Nitric Oxide

Nitric Oxide or Nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals including humans and is an extremely important intermediate in the chemical industry. It is also a toxic air pollutant produced by automobile engines and power plants. Nitric Oxide (NO) should not be confused with nitrous oxide (N2O), a general anaesthetic, or with nitrogen dioxide (NO2) which is another poisonous air pollutant. The Nitric Oxide molecule is a free radical, which is relevant to understanding its high reactivity. It reacts with the ozone in air to form nitrogen dioxide, signalled by the appearance of the reddish-brown color.

Nitric Oxide® 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.

Nitric Oxide is a gas that is inhaled. It works by relaxing smooth muscle to widen (dilate) blood vessels, especially in the lungs.

Nitric Oxide is used together with a breathing machine (ventilator) to treat respiratory failure in premature babies.

Your baby will receive this medication in a neonatal intensive care unit (NICU) or similar hospital setting.

Nitric Oxide may also be used for purposes not listed in this medication guide.

Dosage

Term and Near-Term Neonates with Hypoxic Respiratory Failure

The recommended dose of Nitric Oxide 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 Nitric Oxide therapy.

Doses greater than 20 ppm are not recommended.

Administration

Training in Administration

The user of Nitric Oxide and Nitric Oxide Delivery Systems must satisfactorily complete a comprehensive periodic training program for health care professionals provided by the delivery system and drug manufacturers. Health professional staff that administers Nitric Oxide therapy have access to supplier-provided 24 hour/365 days per year technical support on the delivery and administration of Nitric Oxide at 1-877-566-9466.

Nitric Oxide Delivery Systems

Nitric Oxide must be administered using a calibrated Nitric Oxide DSIR ® Nitric Oxide Delivery System. Only validated ventilator systems should be used in conjunction with Nitric Oxide. Consult the Nitric Oxide Delivery System label or call 877.566.9466/visit Nitric Oxide.com for a current list of validated systems.

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 Nitric Oxide and periodically throughout treatment.

Monitor for PaO2 and inspired NO2 during Nitric Oxide administration.

Weaning and Discontinuation

Avoid abrupt discontinuation of Nitric Oxide. To wean Nitric Oxide, downtitrate in several steps, pausing several hours at each step to monitor for hypoxemia.

How supplied

Dosage Forms And Strengths

Nitric Oxide (Nitric Oxide) gas is available in an 800 ppm concentration.

Storage And Handling

Nitric Oxide (Nitric Oxide) is available in the following sizes:

Store at 25°C (77°F) with excursions permitted between 15–30°C (59–86°F).

All regulations concerning handling of pressure vessels must be followed.

Protect the cylinders from shocks, falls, oxidizing and flammable materials, moisture, and sources of heat or ignition.

Occupational Exposure

The exposure limit set by the Occupational Safety and Health Administration (OSHA) for Nitric Oxide is 25 ppm, and for NO2 the limit is 5 ppm.

Distributed by INO Therapeutics LLC 675 McDonnell Blvd. Hazelwood, MO 63042, USA. Revised: Oct 2015

See also:
What is the most important information I should know about Nitric Oxide?

Your baby will receive this medication in a neonatal intensive care unit (NICU) or similar hospital setting.

Nitric Oxide is inhaled into the baby's lungs through the mouth or nose. Your baby may also be using a breathing tube connected to a ventilator (a machine that moves air in and out of the lungs to help your baby breathe easier and get enough oxygen).

Your baby will remain under constant supervision during treatment with Nitric Oxide.

See also:
What other drugs will affect Nitric Oxide?

No formal drug-interaction studies have been performed, and a clinically significant interaction with other medications used in the treatment of hypoxic respiratory failure cannot be excluded based on the available data. Nitric Oxide has been administered with tolazoline, dopamine, dobutamine, steroids, surfactant, and high-frequency ventilation. Although there are no study data to evaluate the possibility, Nitric Oxide donor compounds, including sodium nitroprusside and nitroglycerin, may have an additive effect with Nitric Oxide on the risk of developing methemoglobinemia. An association between prilocaine and an increased risk of methaemoglobinaemia, particularly in infants, has specifically been described in a literature case report. This risk is present whether the drugs are administered as oral, parenteral, or topical formulations.

See also:
What are the possible side effects of Nitric Oxide?

The following adverse reactions are discussed elsewhere in the label;

Hypoxemia

Worsening Heart Failure

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from the clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Controlled studies have included 325 patients on Nitric Oxide doses of 5 to 80 ppm and 251 patients on placebo. Total mortality in the pooled trials was 11% on placebo and 9% on Nitric Oxide gas for inhalation, a result adequate to exclude Nitric Oxide mortality being more than 40% worse than placebo.

In both the NINOS and CINRGI studies, the duration of hospitalization was similar in Nitric Oxide gas for inhalation and placebo-treated groups.

From all controlled studies, at least 6 months of follow-up is available for 278 patients who received Nitric Oxide gas and 212 patients who received placebo. Among these patients, there was no evidence of an adverse effect of treatment on the need for re-hospitalization, special medical services, pulmonary disease, and neurological sequelae.

In the NINOS study, treatment groups were similar with respect to the incidence and severity of intracranial hemorrhage, Grade IV hemorrhage, periventricular leukomalacia, cerebral infarction, seizures requiring anticonvulsant therapy, pulmonary hemorrhage, or gastrointestinal hemorrhage.

In CINRGI, the only adverse reaction (>2% higher incidence on Nitric Oxide gas for inhalation than on placebo) was hypotension (14% vs. 11%).

Postmarketing Experience

Post marketing reports of accidental exposure to Nitric Oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache.