Objective: The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Data Synthesis: Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.
Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism (VTE). Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists, limitations to their use still exists, leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors. To date, 3 target-specific oral anticoagulants (TSOACs) are Food and Drug Administration approved; several other agents are currently in development to optimize VTE management and minimize bleeding risks. The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE. Of the agents in development, edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents. Clinicians should understand the TSOACs under investigation, since differences in pharmacokinetics and pharmacodynamics may influence clinical decision making and agent selection for management of VTE. Currently, no direct comparisons between TSOACs have been conducted. Agents under investigation have yet to overcome the major limitations of the currently existing TSOACs. Further studies are necessary to clarify which TSOAC agent is best for management of VTE in clinical practice.
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