Pharmacotherapy
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Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. ⋯ No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).
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Lefamulin is a novel pleuromutilin recently approved by the FDA for the treatment of community-acquired bacterial pneumonia. Given that, lefamulin is primarily metabolized by CYP450 Phase-1 reactions, this study evaluated the pharmacokinetics of IV lefamulin in subjects with various degrees of hepatic impairment as compared with matched healthy subjects. ⋯ Lefamulin was generally well tolerated. Differences in lefamulin and BC-8041 pharmacokinetics were small, relative to the overall variability, and any changes appear to be compensated by increases in renal clearance and decreased protein binding.
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Lefamulin is a novel IV and oral pleuromutilin recently approved for the treatment of community-acquired bacterial pneumonia (CABP). Given that renal comorbidities are common in patients admitted for CABP, understanding the pharmacokinetics of lefamulin in the face of severe renal impairment, including those requiring hemodialysis, is needed. ⋯ No dosage adjustment is required for patients with renal impairment, and lefamulin can be administered without regard to hemodialysis timing.