Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug.

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.

Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome.

Introduction: The present status of amifampridine (AFP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) is reviewed. Areas covered: All relevant literature identified through a PubMed search under treatment of LEMS, aminopyridine, and amifampridine are reviewed. An expert opinion on AFP was formulated. Expert opinion: AFPs, 3,4-DAP and 3,4-DAPP, are the most studied drugs in neuromuscular diseases. Randomized and non-randomized studies showed the most effective drug as symptomatic medication for LEMS. AFPs are safe and tolerable. Thus, AFPs should be the drug of choice for the symptomatic treatment in LEMS. As long as the daily dose is less than 80 mg a day, there is no concern for the serious side-reaction, seizure. Because of short-acting drug effects, it should be given three or four times a day. Peri-oral and finger paresthesia, the most common side-reaction, is accepted as a sign of drug-intake by many patients. Gastro-intestinal side reactions, the next common side-reaction of AFPs, are tolerable. AFPs are also the drug of choice and life-saving for LEMS crisis. For the long-term usage, it is proven to be safe and AFPs can be supplemented with liberal amount of pyridostigmine to sustain a symptomatic improvement without any undue side-reaction.