Inhaled corticosteroid alternatives for young children after Flovent withdrawal | Image Credit: © Pixel-Shot - © Pixel-Shot - stock.adobe.com.

Inhaled corticosteroids (ICS) are a mainstay in reducing airway inflammation and are considered the most effective treatment in children with persistent asthma.¹ Few ICS options are approved for use in infants and young children (defined as 4 years and under). A previously commonly prescribed ICS option in this age range included fluticasone propionate, sold under the brand name Flovent. Flovent was discontinued in January 2024 due to the manufacturer electing to produce only an authorized generic version of the medication.

The discontinuation of Flovent has made securing age-appropriate and financially feasible ICS options for infants and young children more challenging. Fluticasone propionate had been the prescription of choice for many pediatricians and other providers because of its efficacy and safety profile in patients younger than 4 years, ease of administration, and cost-effectiveness. Fluticasone propionate has minimal systemic bioavailability after oral inhalation as it is a substrate of CYP3A4 in the liver,² which considerably reduces the systemic adverse effect profile of fluticasone propionate, making it an excellent choice for ICS prescription.

Although generic fluticasone propionate is available, insurance coverage of this generic version is inconsistent, and out-of-pocket costs to consumers can exceed $200 for a 30-day supply if their insurance does not cover a prescription for the generic version.³ Generic medications, which are typically considered more cost-effective for consumers, are sometimes more expensive than brand-name products. US drug pricing is exceedingly complex, but in some cases, insurance companies may prefer a brand-name product over an equivalent generic due to favorable contractual prices, which may provide higher reimbursements for a brand name compared with a generic.

The impact of the market withdrawal of Flovent has been significant. Early non–peer-reviewed reports have shown a 17.5% increase in asthma-related hospitalizations in the 3 months following the discontinuation of Flovent; in the 3 to 6 months following the discontinuation, that number rose to 24.1%.⁴ These data included adults and children and are a startling example of the potential impact denying access to these medications has on asthma outcomes.

There are challenges in selecting an ICS for infants and children younger than 4 years. There are also limitations on feasible routes of administration, as young children require either a hydrofluoroalkane (HFA) inhaler or a nebulized solution for effective administration. Dry-powder inhalers (DPIs) are frequently touted as an alternative to HFA inhalers; however, DPIs are incredibly difficult for young children to use effectively as they require coordinated breathing techniques to effectively inhale the powder—something a young toddler is unlikely to achieve. Additionally, there is a lack of published literature in this age group, making it difficult to know the safety profiles of inhaler options.

Below, we discuss the different routes of administration for ICS and cover the currently available options for ICS in infants and young children.

Routes of administration

As discussed above, different options are available for inhalation devices/routes of administration of ICS. Some of the most well-known options include HFA inhalers, DPIs, and nebulized solutions. An HFA inhaler is a metered-dose inhaler, which holds the medication in a pressurized canister; upon activation of the canister, a propellant forces the medication out and into the lungs. All HFA inhalers require a spacer (a valved holding chamber) to appropriately use the medication. Spacers attach to the end of the HFA inhaler and act as a one-way valve, holding the medication within the spacer until the user inhales it; while the medication is within the spacer, it breaks into smaller droplets, allowing for more effective inhalation. An HFA inhaler is ineffective without a spacer, as the medication will not reliably reach the lungs without one. An HFA inhaler with a spacer can be used in virtually any age range and with patients of varying neurologic capabilities or with neuromuscular disorders. Spacers are equipped with masks for younger children/infants or with mouthpieces for older children/teenagers.

A DPI is a breath-actuated inhaler, which requires a strong, coordinated breath to release medication. There is no activation of the canister by pressing on the unit, and there is no propellant to force medication into the lungs. DPIs are not used with a spacer. Although DPIs represent reasonable options for older, neurotypical patients, a DPI is not an effective option in younger children who cannot coordinate a strong breath to release medication.

A nebulized solution is a liquid medication suspended in a saline solution that can be converted into a mist for inhalation by a nebulizer machine. Nebulized solutions require the patient to have access to the nebulizer equipment for use, including the machine itself, tubing, and a mask for medication delivery. Access to medical equipment/home delivery of equipment can represent an additional barrier to use. Although a nebulized solution can be used in virtually any age range and with patients of varying neurologic status, it may not be as effective as an HFA inhaler with a spacer at medication delivery. This is due to a large portion of the nebulized solution being lost to the surrounding environment or the dead space within the mouth/nose and not reaching the lungs directly,⁵ as opposed to an HFA inhaler with a spacer where there is less chance of the medication being lost to the surrounding environment.

Because of this, an HFA inhaler with a spacer or a nebulized solution is the most appropriate choice for ICS for infants and young children. Although DPIs are excellent options for older, neurotypical patients who can produce a deep, coordinated inhalation, they are not reasonable options for an infant or young toddler to use reliably.

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ICS options for infants/young children

The following is a collection of ICS options for infants/young children younger than 4 years (Table):

• Pulmicort (budesonide) is available in a nebulized solution known as Respules. This is FDA approved for children aged 12 months to 8 years. There are some limited data available indicating that this may be effective in infants younger than 12 months.⁶ Pulmicort is also available as a DPI known as the Flexhaler, which is FDA approved for children aged 6 years and older.
• Mometasone (Asmanex) is available as an HFA inhaler with a spacer for children 5 years and older. It is also available as a DPI known as the Twisthaler for children 4 years and older, which is approved for a younger age range than its HFA counterpart even though it is likely more difficult to administer in younger children.
• Beclomethasone (Qvar) is only available as a DPI known as the Redihaler for children aged 4 years and older. There is no HFA or nebulized version available. Like any DPI, the Redihaler is not used with a spacer and is not an ideal route of administration for young children.
• Fluticasone propionate is available in its generic form. The generic options available include an HFA inhaler with a spacer and a DPI option (formally known as Flovent Diskus). Both the HFA and DPI options are FDA approved for children aged 4 years and older, although there is evidence for use of the HFA inhaler with a spacer in infants and children aged 6 months and older.⁷
• Ciclesonide (Alvesco) is available as an HFA inhaler with a spacer and is FDA approved for children aged 12 years and older. However, there is limited evidence for use in children as young as 2 years for the management of recurrent wheezing.⁸

Conclusions

Unfortunately, there are limited ICS options for infants/children younger than 4 years. The only FDA-approved ICS option for infants and children younger than 4 years is Pulmicort Respules (nebulized solution); there are some limited data for efficacy in infants younger than 12 months.⁶ Generic fluticasone propionate is not FDA approved for infants, but there are some limited data for safe use in infants 6 months and older.⁷ Although ciclesonide HFA is FDA approved for only children aged 12 years and older, there are some limited data that suggest safe and effective use in children as young as 2 years.⁸

The ICS options available for children of at least 4 years of age include Pulmicort Respules (budesonide) and generic fluticasone propionate HFA. Mometasone HFA is FDA approved for children aged 5 years and older; however, there is limited evidence showing that it may be effective in younger children. As noted above, ciclesonide HFA does not carry FDA approval for this age range but has been used off-label, given its efficacy based on the available published literature. Despite being FDA approved in children as young as 4 years, DPIs are not suitable for this age range as most are unable to generate the necessary inspiratory flow for dose activation.

Selecting ICS options for infants and young children poses significant challenges. The recent market withdrawal of Flovent has made the available ICS options even more limited, and the effects on asthma-related hospitalizations have been pronounced. Feasible options for asthma management in this vulnerable age range remain challenging, both in terms of FDA-approved medications and insurance formulary availability that are not cost-prohibitive to the patient/family.

References:

1. Axelsson I, Naumburg E, Prietsch SO, Zhang L. Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth. Cochrane Database Sys Rev. 2019;6(6):CD010126. doi:10.1002/14651858.cd010126.pub2

2. Remien K, Patel P, Bowman A. Fluticasone. In: StatPearls. StatPearls Publishing; 2024. Accessed January 3, 2025. https://www.ncbi.nlm.nih.gov/books/NBK542161/

3. ACA federal upper limits. Medicaid.gov. Updated December 26, 2024. Accessed January 3, 2025. https://data.medicaid.gov/dataset/ce4cf49b-a21b-5a53-bbc3-509414940847

4. Alban C, Deckert J, Carrico N, Edwards G. Asthma visits more common after Flovent no longer manufactured. Epic Research. October 17, 2024. Accessed January 3, 2025. https://www.epicresearch.org/articles/asthma-visits-more-common-after-flovent-no-longer-manufactured

5. Smith C, Goldman RD. Nebulizers versus pressurized metered-dose inhalers in preschool children with wheezing. Can Fam Physician. 2012;58(5):528-530.

6. Baker JW, Mellon M, Wald J, Welch M, Cruz-Rivera M, Walton-Bowen K. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics. 1999;103(2):414-421. doi:10.1542/peds.103.2.414

7. Teper AM, Colom AJ, Kofman CD, Maffey AF, Vidaurreta SM, Bergadá I. Effects of inhaled fluticasone propionate in children less than 2 years old with recurrent wheezing. Pediatr Pulmonol. 2004;37(2):111-115. doi:10.1002/ppul.10400

8. Brand PL, García-García M, Morison A, Vermeulen JH, Weber HC. Ciclesonide in wheezy preschool children with a positive asthma predictive index or atopy. Respir Med. 2011;105(11):1588-1595. doi:10.1016/j.rmed.2011.07.017