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by Matt Lester, RPh, MBA, PCCA Clinical Compounding Pharmacist, and Natalie Rea, PharmD Candidate, PCCA Clinical Services Intern

Eosinophilic Esophagitis

EoE is a chronic condition of the immune system. In patients with this condition, eosinophiles — a type of white blood cell — collect in the inner lining of the esophagus, which causes chronic inflammation.2 EoE is considered a rare condition in the U.S., but prevalence has increased over the past two decades. EoE affects about 1 in 2,000 people.3 Some common symptoms include difficulty swallowing, abdominal pain, decreased appetite, nausea and vomiting. There are currently two FDA-approved treatments for EoE — a monoclonal subcutaneous (SC) injection and, now, the new oral budesonide suspension.

Corticosteroid Options

When considering oral treatments of EoE, other than budesonide, the only other recommended medication is fluticasone (another oral corticosteroid).4,5 Oral corticosteroids help patients with EoE by reducing inflammatory cells and fibrosis. However, the caveat to using fluticasone is the only commercially available product is the inhaler. The current recommendation for fluticasone is to spray the inhaler into the mouth, let it pool, and then slowly swallow to allow the fluticasone to run down and come into direct contact with the affected tissue. The recommended dosing range in the literature is 440-880 mcg twice daily.4 By compounding a fluticasone suspension for patients, adherence can possibly be improved by making the medication more palatable and convenient to administer as opposed to using an inhaler.

Now that we know the oral corticosteroids used for EoE, what other compounded options can we prepare for patients who cannot tolerate commercially available drugs?

Other Compounding Options

Many patients who have EoE are already on an antihistamine (e.g., levocetirizine or ketotifen) and/or leukotriene antagonist (e.g., montelukast).6 These medications have shown symptomatic relief in patients and could be something that can be added into a suspension to help reduce symptoms and pill burden. Antihistamines work by antagonizing the histamine receptor on mast cells to block the release of histamine and act as an eosinophil inhibitor. Leukotriene antagonists have been shown to provide symptomatic relief, which is theorized to be due to the mechanism of selectively blocking the D4 receptors of leukotrienes present in eosinophils.

Pivoting away from previously mentioned treatments, low-dose naltrexone (LDN) could be an option for EoE. Evidence shows LDN reduces inflammation and blocks pain receptors.7,8 There currently is no direct research utilizing LDN for the treatment of EoE, but LDN has been used for many inflammatory diseases such as Crohn's, MS and fibromyalgia.9,10 There have also been some positive case reports using LDN for EoE.11 EoE is primarily an inflammatory disease with a very common symptom of abdominal pain, so LDN could potentially be a promising treatment for these patients.

The goal of treating EoE is to reduce inflammation and we can do that by improving adherence of the previously mentioned APIs to the mucosal membrane of the esophagus. Keeping drugs on the mucosal surface longer can potentially enhance the effect of these medications. For oral preparations, using PCCA MucoLox™ as the base vehicle offers potential benefits not available in commercially available medications. Its one-of-a-kind polymer network provides improved moisturization, mucoadherence and superior film-forming action that won’t easily wash away. When used with APIs, its mucoadhesive properties may prolong API contact time. In addition, the oral preparation can include flavoring to make the medicine more palpable, especially for young children.12

Despite the increase in prevalence of EoE, it is still a poorly researched condition. While compounded medications represent a valuable option, they should be considered with a comprehensive treatment approach that includes dietary modifications, lifestyle adjustments and regular monitoring. The more we understand EoE, the easier it gets to spot and treat. This means earlier diagnosis, better care and a more dependable treatment regimen.

PCCA members may access our PCCA Science technical reports for MucoLox on the Members-Only Website. Members with clinical services access may search our  formulation database for oral formulas using MucoLox, as well as contact the PCCA Clinical Services team for help with compounding preparations for EoE patients.

References

  1. Takeda. (2024) EOHILIA ™ Prescribing Information. Accessed March 2024 at https://content.takeda.com/?contenttype=PI&product=EOH&language=ENG&country=USA&documentnumber=1
  2. Roussel, J.M., Pandit, S. (updated 2023). Eosinophilic Esophagitis. StatPearls Publishing, Treasure Island (FL). Accessed March 2024 at https://www.ncbi.nlm.nih.gov/books/NBK459297/
  3. NORD. (updated 2024.) Eosinophilic Esophagitis. Accessed March 2024 at https://rarediseases.org/rare-diseases/eosinophilic-esophagitis/
  4. Hirano, I., Chan, E.S., Rank, M.A., et al. (2020) AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Ann Allergy Asthma Immunol.124(5):416-423. Accessed March 2024 at doi:10.1016/j.anai.2020.03.020
  5. Nennstiel, S., Schlag, C. (2020). Treatment of eosinophlic esophagitis with swallowed topical corticosteroids. World J Gastroenterol. 26(36):5395-5407. Accessed March 2024 at doi:10.3748/wjg.v26.i36.5395
  6. Dellon, E.S., Jensen, E.T., Martin, C. et al. (2014) Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol.12(4):589-96.e1. Accessed March 2024 at doi:10.1016/j.cgh.2013.09.008
  7. Patten, D.K., Schultz, B.G., Berlau, D.J. (2018) The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders. Pharmacotherapy.38(3):382-389. Accessed March 2024 at doi:10.1002/phar.2086
  8. Toljan, K., Vrooman, B. (2018) Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization. Med Sci (Basel). 6(4):82. Accessed March 2024 at doi:10.3390/medsci6040082
  9. Schroeder, S., Atkins, D., Furuta, G.T. (2010) Recent advances in the treatment of eosinophilic esophagitis. Expert Rev Clin Immunol. 6(6):929-937. Accessed March 2024 at doi:10.1586/eci.10.65
  10. Parkitny, L., Younger, J. (2017 ). Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines.;5(2):16. Accessed March 2024 at doi:10.3390/biomedicines5020016
  11. SKCSnowmass. (2022) EOS Connections, Eosinophilic Esophagitis (EoE) Accessed March 2024 at https://www.inspire.com/groups/eos-connections/discussion/low-dose-naltrexone-for-eoe/
  12. Song. G., Banov, D., Bassani, A.S., Valdez, B.C. (2017) Evaluation of the Safety, Cell Migration, and Mucoadhesive Properties of a Mucoadhesive Polymer Blend in Human Oral Mucosa. AAPS PharmSciTech. 18(5):1617-1623. Accessed March 2024 at doi:10.1208/s12249-016-0630-z

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.



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