Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis

Abstract

Background: The Aveed Risk Evaluation and Mitigation Strategy program was instituted because of potential risk of pulmonary oil microembolism (POME) and/or anaphylaxis after intramuscular injection of Aveed (testosterone undecanoate), indicated for treatment of adult male patients with congenital or acquired primary hypogonadism or hypogonadotropic hypogonadism. Aim: To analyze the reporting rate of POME associated with testosterone undecanoate administration (750 mg/ 3 mL) during postmarketing surveillance. Methods: The Endo Pharmaceuticals Inc database was searched for POME reports occurring from testosterone undecanoate approval on March 5, 2014, through June 30, 2018. Each case was reviewed and adjudicated by a drug safety physician to confirm the reported event had predefined clinical characteristics consistent with POME. Outcomes: Annual rate and clinical features of spontaneously reported POME cases were characterized. Results: During the 4.3-year period, 90,092 doses of intramuscular testosterone undecanoate were distributed via an Aveed Risk Evaluation and Mitigation Strategy program to health-care professionals for patient treatment. Of 633 individual case safety reports in the Endo Pharmaceuticals Inc safety database, 28 spontaneously reported adverse events were classified as POME, for a yearly spontaneously reported adverse event per-injection rate of <0.1%. Most (21/22) events resolved, and of those with a resolution time reported, most (13/17) resolved in 30 minutes. More than 60% (13/21) of patients required no medical intervention (ie, the POME event resolved spontaneously). One fatality was reported 18 months after a documented POME event and appeared unrelated to the reported testosterone undecanoate injection or subsequent injections after the POME event. In 3 out of 4 POME cases with symptoms serious enough to require an emergency room visit, issues with injection technique or dosing were identified as a potential contributing factor. Clinical Implications: Injection technique and proper product usage are key elements in the prevention of POME events. Strengths & Limitations: The reported rate of POME events was determined from a real-world clinical practice patient population; however, postmarketing safety data typically are underreported and retrospective in nature. Conclusion: POME events appear to be rare, with resolution occurring quickly without medical intervention in most cases.

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