Evaluation of Severe Myalgia Induced by Continuous-Infusion Bumetanide in Patients with Acute Heart Failure

Abstract

Study objectives: Continuous intravenous (IV) infusion bumetanide has been associated with severe myalgia in case reports, and the package labeling lists a reported incidence of 0.2% for severe myalgia. The primary objective of this study was to quantify the incidence of bumetanide infusion-induced severe myalgia in patients with acute heart failure (AHF). Secondary objectives were to assess a dose-response relationship between bumetanide infusion rate and occurrence of myalgia and to investigate potential risk factors associated with bumetanide-induced myalgia.

Design: Retrospective analysis.

Setting: Large academic medical center.

Patients: Adults hospitalized with AHF who required bumetanide (≥ 0.5 mg/hr [464 patients]) or furosemide (≥ 20 mg/hr [197 patients]) by continuous IV infusion between September 2015 and May 2017.

Measurements and main results: The incidence of severe myalgia with IV furosemide infusion was assessed to measure confounding by indication bias. Electronic medical records were used to identify patients exposed to bumetanide 0.25-mg/ml or furosemide 2-mg/ml continuous IV infusions. We defined severe myalgia as a diffuse myalgia with a physician's documented suspicion of bumetanide- or furosemide-induced myalgia unresponsive to electrolyte repletion and necessitating a change to alternative diuretics. The incidence of severe myalgia during bumetanide therapy was 5.8%, with the incidence increasing with higher bumetanide infusion rates: 2.6% for an infusion rate ≤ 1 mg/hour and 10.3% for a rate > 1 mg/hour (p=0.0005). In the multivariate logistic regression analysis, a bumetanide infusion rate > 1 mg/hour was independently associated (odds ratio 4.8, 95% confidence interval 1.94-12.02, p=0.0007) with severe myalgia compared to that with a rate ≤ 1 mg/hour. No patients receiving furosemide continuous IV infusion experienced severe myalgia, although infusion rates were lower in potency than bumetanide infusion rates.

Conclusion: The incidence of severe myalgia in patients with AHF receiving bumetanide infusion was 5.8%, 29-fold higher than incidence rate listed in the package labeling. Patients receiving infusion rates > 1 mg/hour were 4-fold more likely to experience bumetanide-induced severe myalgia than those receiving rates ≤ 1 mg/hour.

Keywords: adverse event; bumetanide; heart failure; myalgia.