An updated vancomycin dosing protocol for initiating therapy in patients undergoing intermittent high-flux hemodialysis

Abstract

Purpose: To design an updated vancomycin dosing protocol for initiating therapy in patients undergoing chronic intermittent high-flux hemodialysis (iHFHD) that is congruent with the revised 2020 consensus guidelines for therapeutic drug monitoring (TDM).

Methods: Monte Carlo simulation methods were used to study vancomycin dosing for patients on iHFHD. Vancomycin regimens were constructed as intravenous infusions (for intradialytic administration) of a loading dose and maintenance doses 3 times weekly during subsequent dialysis sessions. Vancomycin plasma concentrations were simulated, and the probability of target attainment (PTA) for a 24-hour area under the time-concentration curve (AUC24) of 400 to 700 mg · h/L was determined. Standardized weight-based (ie, dose-banding) regimens were investigated, and an optimized protocol was selected based on TDM target attainment and practical considerations for use in the dialysis setting.

Results: The proposed vancomycin dosing protocol (for intradialytic administration) specifies 3 regimens: (1) a 1,500-mg loading dose and 750-mg maintenance doses for patients weighing 50 kg to 69 kg; (2) a 2,000-mg loading dose and 1,000-mg maintenance doses for patients weighing 70 kg to 89 kg; and (3) a 2,500-mg loading dose and 1,250-mg maintenance doses for patients weighing 90 kg to 110 kg. In a simulated hemodialysis population (n = 5,000), the proposed protocol delivered median (interquartile range [IQR]) loading and maintenance doses of 25.0 (23.4-26.6) mg/kg and 12.5 (11.8-13.3) mg/kg, respectively. The PTA for an AUC24 of 400 to 700 mg · h/L was 74.7% on day 1 and 70.8% on day 8, with less than 10% of values exceeding the target range.

Conclusion: Our proposed dosing protocol for patients undergoing iHFHD offers an updated and practical approach for initiating vancomycin therapy that can be optimized with early TDM.

Keywords: AUC; hemodialysis; pharmacodynamics; pharmacokinetics; therapeutic drug monitoring; vancomycin.