Dosing & Uses
Orphan 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
Adverse Effects
>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
Warnings
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
Pregnancy & Lactation
Pregnancy Category: C
Lactation: not known if excreted in breast milk
Pregnancy 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.Pharmacology
Mechanism of Action
Relaxes vascular smooth muscle, resulting in pulmonary vasodilation
Combines with oxyhemoglobin to produce methemoglobin & nitrate
Excretion
Nitrate excreted quickly, renal
Administration
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
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Formulary
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