Daptomycin Dosage Optimization in Renal Impairment Using Model-Informed Precision Dosing.

BACKGROUND: Daptomycin's efficacy and toxicity are closely related to its exposure, which can vary widely among individuals. The patient, a 59-year-old male with an estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73 m² and a weight of 64 kg, was treated with 850 mg of daptomycin every other day for infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). For patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m², the dosing recommendations are not explicitly defined in the endocarditis guidelines. Subsequently, the pharmacology department was contacted to adjust the dosage. METHODS: A population pharmacokinetic model developed by Dvorchik et al. was used for Bayesian estimation of the patient's pharmacokinetic parameters. The 24-hour area under the curve (AUC24) of daptomycin was calculated at steady state using peak and trough plasma samples. RESULTS: The minimum inhibitory concentration (MIC) of the MRSA strain was 0.25 mg/L. An AUC24/MIC ratio below 666 is associated with higher mortality risk, while an AUC24 above 939 h·mg/L correlates with increased risk of muscular toxicity. Initial AUC24 estimation was 1091 h·mg/L. Following a dosage reduction to 700 mg every other day, the AUC24 increased to 1600 h·mg/L. Further reduction to 500 mg every other day brought the AUC24 down to 750 h mg/L, with two subsequent measurements showing consistent AUC24 values of 500 h·mg/L, which is within the target range. CONCLUSIONS: Daptomycin ended 6 weeks after the initial negative blood culture, with no adverse effects or recurrence of MRSA infection. This case underscores the need for therapeutic drug monitoring and a multidisciplinary approach to adjust daptomycin doses in patients with renal impairment.

Synergizing pharmacometrics and pharmacovigilance for medication error management: the case of secukinumab.

PURPOSE: To demonstrate the effective integration of pharmacometrics and pharmacovigilance in managing medication errors, highlighted by a case involving secukinumab in a patient with hidradenitis suppurativa. METHODS: We present the case of a 41-year-old male with progressive hidradenitis suppurativa, unresponsive to multiple antibiotic regimens and infliximab treatment. Due to a medication error, the patient received 300 mg of secukinumab daily for 4 days instead of weekly, totaling 1200 mg. The regional pharmacovigilance center assessed potential toxicity, and a pharmacometric analysis using a population pharmacokinetic model was performed to inform dosing adjustments. RESULTS: Clinical data indicated that the received doses were within a non-toxic range. No adverse effects were observed. Pharmacometric simulations revealed a risk of underexposure due to the dosing error. Based on these simulations, it was recommended to restart monthly secukinumab injections on day 35 after the initial dose. Measured plasma concentrations before re-administration confirmed the model's accuracy. CONCLUSION: This case highlights the crucial collaboration between clinical services, pharmacovigilance, and pharmacometrics in managing medication errors. Such interdisciplinary efforts ensure therapeutic efficacy and patient safety by maintaining appropriate drug exposure levels.