Cost-minimizing alternative dosage regimens of imipenem/cilastatin/relebactam for patients with renal impairment: a pharmacokinetic/pharmacodynamic simulation study.

PURPOSE: Renal function significantly influences the pharmacokinetics of imipenem/cilastatin/relebactam (IMI/REL). The standardized single-dose packaging commonly leads to considerable drug wastage when the medication is administered to patients with renal impairment. This investigation aimed to develop and assess alternative dosage regimens that optimize drug utilization and minimize waste.

METHODS

Through Monte Carlo simulations, we evaluated alternative regimens involving extended dosage intervals and prolonged infusion times across patients with various levels of renal impairment. We assessed probabilities of target attainment (PTA) against established pharmacokinetic/pharmacodynamic (PK/PD) targets and minimum inhibitory concentration (MIC) breakpoints, and evaluated the risk of drug overexposure. Additionally, we compared the alternative dosage regimens with standard regimens in terms of dose wastage and cost savings.

RESULTS

The findings suggest that administering full doses of IMI/REL every 8-12 h with prolonged infusion achieves satisfactory PTAs without significant overexposure risks. These alternative regimens are anticipated to reduce direct medical costs by $335.84 to $671.68 daily compared to standard dosages.

CONCLUSION

Alternative dosing regimens for IMI/REL in patients with renal impairment can optimize drug utilization, minimize waste, and provide significant cost savings. However, further clinical studies are necessary to validate the effectiveness and safety of these regimens.