Safety of add-on tolvaptan in patients with furosemide-resistant congestive heart failure complicated by advanced chronic kidney disease: a sub-analysis of a pharmacokinetics/ pharmacodynamics study.

BACKGROUND: Treatment of congestive heart failure (CHF) with loop diuretics, such as furosemide, may be associated with complications, including worsening renal function and metabolic or electrolyte disturbances. Coadministration of tolvaptan, a selective vasopressin V2 receptor antagonist, can ameliorate such adverse events by reducing the required dose of loop diuretics; however, the safety of tolvaptan in patients with reduced renal function is not known. As a result, we conducted an exploratory clinical trial of tolvaptan in 22 patients with CHF and advanced chronic kidney disease (CKD).

METHODS: We classified these patients into three groups according to their estimated glomerular filtration rate, namely, CKD stages G3b, G4, and G5. Patients were coadministered tolvaptan 15 mg once daily for 7 days after single administration of furosemide. We assessed patients' hemodynamic parameters, serum chemistry values, and body fluid status during the study.

RESULTS: On day 8, serum sodium and potassium concentrations were significantly higher than baseline values in the G3b (p=0.020) and G5 groups (p=0.037), respectively. Although serum urea nitrogen and creatinine concentrations increased significantly in the G4 group (p=0.017 and p=0.012, respectively), no patient in any of the three groups showed decreased renal function on days 2 and 3. In addition, no significant changes in serum uric acid, blood pressure, or heart rate were observed in any patient in this study.

CONCLUSION: In this short-term pilot study, coadministration of tolvaptan and furosemide appears to be safe in patients with heart failure and CKD.