Humana Commercial Clinical Policy

Humana Inhaled Nitric Oxide Form

Effective Date

11/02/2023

Last Reviewed

NA

Original Document

  Reference



Description

Inhaled nitric oxide (iNO) is a pulmonary vasodilator, used for the treatment of hypoxic respiratory failure associated with persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs after birth when there is increased pulmonary vascular resistance that causes right-to-left shunting of blood leading to severe hypoxemia. PPHN is often associated with pulmonary parenchymal abnormalities such as alveolar capillary dysplasia, lung hypoplasia, meconium aspiration, pneumonia and sepsis. In some neonates, there is no evidence of parenchymal disease, and the cause is unknown.

When nitric oxide is inhaled, pulmonary vasodilation occurs and an increase in the partial pressure of arterial oxygen results. Dilation of pulmonary vessels in well- ventilated lung areas redistributes blood flow away from lung areas where ventilation to perfusion ratios are poor. Examples of commercially available brands of nitric oxide include, but may not be limited to, GENOSYL, INOmax and Noxivent.

iNO is most often utilized in conjunction with ventilatory support in term or near-term (34 or more weeks gestation) neonates (28 days of age or younger) to improve oxygenation and decrease the need for extracorporeal membrane oxygenation (ECMO). iNO may also be administered to infants and children for postoperative management of pulmonary hypertension. Another established use for iNO is with acute vasoreactivity testing for pulmonary arterial hypertension. It is performed during right heart catheterization procedures to determine how much the pulmonary blood vessels can relax over a period of time and help identify individuals who might respond favorably to calcium channel blockers.

Other proposed uses for iNO include, but may not be limited to, acute respiratory distress syndrome in adults, bronchopulmonary dysplasia or for treatment of pain related to sickle cell disease. (Refer to Coverage Limitations section)

Coverage Determination

Commercial Plan members: requests for iNO therapy greater than 14 days require review by a medical director.

Humana members may be eligible under the Plan for the use of iNO in conjunction with ventilatory support when the following criteria are met:

  • Neonate at or greater than 34 weeks gestation; AND
  • Failure of, contraindication or intolerance to conventional therapy (eg, high concentrations of oxygen, high frequency ventilation, hyperventilation, induction of alkalosis, neuromuscular blockade and sedation); AND
  • Hypoxic respiratory failure associated with clinical or echocardiographic evidence of PPHN; AND
  • Maximum duration of treatment is 14 days or until oxygen desaturation has been resolved, whichever occurs first

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Humana members may be eligible under the Plan for the use of iNO for postoperative management of pulmonary hypertension in infants and children with congenital heart disease.

Humana members may be eligible under the Plan for the use of iNO for acute vasoreactivity testing in pulmonary arterial hypertension.

Coverage Limitations

Humana members may NOT be eligible under the Plan for the use of iNO for any indications other than those listed above including, but not limited to:

  • Acute respiratory distress syndrome in an adult; OR
  • Acute vasoreactivity testing in an individual with pulmonary veno-occlusive disease (PVOD); OR
  • Bronchopulmonary dysplasia; OR
  • Chronic obstructive pulmonary disease (COPD); OR
  • Hepatopulmonary syndrome; OR
  • Neonatal respiratory distress syndrome without PPHN; OR
  • Neonate less than 34 weeks gestation; OR
  • Neonate with unrepaired congenital diaphragmatic hernia (CDH); OR
  • Prevention of primary graft dysfunction following lung transplantation; OR
  • Treatment of pain crisis in sickle cell disease

This is considered experimental/investigational as it is not identified as widely used and generally accepted for any other proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

Inhaled Nitric Oxide Effective Date: 11/02/2023
Revision Date: 11/02/2023
Review Date: 11/02/2023
Policy Number: HUM-0511-012

Page: 4 of 9

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Additional information about pulmonary hypertension may be found from the following websites:

Background
  • American Heart Association
  • American Lung Association
  • National Heart, Lung and Blood Institute
  • National Library of Medicine
Medical Alternatives

Physician consultation is advised to make an informed decision based on an individual’s health needs.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Codes are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement.

Inhaled Nitric Oxide Effective Date: 11/02/2023
Revision Date: 11/02/2023
Review Date: 11/02/2023
Policy Number: HUM-0511-012

Page: 5 of 9

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

No code(s) identified

References

  1. Agency for Healthcare Research and Quality (AHRQ). Evidence Report/Technology Assessment (ARCHIVED). Inhaled nitric oxide in preterm infants. https://www.ahrq.gov. Published October 2010. Updated October 2014. Accessed September 29, 2023.
  2. American Academy of Pediatrics (AAP). Clinical Report. Use of inhaled nitric oxide in preterm infants. https://www.aap.org.
  1. American Academy of Pediatrics (AAP). Off-label use of inhaled nitric oxide after release of NIH consensus statement. https://www.aap.org. Published April 2015. Accessed October 6, 2023.
  2. American Academy of Pediatrics (AAP). Policy Statement. Use of inhaled nitric oxide. https://www.aap.org. Published August 2000. Updated December 2009. Accessed September 29, 2023.
  3. American Association for Respiratory Care (AARC). AARC Clinical Practice Guideline. Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure. https://www.aarc.org. Published December 2010. Accessed October 6, 2023.
  4. American College of Chest Physicians. Therapy for pulmonary arterial hypertension in adults. Update of the CHEST guideline and expert panel report. https://www.chestnet.org. Published March 2019. Accessed October 6, 2023.
  5. American Heart Association (AHA). ACCF/AHA 2009 Expert consensus document on pulmonary hypertension. https://www.heart.org. Published April 28, 2009. Accessed October 6, 2023.
  6. American Heart Association (AHA). Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. https://www.heart.org. Published November 24, 2015. Accessed October 6, 2023.
  7. ClinicalKey. Drug Monograph. Nitric oxide. https://www.clinicalkey.com. Updated January 16, 2020. Accessed October 5, 2023.
  8. ClinicalKey. Nativi-Nicolau J, Ryan JJ, Fang JC. Hemodynamics in heart failure. In: Felker GM, Mann DL. Heart Failure: A Companion to Braunwald’s Heart Disease. 4th ed. Elsevier; 2020:467-486.e2. https://www.clinicalkey.com. Accessed October 6, 2023.
  9. Cochrane Library. Cochrane Database of Systematic Reviews. Inhaled nitric oxide for treating pain crises in people with sickle cell disease (review). https://www.cochrane.org. Published July 8, 2022. Accessed October 6, 2023.
  10. ECRI Institute. Clinical Evidence Assessment. Inhaled nitric oxide for vasoreactivity and pulmonary hypertension treatment. https://www.ecri.org. Published March 8, 2005. Updated February 22, 2023. Accessed September 28, 2023.
  11. ECRI Institute. Hotline Response (ARCHIVED). Inhaled prostacyclins as alternatives to nitric oxide for treating pulmonary hypertension in neonates and children. https://www.ecri.org. Published April 15, 2015. Accessed September 28, 2023.
  12. ECRI Institute. Hotline Response (ARCHIVED). Nitric oxide for treating pulmonary hypertension in pediatric cardiac patients. https://www.ecri.org. Published April 4, 2012. Updated July 9, 2013. Accessed September 28, 2023.
  13. ECRI Institute. Product Brief (ARCHIVED). INOmax inhaled nitric oxide (Mallinckrodt/INO Therapeutics LLC) for treating pulmonary hypertension in neonates. https://www.ecri.org. Published February 27, 2017. Accessed September 28, 2023.
  14. Hayes, Inc. Clinical Research Response (ARCHIVED). Inhaled nitric oxide versus inhaled Veletri (Epoprostenol) for the management of acute pulmonary arterial hypertension. https://evidence.hayesinc.com. Published May 22, 2018. Accessed October 21, 2021.
Inhaled Nitric Oxide Effective Date: 11/02/2023
Revision Date: 11/02/2023
Review Date: 11/02/2023
Policy Number: HUM-0511-012

Page: 6 of 9

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

  1. Hayes, Inc. Health Technology Assessment. Inhaled nitric oxide for the treatment of respiratory failure in preterm newborns. https://evidence.hayesinc.com. Published November 6, 2018. Updated January 24, 2023. Accessed September 28, 2023.
  2. Hayes, Inc. Health Technology Brief (ARCHIVED). Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in adults. https://evidence.hayesinc.com. Published March 31, 2014. Updated March 2, 2016. Accessed September 28, 2023.
  3. Hayes, Inc. Medical Technology Directory (ARCHIVED). Inhaled nitric oxide for the treatment of persistent pulmonary hypertension in term and near-term newborns. https://evidence.hayesinc.com. Published January 15, 2009. Updated January 22, 2013. Accessed September 28, 2023.
  4. Merative Micromedex. Nitric oxide. https://www.micromedexsolutions.com. Updated September 25, 2023. Accessed October 4, 2023.
  5. UpToDate, Inc. Acute respiratory distress syndrome: fluid management, pharmacotherapy and supportive care in adults. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  6. UpToDate, Inc. Bronchopulmonary dysplasia: prevention. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  7. UpToDate, Inc. Congenital diaphragmatic hernia in the neonate. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  8. UpToDate, Inc. Hepatopulmonary syndrome in adults: natural history, treatment, and outcomes. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
Inhaled Nitric Oxide Effective Date: 11/02/2023
Revision Date: 11/02/2023
Review Date: 11/02/2023
Policy Number: HUM-0511-012

Page: 8 of 9

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

  1. UpToDate, Inc. Inhaled nitric oxide in adults: biology and indications for use. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  2. UpToDate, Inc. Meconium aspiration syndrome: management and outcome. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  3. UpToDate, Inc. Persistent pulmonary hypertension of the newborn (PPHN): management and outcome. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  4. UpToDate, Inc. Primary lung graft dysfunction. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  5. UpToDate, Inc. Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): treatment and prognosis. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  6. UpToDate, Inc. Pulmonary hypertension in children: classification, evaluation, and diagnosis. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  7. UpToDate, Inc. Pulmonary hypertension in children: management and prognosis. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  8. UpToDate, Inc. Respiratory distress syndrome (RDS) in preterm infants: management. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
  9. UpToDate, Inc. Treatment and prognosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis in adults. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.
Inhaled Nitric Oxide Effective Date: 11/02/2023
Revision Date: 11/02/2023
Review Date: 11/02/2023
Policy Number: HUM-0511-012

Page: 9 of 9

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

  • Treatment of pulmonary arterial hypertension (group 1) in adults: pulmonary hypertension-specific therapy. https://www.uptodate.com. Updated September 2023. Accessed October 2, 2023.