Eosinophilic Pneumonia and Extended-Release Injectable Naltrexone

Abstract

Extended-release injectable naltrexone is an opioid antagonist approved for the treatment of alcohol and opioid dependence. Since the release of the drug in 2006, a literature review reveals five reported cases of drug-induced eosinophilic pneumonia. Our case highlights the clinical presentation of drug-induced eosinophilic pneumonia in the setting of extended-release injectable naltrexone. CASE PRESENTATION:A 35-year-old female with a past medical history lifelong tobacco use and alcohol dependence on extended-release injectable naltrexone presented to the ED with subjective fevers, myalgias, cough, and pleuritic chest pain. She was evaluated at urgent care two days prior and sent home on a course of Levofloxacin for bronchitis. Upon ED arrival, she was noted to be hypoxic and placed on supplemental oxygen. She was afebrile and tachycardic. Exam was pertinent for tachypnea and bilateral crackles. Initial laboratory data revealed WBC 19,500 (neutrophil predominate) and lactic acid 1.4. Chest x-ray and chest CT demonstrated extensive bilateral infiltrates. Empiric antibiotics were initiated while awaiting microbiology data. Due to escalating oxygen requirements and hemodynamic instability over the next 24 hours, the patient was intubated and bedside bronchoscopy was completed. BAL studies revealed lymphocyte predominance (46%) followed by eosinophils (27%) and neutrophils (21%). Given concern for acute eosinophilic pneumonia in the setting of extended-release injectable naltrexone, corticosteroids were started. Antibiotics were discontinued given negative culture data and our patient showed marked clinical improvement with continuation of steroid therapy.DISCUSSION: Extended-release injectable naltrexone is a long-acting opioid antagonist approved for the treatment of alcohol dependence. Clinical trials showed one diagnosed case & one suspected case of naltrexone-induced eosinophilic pneumonia. A current medical literature review reveals a paucity of cases associated with naltrexone and drug-induced AEP. While the etiology & pathogenesis remain largely unknown, it is thought to be related to an acute hypersensitivity reaction to an antigen in a genetically susceptible person. Progression from mild dyspnea to overt respiratory failure is rapid. Initial diagnostics are often nonspecific, however pleural fluid analysis demonstrates striking eosinophilia (10%-50%) and BAL fluid classically shows marked eosinophilia (25%-55%). Treatment includes supportive care, withdrawal of any eliciting medications, and glucocorticoid therapy. Most patients rapidly improve within 12-48 hours of initiation of corticosteroids. The prognosis for acute eosinophilic pneumonia is excellent with the vast majority of patients enjoying complete recovery.CONCLUSIONS: This case highlights the rare but important association between drug-induced eosinophilic pneumonia and extended-release injectable naltrexone.

A case of naltrexone-induced acute eosinophilic pneumonia

“…She was found to have bilateral ground-glass opacities on CT of the chest and 27% eosinophils on BAL fluid. Steroids were initiated with rapid improvement 16. The fifth case was in 2022 when a middle-aged man presented with rapidly progressive respiratory failure post-naltrexone.…”

“…She was empirically treated with high-dose steroids given high concern for AEP and rapidly recovered 17. While all these cases share features of AEP including rapidly progressive respiratory failure after Vivitrol injection, with bilateral infiltrates on imaging and BAL eosinophilia, interestingly, not all patients developed it after first injection and some had it after second or third injection, raising concern for occurrence of this pneumonia even later in the course 3–6 8 16 17…”