Subcutaneous Furosemide Bioequivalent to IV, Bioavailable Across Multiple Injection Sites

Subcutaneous furosemide administration has achieved bioequivalence to intravenous (IV) furosemide for patients with heart failure (HF), according to new research.^1,2

These data were first revealed in a pair of presentations at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 in Phoenix, Arizona, by Alice Chan, DNP, and Barbara Cornelius, MS, respectively, from parent company MannKind. In an interview with HCPLive, Tochi Okwueze, DNP, supervisor and advanced heart failure provider at the heart failure clinic with Ascension Medical Group, discussed the results of these studies and their implications for the future of HF treatment with furosemide.^1,2

“Prior studies have already proven themselves in the clinically ill patient, the class 3 patient with the original on-body infuser, so we have the data and the information from that study,” Okwueze told HCPLive. “Now that they’ve transitioned to the autoinjector, it’s just a matter of proving the route as well as that the medication is getting absorbed.”

Prior studies had already fully established subcutaneous furosemide’s bioequivalence to IV furosemide. The first of 2 studies, therefore, instead focused on the bioavailability of subcutaneous furosemide administered in the thigh and upper arm. This was an open-label, single-center, single-dose randomized 3-way crossover study in which patients were randomly assigned in a 1:1:1 ratio to either IV furosemide, subcutaneous furosemide in the thigh, or subcutaneous furosemide in the upper arm. The IV treatment was given as 2 40 mg boluses 2 hours apart, while the subcutaneous version was administered as 80 mg over 10 seconds.¹

Chan and colleagues collected plasma concentrations, urine output, and urinary sodium excretion for 8 hours post-dose, and relative bioavailability was assessed using geometric mean ratios for AUClast and AUCinf, with BE defined if 90% Cis were within 80-125%. Over the course of the study, patients in each arm were crossed over to the other treatment methods, with a washout period of 7 +/- 1 days between each treatment.¹

A total of 19 patients were enrolled in the trial, and 17 were evaluable for the analysis. Subcutaneous furosemide achieved bioequivalence relative to IV furosemide at both sites, with a mean relative bioavailability of 91.3% (90% CI, 86.3-96.6) in the thigh group and 92.7% (90% CI, 88.3-97.2) in the upper arm group. Absorption was slower for subcutaneous furosemide, and mean urine output and sodium excretion were similar across the arms. Cumulative urine output and sodium excretion increased rapidly over 3 hours and plateaued at around hour 6 after treatment.¹

The other presentation, meanwhile, compared furosemide 80 mg/10 mL to MannKind’s investigative 80 mg/mL formulation, which is administered subcutaneously as a single 5-10-second injection. This was a set of 2 randomized, open-label crossover studies, the first of which compared IV furosemide to either the 5-hour subcutaneous infusion or subcutaneous injection. The infusion study enrolled patients with New York Heart Association (NYHA) class 2 or 3 heart failure, while the injection study enrolled healthy patients.²

A total of 15 patients completed the infusion study and 19 completed the injection study. IV dosing ultimately produced mean Cmax values roughly 4-fold (infusion) and 2-fold (injection) higher than subcutaneous dosing, while area under the curve values remained similar. This confirmed bioequivalence among the 2 formulations. Urine output onset occurred within the first hour for both subcutaneous injection and infusion, but the volume was greater in the injection arm. 8-hour urine output and sodium excretion were comparable across all 3 arms.²

Ultimately, these 2 presentations confirmed both the bioequivalence of subcutaneous furosemide with IV furosemide and the bioavailability of a set of alternate injection sites. Taken together, these data reflect an entirely separate pathway for treatment in patients with heart failure who are unable to achieve diuresis.^1,2

“Having the opportunity to have multiple routes under administration not only gives the patient the ability to rotate sites if and when they choose to, but if they have other devices that are placed in their abdominal area, it gives them a bit of an out to be able to use their arms or their thighs as an alternate route,” Okwueze said. “This, along with the fact that it has almost 100% bioavailability, makes it a great alternative.”

Editors’ Note: Okwueze reports no relevant disclosures.

References

1. Nguyen D, Cornelius B, Kamineni P, et al. Subcutaneous (SC) Injection of Furosemide: Consistent Pharmacokinetic and Pharmacodynamic Profiles Across Thigh And Arm Injection Sites Versus Intravenous Administration When Administered Via An Autoinjector. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.

2. Cornelius B, Kamineni P, Goodwin M, et al. Pharmacokinetics (PK) and Pharmacodynamic (PD) Profiles of Subcutaneous Furosemide (FUR SC) Administered as a 5-hour Infusion and 10-second Injection. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.