Adjusting Eptifibatide Doses for Renal Impairment: A Model of Dosing Agreement Among Various Methods of Estimating Creatinine Clearance

BACKGROUND: Because of the renal elimination and increased risk for bleeding events at supratherapeutic doses of eptifibatide, the manufacturer recommends dosing adjustment in patients with renal dysfunction. Methods commonly used to estimate renal dysfunction in hospital settings may be inconsistent with those studied and recommended by the manufacturer. OBJECTIVE: To compare hypothetical renal dosing adjustments of eptifibatide using both the recommended method and several other commonly used formulas for estimating kidney function. METHODS: Sex, age, weight, height, serum creatinine, and estimated glomerular filtration rate (eGFR) were obtained retrospectively from the records of patients who received eptifibatide during a 12-month period. Renal dosing decisions were determined for each patient based on creatinine clearance (CrCl) estimates via the Cockcroft-Gault formula (CG) with actual body weight (ABW), ideal body weight (IBVV) or adjusted weight (ADJVV), and eGFR from the Modification of Diet in Renal Disease formula. Percent agreement and Cohen kappa were calculated comparing dosing decisions for each formula to the standard CG-ABW. RESULTS: In this analysis of 179 patients, percent agreement as compared to CG-ABW varied (CG-IBW: 90.50%, CG-ADJW: 95.53%, and eGFR: 93.30%). All kappa coefficients were categorized as good. In the 20% of patients receiving an adjusted dose by any of the methods, 68.6% could have received a dose different from that determined using the CG-ABW formula. CONCLUSIONS: In the patients with renal impairment (CrCl <50 mL/min) in this study, two thirds would have received an unnecessary 50% dose adjustment discordant from the manufacturer's recommendation. Because failure to adjust eptifibatide doses in patients with renal impairment has led to increased bleeding events, practitioners may be inclined to err on the side of caution. However, studies have shown that suboptimal doses of eptifibatide lead to suboptimal outcomes. Therefore, correct dosing of eptifibatide is important to both patient safety and efficacy.