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Background: The nonmedical abuse of prescription opioids via intranasal administration is a growing problem. The objective of this study is to investigate of the typical presentation of intranasal opioid-acetaminophen abuse and outline optimal therapy., Methods: This study was a retrospective chart review. Patients with intranasal pathology from inhalation of combined opioid-acetaminophen medications (COAMs) from 3 academic otolaryngology practices in western Pennsylvania from January 2012 to October 2012 were included in the review., Results: Seven adults ranging in age from 23 to 46 years were identified with nasal complaints from the intranasal inhalation of COAMs. All patients presented with nasal pain and were found to have fibrinous necrotic nasal mucosa involving the posterior nasal cavity and nasopharynx. Of the 7 patients, 6 (85.7%) presented with a septal perforation. Pathology and culture revealed fungus in 85.7% of the patients; however, no invasive fungal disease was noted in any of the specimens. Patients did not improve with either systemic or topical antifungal therapy. Polarizable material characteristic of talc used as a tablet binder was present in the histopathology of 4 of 7 (57.1%) patients. Patients who abstained from intranasal drug use along with serial debridement demonstrated the greatest improvement., Conclusion: Intranasal COAM abuse causes nasal pain, tissue necrosis with potential septal and palatal perforation, and noninvasive fungal colonization. Antifungal therapy was of no benefit in the current series of patients. Current therapy should focus on recognition of the etiology of patients' pathology and encourage abstinence from intranasal use of these drugs along with serial debridements., (© 2014 ARS-AAOA, LLC.)