title: Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia.
abstract: OBJECTIVE
  The effect of loading dose and formulation on the safety and efficacy of conivaptan in the treatment of euvolemic and hypervolemic hyponatremia was studied.
  
  
  METHODS
  This parallel-group study randomized 121 hospitalized patients with euvolemic or hypervolemic hyponatremia to one of four treatment regimens: placebo loading dose followed by conivaptan continuous i.v. infusion using the ampul formulation (regimen 1), conivaptan loading dose followed by continuous i.v. infusion using the ampul formulation (regimen 2), placebo loading dose followed by conivaptan continuous i.v. infusion using the premixed formulation (regimen 3), or conivaptan loading dose followed by continuous i.v. infusion using the premixed formulation (regimen 4). The primary variable was the incidence and severity of injection-site reactions (ISRs), as evaluated using the ISR modified 5-point scale (ISRMS). Secondary outcomes included effects on serum sodium concentration (SSC), duration of effect, and safety and tolerability.
  
  
  RESULTS
  All four dosing regimens were efficacious, safe, and well tolerated. No significant differences in ISRMS scores or differences in changes from baseline SSC or in the duration of effects on SSC were observed between the regimens. Overly rapid SSC increases occurred in 7%, 7%, 3%, and 21% of patients treated with regimens 1, 2, 3, and 4, respectively. Overall, adverse events related to general disorders and ISRs occurred in 39%, 43%, 53%, and 55% of patients receiving regimens 1, 2, 3, and 4, respectively.
  
  
  CONCLUSIONS
  Intravenous conivaptan regimens with or without a loading dose, whether using the ampul or a premixed formulation, had similar safety, tolerability, and efficacy in patients with euvolemic or hypervolemic hyponatremia. The pre-mixed formulation used with a loading dose may be associated with an increased frequency of overly rapid increase in SSC compared with the other regimens studied.
authors.affiliation: Bharti Hospital and Bharti Research Institute of Diabetes and Endocrinology, Karnal, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kalra
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
authors.forename: John M
authors.initials: JM
authors.lastname: Arthur
authors.forename: Arie
authors.initials: A
authors.lastname: Oliven
authors.forename: Juan Carlos Q
authors.initials: JC
authors.lastname: Velez
authors.forename: Bruce E
authors.initials: BE
authors.lastname: McNutt
authors.forename: Sally
authors.initials: S
authors.lastname: Klasen
authors.forename: Anura
authors.initials: A
authors.lastname: Abeyratne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007010:Hyponatremia / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001552:Benzazepines; C106389:conivaptan