Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Inadequate response
If it is judged that clinical response is inadequate at 4-6 hours after starting Mixture NO 800 ppm in Nitrogen, the following should be considered.
For patients who are to be referred to another hospital, to prevent worsening of their condition on acute discontinuation of Mixture NO 800 ppm in Nitrogen, the availability of nitric oxide during transport should be assured.
Rescue, such as Extra Corporeal Membrane Oxygenation (ECMO) where available, should be considered based on continued deterioration or failure to improve, defined by criteria based on local circumstances.
Special patient populations
In clinical trials, no efficacy has been demonstrated with the use of inhaled nitric oxide in patients with congenital diaphragmatic hernia.
Treatment with inhaled nitric oxide might aggravate cardiac insufficiency in a situation with left-toright shunting.
This is due to unwanted pulmonary vasodilation caused by inhaled nitric oxide, resulting in a further increase of already existing pulmonary hyperperfusion thus potentially giving raise to forward or backward failure. It, therefore, is recommended that prior to the administration of nitric oxide, pulmonary artery catheterisation or echocardiographic examination of central haemodynamics be performed. Inhaled nitric oxide should be used with caution in patients with complex heart defect, where high pressure in the pulmonary artery is of importance for maintaining circulation.
Inhaled nitric oxide should also be used with caution in patients with compromised left ventricular function and elevated baseline pulmonary capillary pressure (PCWP) as they may be at an increased risk of developing cardiac failure (e.g. pulmonary oedema).

Discontinuation of therapy
The Mixture NO dose should not be discontinued abruptly as it may result in an increase in pulmonary artery pressure (PAP) and/or worsening of blood oxygenation (PaO2). Deterioration in oxygenation and elevation in PAP may also occur in neonates with no apparent response to Mixture NO 800 ppm in Nitrogen. 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.

Formation of methaemoglobin
A large portion of nitric oxide for inhalation is absorbed systemically. The end medicinal products of nitric oxide that enter the systemic circulation are predominantly methaemoglobin and nitrate. The concentrations of methaemoglobin in the blood should be monitored, see section 4.2.

Formation of NO2
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.

Effects on platelets
Animal models have shown that nitric oxide may interact with haemostasis, resulting in an increased bleeding time. Data in adult humans are conflicting, and there has been no increase in bleeding complications in randomised controlled trials in term and near-term neonates with hypoxic respiratory failure.
Regular monitoring of haemostasis and measurement of bleeding time is recommended during the administration of Mixture NO 800 ppm in Nitrogen for more than 24 hours to patients with functional or quantitative platelet anomalies, a low coagulation factor or receiving anticoagulation treatment.

Effects on Driving

4.7 Effects on ability to drive and use machines

Not relevant.