RESUMO
PURPOSE: This review aims to provide an update on current pharmacological agents for the management of generalized myasthenia gravis (MG). SUMMARY: MG is an autoimmune disease characterized by impaired neuromuscular transmission and muscle weakness. Most patients have autoimmune antibodies to the nicotinic acetylcholine receptor, with treatments aimed at eliminating or decreasing levels of autoantibodies. Limitations of current treatments for generalized MG include limited efficacy and serious adverse effects, indicating a continued need for new treatments. Efgartigimod alfa, a biologic newly approved by the Food and Drug Administration, provides a novel treatment option for patients with chronic generalized MG. CONCLUSION: While the landscape for treatment of generalized MG has expanded over recent years, there is still an unmet need for patients for whom multiple lines of treatment have failed. The introduction of neonatal Fc receptor antagonists such as efgartigimod alfa may have an immediate impact in patients for whom standard-of-care therapy has failed.
Assuntos
Miastenia Gravis , Estados Unidos , Recém-Nascido , Humanos , Adulto , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Receptores Colinérgicos/uso terapêutico , AutoanticorposRESUMO
PURPOSE: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results. Currently, two potential reversal agents for oral direct factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of clinical development. Idarucizumab, a reversal agent for the oral direct thrombin inhibitor dabigatran, was approved by FDA in October 2015. Idarucizumab and andexanet alfa have been reported to produce anticoagulation reversal effects within minutes of administration. Ciraparantag was demonstrated to decrease whole blood clotting time to within 10% of baseline values in 10 minutes or less, with a return to baseline hemostasis in 10-30 minutes. TSOAC reversal agents have been generally well tolerated in clinical trials. CONCLUSION: Idarucizumab and other TSOAC reversal agents, such as andexanet alfa and ciraparantag, present the potential for consistent and effective treatment and management options when life-threatening or uncontrolled TSOAC-associated bleeding occurs or when emergency surgery is warranted in patients using TSOACs.
Assuntos
Antitrombinas/farmacologia , Administração Oral , Antitrombinas/administração & dosagem , Antitrombinas/uso terapêutico , Dabigatrana/administração & dosagem , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Avaliação de Medicamentos , Hemorragia/prevenção & controle , Humanos , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/administração & dosagem , Piridinas/farmacologia , Piridinas/uso terapêutico , Piridonas/administração & dosagem , Piridonas/farmacologia , Piridonas/uso terapêutico , Rivaroxabana/administração & dosagem , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Tiazóis/administração & dosagem , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Estados Unidos , United States Food and Drug AdministrationRESUMO
Parenteral nutrition (PN) provides a means of nourishment for patients in whom oral or enteral nutrition is not possible or practical. Initial formulations consisted of carbohydrates (dextrose), amino acids, vitamins, trace minerals, electrolytes, and water. A stable intravenous fat emulsion (IVFE) permitted the combination of all 3 macronutrients in the same admixture (3-in-1 or total nutrient admixture [TNA]). Many institutions have adopted these TNAs as the standard formulation. Others, due to a variety of concerns (including historical concerns regarding stability), continue to administer PN as a formulation of dextrose and amino acids (2-in-1) with separate IVFE infusions. The aim of this article is to review the literature regarding the use of TNA vs 2-in-1 formulations. The published data were critically analyzed, and a preferred strategy was suggested based on an interpretation of the data. Concerns surrounding the safety of 2-in-1 vs 3-in-1 PN formulations can be grouped with respect to those regarding infections, emulsion instability ("cracking"), and precipitant formation. These concerns are largely historical and would seem to be no longer relevant to adult PN formulations. We believe that the available (limited) data support the safe transition to the 3-in-1 formulation as the standard of care in adult PN.