INOmax

What it is

INOmax is nitric oxide administered by inhalation. Nitric oxide, the active substance in INOmax, is a pulmonary vasodilator. INOmax is a gaseous blend of nitric oxide and nitrogen (0.08% and 99.92%, respectively for 800 ppm). INOmax 4,880 is a gaseous blend of nitric oxide (0.488%) and nitrogen (99.512%).

Approved indications

— Treatment of term and near-term (>34 weeks) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension, to improve oxygenation and to reduce the need for extracorporeal membrane oxygenation. — Selective decrease of pulmonary arterial pressure in patients with perioperative pulmonary hypertension in conjunction with heart surgery.

Dosing overview

The maximum recommended dose of INOmax is 20 ppm. In key clinical trials, the starting dose was 20 ppm. Starting as soon as possible and within 4-24 hours of therapy, the dose should be weaned to 5 ppm provided that arterial oxygenation is adequate at this lower dose. Inhaled nitric oxide therapy should be maintained at 5 ppm until there is improvement in the neonate's oxygenation such that the FiO2 (fraction of inspired oxygen) < 0.60. Treatment can be maintained up to 96 hours or until the underlying oxygen desaturation has resolved and the neonate is ready to be weaned from INOmax therapy. The duration of therapy is variable, but typically less than four days. For paediatric use in cardiac surgery (ages 0-17 years), the starting dose of inhaled nitric oxide is 10 ppm of inhaled gas. The dose may be increased up to 20 ppm if the lower dose has not provided sufficient clinical effects. The dose range for adult patients with pulmonary hypertension in the context of cardiac surgery is 10–20 ppm of inhaled nitric oxide. The lowest effective dose should be administered, and the dose should be weaned down to 5 ppm provided that the clinical effect remains adequate at this lower dose.

Key safety warnings

The INOmax dose should not be discontinued abruptly as it may result in rebound pulmonary hypertension syndrome, characterised by an increase in pulmonary artery pressure and/or worsening of blood oxygenation. Signs and symptoms include hypoxaemia, systemic hypotension, bradycardia and decreased cardiac output. Weaning from inhaled nitric oxide should be performed with caution. For patients transported to other facilities for additional treatment who need to continue with inhaled nitric oxide, arrangements should be made to ensure the continuous supply of inhaled nitric oxide during transportation. The physician should have access at the bedside to a reserve nitric oxide delivery system. A large portion of nitric oxide for inhalation is absorbed systemically. The end products of nitric oxide that enter the systemic circulation are predominantly methaemoglobin and nitrate. The concentrations of methaemoglobin in the blood should be measured within one hour after initiation of INOmax therapy, using an analyser which can reliably distinguish between foetal haemoglobin and methaemoglobin. If it is > 2.5% the INOmax dose should be decreased and the administration of reducing agents may be considered. NO2 rapidly forms in gas mixtures containing nitric oxide and O2, and nitric oxide may in this way cause airway inflammation and damage. The dose of nitric oxide should be reduced if the concentration of nitrogen dioxide exceeds 0.5 ppm. In a diagnostic study of pulmonary vasoreactivity in children, some patients who had pre-existing left ventricular dysfunction, treated with nitric oxide, even for short durations, experienced an increased rate of serious adverse events including pulmonary oedema, worsening of left ventricular dysfunction, systemic hypotension, bradycardia and cardiac arrest. The benefit/risk of using inhaled nitric oxide in patients with clinically significant left ventricular dysfunction should be evaluated on a case-by-case basis. Consider reducing left ventricular afterload to minimize the occurrence of pulmonary oedema.

Contraindications

Neonates known to be dependent on right-to-left or significant left-to-right shunting of blood are contraindicated. Hypersensitivity to the active substance or any of the excipients is also contraindicated.

Regulatory history

INOmax nitric oxide 800 ppm was first listed on the ARTG on 22 November 2007. On 27 July 2015, the TGA approved a major variation for INOmax, extending its indication for the treatment of peri- and post-operative pulmonary hypertension in paediatric patients (ages 0-17 years) undergoing heart surgery. INOmax nitric oxide 4,880 ppm was first listed on the ARTG on 27 January 2026.