Subcutaneous furosemide in heart failure: a systematic review

Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, and ‘skin-friendly’ preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF.

The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 30 September 2024. Of the 17 studies identified, 5 were randomized controlled trials (RCTs), 2 were non-randomized controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.

All RCTs utilized novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10 mg/mL: 99.7% for an 8 mg/mL preparation and 112% for a 30 mg/mL preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events related to novel preparations included infusion site pain or discomfort, localized skin erythema and minimal swelling. All studies of subcutaneous conventional furosemide were non-randomized with very few data regarding bioavailability or diuretic and natriuretic effect. Subcutaneous conventional furosemide was associated with substantial skin irritation (affecting 3–23% of patients), and skin infections requiring treatment with antibiotics (3–17%).

Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.