NITRIC Drug Interactions: What You Need to Know

DRUG INTERACTIONS Nitric oxide donor compounds may increase the risk of developing methemoglobinemia ( 7 ). Revised: 08/2023

7. DRUG INTERACTIONS

7.1 Nitric Oxide Donor Agents Nitric oxide donor agents such as prilocaine, sodium nitroprusside and nitroglycerine may increase the risk of developing methemoglobinemia.

CONTRAINDICATIONS Neonates dependent on right-to-left shunting of blood ( 4 ).

4.

Contraindications

Noxivent™ is contraindicated in neonates dependent on right-to-left shunting of blood.

WARNINGS AND PRECAUTIONS Rebound: Abrupt discontinuation of Noxivent™ may lead to worsening oxygenation and increasing pulmonary artery pressure ( 5.1 ). Methemoglobinemia: Methemoglobin increases with the dose of nitric oxide; following discontinuation or reduction of nitric oxide, methemoglobin levels return to baseline over a period of hours ( 5.2 ). Elevated NO 2 Levels: Monitor NO 2 levels ( 5.3 ).

Heart

Failure: In patients with pre-existing left ventricular dysfunction, Noxivent™ may increase pulmonary capillary wedge pressure leading to pulmonary edema ( 5.4 ).

5. WARNINGS AND PRECAUTIONS

5.1 Rebound Pulmonary Hypertension Syndrome following Abrupt Discontinuation Wean from Noxivent™ <span class="opacity-50 text-xs">[see Dosage and Administration (2.2 )]</span>. Abrupt discontinuation of Noxivent™ may lead to worsening oxygenation and increasing pulmonary artery pressure, i.e., Rebound Pulmonary Hypertension Syndrome. Signs and symptoms of Rebound Pulmonary Hypertension Syndrome include hypoxemia, systemic hypotension, bradycardia, and decreased cardiac output.

If Rebound Pulmonary

Hypertension occurs, reinstate Noxivent™ therapy immediately.

5.2 Hypoxemia from Methemoglobinemia Nitric oxide combines with hemoglobin to form methemoglobin, which does not transport oxygen. Methemoglobin levels increase with the dose of Noxivent™; it can take 8 hours or more before steady-state methemoglobin levels are attained. Monitor methemoglobin and adjust the dose of Noxivent™ to optimize oxygenation. If methemoglobin levels do not resolve with decrease in dose or discontinuation of Noxivent™, additional therapy may be warranted to treat methemoglobinemia <span class="opacity-50 text-xs">[see Overdosage (10 )]</span>.

5.3 Airway Injury from Nitrogen Dioxide Nitrogen dioxide (NO 2 ) forms in gas mixtures containing NO and O 2 . Nitrogen dioxide may cause airway inflammation and damage to lung tissues. If there is an unexpected change in NO 2 concentration, or if the NO 2 concentration reaches 3 ppm when measured in the breathing circuit, then the delivery system should be assessed in accordance with the Nitric Oxide Delivery System O&amp;M Manual troubleshooting section, and the NO 2 analyzer should be recalibrated. The dose of Noxivent™ and/or FiO 2 should be adjusted as appropriate.

5.4 Worsening Heart Failure Patients with left ventricular dysfunction treated with Noxivent™ may experience pulmonary edema, increased pulmonary capillary wedge pressure, worsening of left ventricular dysfunction, systemic hypotension, bradycardia and cardiac arrest.

Discontinue

Noxivent™ while providing symptomatic care.