Purpose: 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.
Conclusion: 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.