a suitable nitric oxide delivery system If methemoglobin levels are elevated and do not resolve with decreased dose or discontinuation, additional therapy may be warranted (eg, IV vitamin C, IV methylene blue, blood transfusion); hypoxemia from methemoglobinemia may occur Wean gradually to avoid rebound pulmonary hypertension syndrome; symptoms include worsening oxygenation, increased pulmonary artery pressure (PAP), systemic hypotension, and decreased cardiac output; reinstate nitric oxide immediately Nitrogen dioxide (NO2) forms in gas mixtures containing NO and O2 and may cause airway inflammation and damage to lung tissues; if NO2 exceeds 0.5 ppm, decrease the dose of nitric oxide If there is unexpected change in NO2 concentration, or if NO2 concentration reaches 3 ppm when measured in breathing circuit, assess delivery system; may need to adjust dose as appropriate Patients with left ventricular dysfunction may experience pulmonary edema when treated with nitric oxide, increased pulmonary capillary wedge pressure, worsening of left ventricular dysfunction, systemic hypotension, bradycardia, and cardiac arrest Drug interaction overview Nitric oxide donor agents such as prilocaine, sodium nitroprusside and nitroglycerine may increase risk of developing methemoglobinemia Pregnancy Limited data available; risk of adverse outcomes increased in pregnant patients with pulmonary arterial hypertension; inhaled nitric oxide may be used to improve pulmonary blood flow and oxygenation in pregnant patients with pulmonary hypertension who also have cardiac decompensation Lactation Nitric oxide and metabolites are endogenous to breast milkPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Relaxes vascular smooth muscle, resulting in pulmonary vasodilation Combines with oxyhemoglobin to produce methemoglobin & nitrate Excretion Nitrate excreted quickly, renal Ventilator Administration Validated ventilatory systems Must be adminstered using a calibrated and validated nitric oxide delivery system by trained personnel for the particular brand (eg, INOmax, Genosyl) Keep available a back up battery power supply and an independent reserve nitric oxide delivery system to address power and system failures INOmax Consult the delivery system label or call 877-566-9466 or visit inomax.com for a current list of validated systems Genosyl Consult the Delivery system operator’s manual or call 1-877-337-4118 or visit www.vero-biotech.com Monitoring Measure methemoglobin within 4-8 hr after initiating and periodically throughout treatment Monitor for PaO2 and inspired NO2 during administration Weaning and discontinuation Avoid abrupt discontinuation; wean gradually To wean, downtitrate in several steps, pausing several hours at each step to monitor for hypoxemia No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. 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