INOMAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INOMAX (INOMAX).
Inhaled nitric oxide acts as a selective pulmonary vasodilator by activating guanylate cyclase, increasing intracellular cyclic guanosine monophosphate (cGMP) in pulmonary vascular smooth muscle, leading to relaxation. It also reduces platelet aggregation and adhesion.
| Metabolism | Primarily metabolized in the pulmonary vasculature via rapid oxidation to nitrite and nitrate by reaction with oxygen and hemoglobin. Nitrate is excreted renally. |
| Excretion | Inhaled nitric oxide is rapidly inactivated by binding to hemoglobin to form methemoglobin and nitrate. Nitrate is excreted renally; approximately 70% of the dose appears as nitrate in the urine within 48 hours. Fecal excretion is minimal (<1%). |
| Half-life | Terminal elimination half-life of nitric oxide is minutes (2-6 seconds) due to rapid reaction with hemoglobin. The nitrate metabolite has a half-life of approximately 5 hours. Clinical context: The short half-life allows rapid titration of effect. |
| Protein binding | Nitric oxide is not significantly protein-bound. Its metabolite nitrate is minimally bound (<10%) to plasma proteins. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.2 L/kg (plasma volume). This reflects distribution primarily in the vascular space due to rapid inactivation. |
| Bioavailability | Inhaled: bioavailability is 100% for the pulmonary circulation; systemic bioavailability is negligible (<0.1%) due to rapid inactivation in blood. No other routes are clinically relevant. |
| Onset of Action | Inhalation: 1-3 minutes due to pulmonary vasodilation. Clinical effect (improved oxygenation) typically seen within 5-10 minutes. |
| Duration of Action | Duration of clinical effect is 3-5 minutes after discontinuation of inhalation due to rapid metabolism. Continuous administration is required to maintain effect. |
Inhaled: 20 ppm administered via inhalation. Initially, 20 ppm is recommended; adjust based on clinical response and oxygenation. Continuous administration.
| Dosage form | GAS |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Neonates and children: Inhaled dose of 20 ppm; same as adults. Use weight-based calculation for ventilator settings, but the concentration is fixed at 20 ppm. |
| Geriatric use | No specific dose adjustment in elderly patients; use same dosing as younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INOMAX (INOMAX).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Inhaled nitric oxide is rapidly inactivated in the bloodstream, making significant transfer unlikely. Caution advised. |
| Teratogenic Risk | INOMAX (inhaled nitric oxide) is not teratogenic in animal studies; no human data available. Fetal risk cannot be excluded in first trimester; second and third trimester use may improve fetal oxygenation without known teratogenic effects. |
| Fetal Monitoring |
■ FDA Black Box Warning
None. However, it is contraindicated in neonates with congenital heart defects dependent on right-to-left shunting.
| Serious Effects |
["Neonates with congenital heart defects dependent on right-to-left shunt (e.g., tetralogy of Fallot, tricuspid atresia)","Known hypersensitivity to nitric oxide or any component of the delivery system"]
| Precautions | ["May cause methemoglobinemia, especially with high doses or prolonged use; monitor methemoglobin levels","Rebound pulmonary hypertension upon abrupt discontinuation; weaning required","May increase bleeding risk due to inhibition of platelet aggregation; use caution in patients with bleeding disorders or on anticoagulants","Monitor for hypotension and heart rate changes"] |
Loading safety data…
| Continuous maternal methemoglobin levels, arterial blood gases, and inspiratory NO2 levels. Fetal heart rate monitoring and fetal oxygenation indices (if applicable). |
| Fertility Effects | No adverse effects on fertility reported in animal studies; no human data available. |