From Oral to Subcutaneous Furosemide: The Road to Novel Opportunities to Manage Congestion.

The steadily rising prevalence of heart failure (HF) and the associated increase in health care expenditures represent a significant burden for patients, caregivers, and society. Ambulatory management of worsening congestion is a complex undertaking that requires diuretic escalation, yet clinical success is often hindered by the progressively declining bioavailability of oral agents. Once beyond a threshold, patients with acute on chronic HF often require hospital admission for intravenous diuresis. A novel, pH neutral formulation of furosemide that is administered by a biphasic drug delivery profile (80 mg total over 5 ​hours) via an automated, on-body infusor was designed to overcome these limitations. Early studies have shown that it has equivalent bioavailability with comparable diuresis and natriuresis to the intravenous formulation, leads to significant decongestion, and improvement in quality of life. It was shown to be safe and is well tolerated by patients. Although there is one ongoing clinical trial, available data have demonstrated the potential to shift hospital-administered, intravenous diuresis to the outpatient setting. Reduction in the need for recurrent hospital admissions would be highly desirable by most patients with chronic HF and would lead to a significant reduction in health care expenditures. In this article, we describe the rationale and evolution of this novel PH neutral formulation of furosemide administered subcutaneously, summarize its pharmacokinetic and pharmacodynamic profiles, and review emerging clinical trials demonstrating its clinical safety, efficacy, and potential to reduce health care expenditures.