Abstract
This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu.
THERAPUETIC CONSIDERATIONS
Unsupported. In a small case series and prospective review including adult patients, montelukast demonstrated a symptomatic but not histologic improvement and was not effective in maintaining steroid-induced remission of eosinophilic esophagitis.1,2
Guidelines from the American College of Gastro-enterology (ACG) and consensus recommendations from the American Gastroenterological Association (AGA)/North American Society of Pediatric Gastro-enterology, Hepatology, and Nutrition (NASPGHAN) regarding diagnosis and management of eosinophilic esophagitis state that the efficacy of montelukast in patients with eosinophilic esophagitis has not been established and its use is not recommended.3,4
RATIONALE
Eosinophilic esophagitis is a chronic immune-mediated inflammatory condition characterized by clinical symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Food and environmental antigens stimulate an inflammatory response, resulting in secretion of proinflammatory and profibrotic mediators, local tissue damage, mast cell and fibroblast recruitment, and ultimately tissue fibrosis and remodeling. Diagnosis is based on clinical and pathologic findings, including the presence of symptoms related to esophageal dysfunction, eosinophil-predominant inflammation on esophageal biopsy (15 or more eosinophils per high-power field [HPF]), eosinophilia isolated to the esophagus that does not resolve with administration of a proton pump inhibitor, and exclusion of all potential secondary causes. Recommended treatments in symptomatic patients with persistent strictures include dietary elimination, topical corticosteroids, and esophageal dilation.3–5
POPULATION
Patients with eosinophilic esophagitis.
DOSING STUDIED
Unsupported use. Dosing not recommended.
DISCUSSION
Unsupported. In a small case series and prospective review including adult patients, montelukast demonstrated a symptomatic but not histologic improvement and was not effective in maintaining steroid-induced remission of eosinophilic esophagitis.1,2
Guidelines
American College of Gastroenterology and American Gastroenterological Association/North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition
ACG guidelines and AGA/NASPGHAN consensus recommendations evaluated the role of montelukast in the management of eosinophilic esophagitis. The ACG guidelines state that the use of montelukast is not recommended because efficacy has not been established. A 2011 update to the AGA/NASPGHAN consensus guidelines reports that leukotriene receptor antagonists may produce symptomatic improvement when administered at high doses; however, leukotriene receptor antagonists do not appear to have a demonstrable effect on eosinophilic esophagitis and are not recommended. The lack of clinical and histological benefits in addition to the potential for adverse effects outweigh potential benefits.2,4,6
Case Series
A case series described 8 adult patients with eosinophilic esophagitis treated with montelukast for a median of 14 months. Montelukast was initiated at a dose of 10 mg daily and titrated, if required, to a maximum of 100 mg daily. When symptomatic relief was established, montelukast was reduced to a maintenance dose of 20 to 40 mg daily. Median patient age was 40 years (range, 22 to 64 years). Seven of the 8 patients experienced complete subjective improvement in dysphagia symptoms at a maintenance dose of 20 to 40 mg daily. The eighth patient experienced moderate improvement at a dose of 30 mg but could not tolerate further titration due to myalgia and nausea. No relapse of eosinophilic esophagitis symptoms was reported while montelukast was administered; however, 6 patients experienced a recurrence in symptoms within 3 weeks of montelukast cessation or dosage reduction. Montelukast did not affect the density of esophageal eosinophils. Adverse reactions included nausea and myalgia.1
Noncontrolled Trial
A prospective review of 11 adult patients with eosinophilic esophagitis evaluated the efficacy of montelukast in maintaining clinical and histopathological remission achieved after administration of topical corticosteroids. Montelukast (10 mg daily) was administered for 3 months following a 6-month treatment course with fluticasone propionate (400 mcg twice daily). Intraepithelial and lamina propria mean eosinophil densities were significantly reduced following topical fluticasone propionate administration (from 54.38 to 1.8 cells per HPF [p = .003] and from 17.02 to 3.27 cells per HPF [p = .043], respectively); however, mean density of epithelial eosinophils was significantly increased, nearly reaching baseline levels, following montelukast treatment (50.96 cells per HPF [p = .003]). Lamina propia mean eosinophil density was not significantly increased following montelukast treatment (6.02 cells per HPF [p = .225]). Mean symptom score was significantly reduced from baseline following topical fluticasone propionate administration (p = .003). Mean symptom score increased following montelukast therapy (p = .003) but remained significantly lower than baseline scores (p = .005). The authors concluded that montelukast is not effective in maintaining clinical and histological improvements achieved by topical fluticasone.2
RISK/BENEFIT CONSIDERATIONS
This is a limited safety profile. Refer to package labeling for complete prescribing information (eg, Warnings/Precautions, Adverse Reactions, Drug Interactions).
Nausea and myalgia have been reported with use of montelukast for the management of eosinophilic esophagitis.1
Footnotes
Consulting Pharmacist, Pasco, Washington
REFERENCES
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