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Australian Prescriber Oct 2022
Review
PubMed: 36382167
DOI: 10.18773/austprescr.2022.056 -
Expert Review of Clinical Immunology Oct 2019: The present status of amifampridine (AFP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) is reviewed. : All relevant literature identified through a... (Review)
Review
: The present status of amifampridine (AFP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) is reviewed. : All relevant literature identified through a PubMed search under treatment of LEMS, aminopyridine, and amifampridine are reviewed. An expert opinion on AFP was formulated. : 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.
Topics: Amifampridine; Cholinesterase Inhibitors; Drug and Narcotic Control; Guanidine; Humans; Lambert-Eaton Myasthenic Syndrome; Potassium Channel Blockers; Practice Guidelines as Topic; Randomized Controlled Trials as Topic
PubMed: 31533480
DOI: 10.1080/1744666X.2020.1670061 -
The Annals of Pharmacotherapy Jan 2020The 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... (Review)
Review
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. PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: , and . Completed trials were also reviewed at clinicaltrials.gov. 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. 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. With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.
Topics: Adult; Amifampridine; Databases, Factual; Fees, Pharmaceutical; Female; Humans; Lambert-Eaton Myasthenic Syndrome; Middle Aged; Neuromuscular Agents; United States; United States Food and Drug Administration
PubMed: 31319693
DOI: 10.1177/1060028019864574 -
Expert Review of Clinical Pharmacology Nov 2019: Lambert-Eaton myasthenic syndrome is an autoimmune disease of the neuromuscular junction characterized by a presynaptic defect of neuromuscular transmission resulting... (Review)
Review
: Lambert-Eaton myasthenic syndrome is an autoimmune disease of the neuromuscular junction characterized by a presynaptic defect of neuromuscular transmission resulting in muscle weakness and fatigability. Diagnostic features are specific neurophysiological alterations and autoantibody detection. The present review is focused on the use of Amifampridine Phosphate to treat LEMS patients.: Medline search from 1990 to 2019 was examined using the free subject terms: Lambert-Eaton myasthenic syndrome, LEMS, Amifampridine, 3,4-diaminopyridine, which were then combined with Treatment, Therapy, Clinical Trial, Controlled Clinical Trial, Randomized Clinical Trial and Cochrane Review. The author has done a supervised analysis of the retrieved articles and focused on those subjectively evaluated as most relevant.: Data from randomized clinical trials and case series have demonstrated that Lambert-Eaton myasthenic syndrome symptoms were successfully treated by Amifampridine Phosphate. Hence, the drug represents a substantial step forward in the symptomatic treatment of the disease due to its efficacy, safety and reliable GMP formulation. As Amifampridine Phosphate works by enhancing the release of acetylcholine at the neuromuscular junction by blocking K+ efflux at the pre-synaptic membrane, it is also conceivable to use it for other diseases of the neuromuscular junction in which such an effect is searched for.
Topics: Amifampridine; Humans; Lambert-Eaton Myasthenic Syndrome; Neuromuscular Agents; Potassium Channel Blockers; Randomized Controlled Trials as Topic; Tablets
PubMed: 31639317
DOI: 10.1080/17512433.2019.1681972 -
Drugs of Today (Barcelona, Spain : 1998) Oct 2020Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disabling neuromuscular disease caused by antibodies against presynaptic voltage-gated calcium...
Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disabling neuromuscular disease caused by antibodies against presynaptic voltage-gated calcium channels. It reduces the quantal release of acetylcholine (Ach), causing muscle weakness, reduced or absent reflex and dysautonomia. About half of LEMS patients have associated small cell lung cancer. For symptomatic treatment, amifampridine (3,4-diaminopyridine [3,4-DAP]) is ideal because it increases the release of Ach at the presynaptic membrane. Since the first use of 3,4-DAP in LEMS patients in the 1980s, 136 LEMS patients were treated with amifampridines in the open-label studies and 208 patients in the eight randomized studies. These studies showed that amifampridine is the most effective drug for symptomatic treatment in LEMS. Now, 3,4-DAPP (3,4-DAP phosphate) is approved for adult LEMS patients and 3,4-DAP for pediatric patients. The recommended dose is 80 mg a day, divided 3 or 4 times a day. Side effects are usually mild, and the most frequently reported are paresthesia.
Topics: Adult; Amifampridine; Child; Humans; Lambert-Eaton Myasthenic Syndrome; Lung Neoplasms; Small Cell Lung Carcinoma
PubMed: 33185628
DOI: 10.1358/dot.2020.56.10.3137144 -
Current Opinion in Rheumatology Nov 2019This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and... (Review)
Review
PURPOSE OF REVIEW
This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs.
RECENT FINDINGS
Novel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients.
SUMMARY
CBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.
Topics: Autoantibodies; Biological Factors; Electromyography; Humans; Immunosuppressive Agents; Myasthenia Gravis; Treatment Outcome
PubMed: 31385879
DOI: 10.1097/BOR.0000000000000647