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Selective Pulmonary Vasodilator Pregnancy: Fertility: no fertility studies have been performed. Pregnancy: 'The effect of the administration of Neophyr in pregnant women is unknown. Animal studies are insufficient. The potential risk for humans is unknown. Neophyr should not be used during pregnancy unless clearly necessary, such as in situations of life support.' Breast-feeding: 'It is not known whether Neophyr passes into human breast milk. The excretion of Neophyr in milk has not been studied in animals. Exposure to nitric oxide in humans during lactation should be avoided.'

Nitric Oxide (Inhaled — iNO)

Brand names: INOmax, Noxivent

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator delivered into the ventilator circuit, used in critical care for pulmonary hypertension and severe hypoxaemic respiratory failure, including persistent pulmonary hypertension of the newborn.

Adult dose

Dose: Adults - perioperative pulmonary hypertension in conjunction with heart surgery (to selectively decrease pulmonary arterial pressure and improve right ventricular function and oxygenation): starting dose 20 ppm of inhaled gas; may be increased up to 40 ppm if the lower dose has not provided sufficient clinical effect; give the lowest effective dose and wean down to 5 ppm provided pulmonary artery pressure and systemic arterial oxygenation remain adequate at this lower dose
Route: Inhalation - diluted in the ventilator circuit with an oxygen/air mix by a CE-marked nitric oxide delivery device (mechanical ventilation); direct endotracheal administration without dilution is contra-indicated
Frequency: Constant inhaled concentration for the duration of treatment; titrate after a minimum of 10 minutes if response is insufficient; common treatment times are 24-48 hours (up to 7 days has been given perioperatively); attempt weaning at least every 12 hours once stable on a low dose
UK SPC section 4.2, Adults: 'The starting dose of inhaled nitric oxide is 20 ppm (parts per million) of inhaled gas. The dose may be increased up to 40 ppm if the lower dose has not provided sufficient clinical effect. The lowest effective dose should be administered and the dose should be weaned down to 5 ppm provided that the pulmonary artery pressure and systemic arterial oxygenation remain adequate at this lower dose.' 'The effects of inhaled nitric oxide are rapid, decrease in pulmonary artery pressure and improved oxygenation is seen within 5-20 minutes. In case of insufficient response the dose may be titrated after a minimum of 10 minutes. Consideration should be given to discontinuation of treatment if no beneficial physiological effects are apparent after a 30-minute trial of therapy.' 'Inhaled NO has been given for time periods up to 7 days in the perioperative setting, but common treatment times are 24-48 hours.' Weaning: the dose should be incrementally reduced to 1 ppm for 30 minutes with close observation of systemic and central pressure, and then turned off; weaning should be attempted at least every 12 hours when the patient is stable on a low dose; too rapid weaning risks a rebound increase in pulmonary artery pressure with circulatory instability. Product: Neophyr 450 ppm mol/mol medicinal gas (nitric oxide 450 ppm in nitrogen). Use only after conservative support has been optimised, under close monitoring of haemodynamics and oxygenation, on the prescription of an anaesthetist or intensive care physician in a cardio-thoracic unit trained in the delivery system. Monitoring: continuous NO2 monitoring (keep NO2 as low as possible, below 0.5 ppm; if NO2 exceeds 1 ppm reduce the dose and/or FiO2); methaemoglobin measured within one hour of starting and, in adults undergoing heart surgery, the dose decreased if methaemoglobin rises to a level that compromises oxygen delivery. The SPC prints no maximum dose other than the titration limit of 40 ppm. Scope: this card covers only the licensed adult indication in this SPC. Acute respiratory distress syndrome (ARDS) is not a licensed indication in this SPC and no ARDS dose is given. The same SPC also licenses treatment of hypoxic respiratory failure with pulmonary hypertension in newborn infants of 34 weeks gestation or more, and perioperative pulmonary hypertension in children aged 0-17 years; those paediatric and neonatal regimens are not transcribed here - use specialist neonatal or paediatric guidance and a children's formulary.

Dose adjustments

Renal

SPC section 4.2: 'No relevant information for dosage adjustment recommendation on special populations, such as renal/hepatic impairment or geriatric, has been found. Therefore caution is recommended in these populations.'

Hepatic

SPC section 4.2: 'No relevant information for dosage adjustment recommendation on special populations, such as renal/hepatic impairment or geriatric, has been found. Therefore caution is recommended in these populations.'

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via MHRA Products — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Newborns with known dependency on a right-to-left blood shunt, or newborns with significant left-to-right shunt (section 4.3)
  • Patients with congenital or acquired deficiency of methaemoglobin reductase (MetHb reductase) or glucose-6-phosphate dehydrogenase (G6PD) (section 4.3)
  • Hypersensitivity to the active substance or to any of the excipients (section 4.3)
  • Direct endotracheal administration without dilution is contra-indicated because of the risk of local mucous membrane lesion (section 4.2)

Side effects

  • Rebound reaction on abrupt discontinuation - decrease in oxygenation, increase in central pressure and subsequent decrease in systemic blood pressure; the most commonly reported adverse reaction (section 4.8). Rapid rebound reactions such as intensified pulmonary vasoconstriction after sudden withdrawal have precipitated cardiovascular collapse
  • Listed in the section 4.8 table: thrombocytopenia, hypokalaemia, hypotension, atelectasis, hyperbilirubinaemia, increased methaemoglobin. Post-marketing surveillance: headache (symptom experienced by personnel after accidental environmental exposure); increased pulmonary artery pressure, hypotension and hypoxaemia (associated with acute withdrawal and with dose errors from the delivery system)
  • Inhaled nitric oxide therapy may cause an increase in methaemoglobin (section 4.8)
  • Frequency bands are not assigned here because the section 4.8 table layout is not clearly readable in the source text

Interactions

  • No interaction studies have been performed; a clinically significant interaction with other medicinal products used in hypoxic respiratory failure cannot be excluded (section 4.5)
  • Oxygen: nitric oxide oxidises rapidly in oxygen to nitrogen dioxide (NO2), which is toxic to the bronchiolar epithelium and alveolo-capillary membrane; NO2 must be below 0.5 ppm at nitric oxide doses under 20 ppm, and the dose must be reduced immediately if NO2 exceeds 1 ppm (section 4.5)
  • NO donors (e.g. sodium nitroprusside, nitroglycerine): additive effect with the risk of methaemoglobinaemia (section 4.5)
  • Methaemoglobin inducers (e.g. alkyl nitrates, sulphonamides, prilocaine in any formulation): higher risk of methaemoglobinaemia - use with caution (section 4.5)
  • Other vasodilators acting by the cGMP or cAMP systems (e.g. sildenafil): additive effects on central circulation, pulmonary artery pressure and right ventricular performance; combine with caution (section 4.5)

Monitoring

  • Nitrogen dioxide (NO2): continuous monitoring is required; keep as low as possible, below 0.5 ppm; if above 1 ppm reduce the dose and/or FiO2 after excluding a malfunction; alarms set at NO +/- 2 ppm of the prescribed dose, NO2 maximum 1 ppm, FiO2 +/- 0.05 (sections 4.2 and 4.5)
  • Methaemoglobin: measure within 1 hour of starting; in adults undergoing heart surgery, decrease the dose and consider reducing agents such as methylene blue if methaemoglobin rises to a level that compromises oxygen delivery (section 4.2)
  • Haemodynamics and oxygenation under close monitoring; before starting, consider pulmonary artery catheterisation or echocardiographic assessment of central haemodynamics, with careful monitoring of cardiac output, left atrial pressure or pulmonary capillary wedge pressure, because increased pulmonary blood flow in patients with left ventricular dysfunction can lead to cardiac insufficiency and pulmonary oedema (section 4.4)
  • Bleeding time: monitoring recommended during administration for more than 24 hours in patients with numerical or functional platelet abnormalities (section 4.4; text truncated at source)
  • Do not stop abruptly - risk of rebound pulmonary hypertension; guarantee continuity of supply during transport, with a reserve cylinder and back-up administration system (sections 4.2 and 4.4)

Clinical monograph

How it works

Delivered to ventilated lung units, it diffuses into pulmonary vascular smooth muscle and raises cyclic GMP to cause local vasodilatation, improving ventilation–perfusion matching while being rapidly inactivated by haemoglobin so systemic effects are minimal.

Prescribing in practice

  • It must never be stopped abruptly because rebound pulmonary hypertension and hypoxaemia can occur; wean gradually.
  • It can cause methaemoglobinaemia and generates toxic nitrogen dioxide, so inspired nitrogen dioxide and methaemoglobin must be monitored.
  • Delivery requires a dedicated, calibrated delivery and monitoring system integrated with the ventilator.

Monitoring

Monitor oxygenation, methaemoglobin levels, and inspired nitrogen dioxide concentration, and observe closely during weaning for rebound deterioration.

Counselling the patient

  • This therapy is delivered through the breathing machine and continuously monitored in intensive care.
  • The treatment is reduced gradually rather than stopped suddenly.

Evidence & guidelines

Use is supported by critical care and neonatal practice and product information; consult current prescribing references and the SPC.

Reference: Cochrane Review: iNO for ARDS (Adhikari et al. 2014); INNOVO Trial (Lancet 2002 — PPHN); MHRA SPC INOmax; ESC/ERS Pulmonary Hypertension Guidelines 2022; Surviving Sepsis Campaign 2021; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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