Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Apr 2021
Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database.
Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) and authorized conditionally by the European Medicines Agency (EMA) for patients with coronavirus disease 2019 (COVID-19). Its benefit-risk ratio is still being explored because data in the field are rather scant. A decrease of the creatinine clearance associated with remdesivir has been inconstantly reported in clinical trials with unclear relevance. ⋯ ROR of ARF with remdesivir was 20-fold (20.3; confidence interval 0.95 [15.7-26.3], P < 0.0001]) that of comparative drugs. Based on ARF cases reported in VigiBase, and despite the caveats inherent to COVID-19 circumstances, we detected a statistically significant pharmacovigilance signal of nephrotoxicity associated with remdesivir, deserving a thorough qualitative assessment of all available data. Meanwhile, as recommended in its Summary of Product Characteristics, assessment of patients with COVID-19 renal function should prevail before and during treatment with remdesivir in COVID-19.
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Clin. Pharmacol. Ther. · Apr 2021
ReviewKey Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock.
Early initiation of effective antibiotic therapy is vitally important for saving the lives of critically ill patients with sepsis or septic shock. The susceptibility of the infecting pathogen and the ability of the selected dosage regimen to safely achieve the required antibiotic exposure need to be carefully considered to achieve a high probability of a successful outcome. Critically ill patients commonly experience substantial pathophysiological changes that impact the functions of various organs, including the kidneys. ⋯ Two common conditions that very substantially complicate the use of antibiotics in critically ill patients with sepsis, unstable renal function, and augmented renal clearance, are considered in detail and their potential therapeutic implications are explored. Suggestions are provided on how treatment of bacterial infections in critically ill patients with sepsis might be improved. Of high potential are model-informed approaches that aim to individualize initial treatment regimens based on patient and bacterial characteristics, with refinement of regimens during treatment in response to monitoring antibiotic concentrations, responsive measures of renal function, and other important clinical data.