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.