Are there data to support the use of oral albuterol for acute respiratory symptoms when inhalation treatment is unavailable or inappropriate?

Introduction

The rapid spread of a coronavirus disease 2019 (COVID-19) has led to shortages of personal protective equipment (PPE) and critical medications.1 Albuterol metered-dose inhaler (MDI) is one of the many drugs used to manage the symptoms of COVID-19 that is currently on shortage due to increased demand and supplier allocation.2 In the first two weeks of March 2020, hospitals in the United States ordered more than twice as many albuterol MDIs compared to January and February.3 A disruption to the supply of this medication not only impacts patients with COVID-19 but also has the potential to impact patients with chronic respiratory conditions such as asthma.4

Bronchodilator use in COVID-19 disease

Respiratory symptoms including difficulty breathing and cough are commonly seen in patients with COVID-19 infection, and most patients have required inhaled bronchodilator medications (mostly albuterol) for acute symptom relief.4 The clinical effects of bronchodilator medications delivered by nebulization vs MDI are similar.5 However, since nebulization may generate respiratory droplets that can linger in the air for 1 to 2 hours after treatment, this route of administration is not recommended for hospitalized patients with suspected or confirmed COVID-19 infection due to the increased risk for viral transmission.6 Therefore, MDIs are the preferred devices for the delivery of quick-acting bronchodilator therapies in this population.5,6 According to the American College of Allergy, Asthma and Immunology, nebulized therapy can potentially be used by patients with COVID-19 disease in the home setting, as long as treatments are administered in places where the air is not recirculated into the home (ie, a porch, patio, or in a garage) or areas with easy to clean surfaces or surfaces that do not need cleaning.6 Nonetheless, in the inpatient setting, administration of drugs via nebulizer would require additional use of already critically low supplies of PPE.

A less explored alternative to albuterol MDIs that also bypasses concerns of aerosol generation seen with nebulizer treatment is orally administered albuterol.  The remainder of this review will summarize data on the use of oral albuterol for acute respiratory symptoms common to COVID-19 infection.

Oral albuterol for acute respiratory symptoms

No studies have evaluated the use of oral albuterol for patients with COVID-19 associated respiratory symptoms. To evaluate the feasibility of using oral albuterol in this setting, a literature search was performed to identify publications summarizing efficacy outcomes related to the use of oral albuterol for the acute relief of respiratory symptoms seen in COVID-19 disease, including cough and shortness of breath.4 Data for the use of oral albuterol for respiratory symptoms not seen in COVID-19 infection (wheezing, etc) are not summarized.

In 2015, Dr. O’Reilly and colleagues published a paper summarizing results of a literature search focused on the use of oral albuterol for improvement in clinical outcomes and surrogate markers of lung function in children with asthma in resource-poor settings.7 Six unique studies were identified, all of which had methodological differences concerning study design and populations included. Overall, a faster onset of action was seen with inhaled formulations, while oral formulations resulted in a more sustained response. Both formulations demonstrated improvements in lung function compared with no treatment. Additional publications describing the use of oral albuterol in infants with bronchiolitis have not demonstrated significant improvements in symptoms vs placebo.7-10 For the treatment of non-asthmatic acute cough, one trial each in adults and children did not find oral albuterol effective for reducing the frequency, duration, or severity of the cough.11,12

Discussion

The COVID-19 disease pandemic has led to shortages of critical drugs and supplies needed to adequately treat patients with this potentially life-threatening and highly contagious infection.1 Albuterol (internationally referred to as salbutamol) is a beta2 agonist available as an MDI, solution for nebulization, and oral tablet and syrup.14 It is widely recognized that inhaled formulations of albuterol are preferred to oral dosage forms due to their quicker onset of action (<5 vs <30 minutes) and lower risk for systemic adverse events. Generally, the choice between nebulization or MDI delivery of short-acting bronchodilators is driven by patient preference, convenience, and ease of administration.5 However, MDI administration is preferred for patients with COVID-19 disease, especially in the inpatient setting, due to a lower risk for viral transmission and a lesser need for additional PPE.5,6

There are no studies evaluating the use of oral albuterol for patients with respiratory symptoms due to COVID-19 infection. Clinical trials comparing oral and inhaled albuterol are generally conducted in resource-poor settings where oral formulations of albuterol are implemented as a potentially effective and low-cost treatment for children with asthma.7 However, since not all symptoms of asthma overlap with those of COVID-19 disease, the application of these data to patients with COVID-19 is unclear.4

The use of oral albuterol in infants with bronchiolitis did not result in symptomatic or clinical improvements vs placebo.8-11 Similar to COVID-19 disease, symptoms of bronchiolitis include coughing and difficulty breathing.15 However, bronchiolitis generally does not cause fever or only a slight fever and wheezing may be present. Most cases of bronchiolitis are caused by respiratory syncytial virus, but the illness can also be caused by viruses that cause the common cold or flu. No reports of COVID-19 associated bronchiolitis have been reported at this time. Therefore, the application of this data to patients with COVID-19 is also unclear.

Two trials found oral albuterol ineffective for reducing the frequency, duration, or severity of non-specific cough.12,13 Based on this information, oral albuterol may not be helpful for cough due to COVID-19.

Best practices for mitigation of MDI shortages

In response to the ongoing shortage of albuterol MDIs and potential risks of using nebulized albuterol in patients COVID-19 infection, the Institute for Safe Medication Practices (ISMP) has recently proposed several measures for conserving available MDI supply, including:16,17

  • implementation of “common canister” protocols where a disinfection procedure is established in order to be able to administer doses from the same MDI to multiple patients using a patient-specific spacer
  • use of a patients’ home MDIs throughout hospitalization
  • sending patients home with the MDI that was used throughout hospitalization to prevent unnecessary waste

The approval of the first generic albuterol inhaler on April 8, 2020, is also expected to help mitigate the increased demand for this product.6

Conclusion

The feasibility of using oral albuterol for COVID-19 associated respiratory symptoms has yet to be determined. Clinicians looking to mitigate the shortage of albuterol MDIs may refer to recent  ISMP publications for recommended strategies to conserve the current supply of these products. The recent approval of a generic albuterol inhaler will also help to boost supply.

References

  1. Coronavirus (COVID-19) supply chain update. Food and Drug Administration (FDA). February 27, 2020. Accessed April 10, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-supply-chain-update
  2. Drug shortages list. American Society of Health-System Pharmacists (ASHP). Accessed April 10, 2020. https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=647
  3. Dodge B. Hospitals and pharmacies risk running our of inhalers as the coronavirus strains supplies. Business Insider website. March 24, 2020. Accessed April 10, 2020. https://www.businessinsider.com/hospitals-may-run-out-of-inhalers-as-coronavirus-strains-supply-2020-3
  4. Important COVID-19 information for those with asthma and/or allergies. American College of Allergy Asthma and Immunology (ACAAI). Updated April 9, 2020. Accessed April 10, 2020. https://acaai.org/news/important-covid-19-information-those-asthma-andor-allergies
  5. A message to asthma sufferers about a shortage of albuterol metered-dose inhalers. American College of Allergy Asthma and Immunology (ACAAI). Updated April 9, 2020. Accessed April 10, 2020. https://acaai.org/news/message-asthma-sufferers-about-shortage-albuterol-metered-dose-inhalers
  6. O’Reilly DA, Awale A, Cartledge PT. Question 2: Blast from the past: is oral salbutamol useful in resource-poor settings? Arch Dis Child. 2015;100(8):806-809. doi: 10.1136/archdischild-2015-309141.
  7. Gupta P, Aggarwal A, Gupta P, Sharma KK. Oral salbutamol for symptomatic relief in mild bronchiolitis a double blind randomized placebo controlled trial. Indian Pediatr 2008;45(7):547–53.
  8. Patel H, Gouin S, Platt RW. Randomized, double-blind, placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis. J Pediatr. 2003;142(5):509-514.
  9. Cengizlier R, Saraçlar Y, Adalioğlu G, et al. Effect of oral and inhaled salbutamol in infants with bronchiolitis. Acta Paediatr Jpn. 1997;39(1):61-63. doi: 10.1111/j.1442-200x.1997.tb03557.x.
  10. Gadomski AM, Aref GH, el Din OB, et al. Oral versus nebulized albuterol in the management of bronchiolitis in Egypt. J Pediatr. 1994;124(1):131-138.
  11. Bernard DW, Goepp JG, Duggan AK, Serwint JR, Rowe PC. Is oral albuterol effective for acute cough in non-asthmatic children? Acta Paediatr. 1999;88(4):465-467.
  12. Littenberg B, Wheeler M, Smith DS. A randomized controlled trial of oral albuterol in acute cough. J Fam Pract. 1996;42(1):49-53.
  13. Lexicomp. Wolters Kluwer; 2020. Accessed April 9, 2020. https://online.lexi.com/lco/action/home
  14. Silver AH, Nazif JM. Bronchiolitis. Pediatr Rev. 2019;40(11):568-576.
  15. Revisiting the need for MDI common canister protocols during the COVID-19 pandemic. Institute for Safe Medication Practices (ISMP). March 26, 2020. Accessed April 10, 2020. https://ismp.org/resources/revisiting-need-mdi-common-canister-protocols-during-covid-19-pandemic
  16. Shared MDIs: can cross-contamination be avoided. Institute for Safe Medication Practices (ISMP). April 9, 2020. Accessed April 10, 2020. https://www.ismp.org/resources/shared-mdis-can-cross-contamination-be-avoided

Prepared by:
Katherine Sarna, PharmD, BCPS
Clinical Assistant Professor Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

May 2020

The information presented is current as April 9, 2020. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.

Return to top