title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  In this short-term pilot study, coadministration of tolvaptan and furosemide appears to be safe in patients with heart failure and CKD.
authors.forename: Naoto
authors.initials: N
authors.lastname: Tominaga
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kida
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Yoshihiro J
authors.initials: YJ
authors.lastname: Akashi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Miyake
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shibagaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000009:adverse effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D000077602:Tolvaptan; D014527:Uric Acid / Q000097:blood
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D014527:Uric Acid; D005665:Furosemide; D003404:Creatinine