OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Amifampridine – Generic, Firdapse®, Ruzurgi®

DRUG CLASS

Myasthenia Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Amifampridine	54-96-6	C5-H7-N3

ANNOTATED BIBLIOGRAPHY

References updated: 15 May 2019

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Textbook of hepatotoxicity published in 1999, before the availability of amifampridine, does not discuss myasthenic syndromes and their therapy).
• Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013.

  (Textbook of hepatotoxicity published in 2013, does not discuss amifampridine or other drugs for myasthenic syndromes).
• Taylor P. Anticholinesterase Agents. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 163-75.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/scripts/cder/daf/

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy; mentions that safety data were based upon 2 controlled withdrawal studies in 79 adults and that elevated liver enzymes occurred in 7 patients [13%], but all were self-limited and not accompanied by symptoms or jaundice).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to drugs used for myasthenic syndromes such as amifampridine).
• Verma S, Mazell SN, Shah DA. Amifampridine phosphate in congenital myasthenic syndrome. Muscle Nerve. 2016;54:809–10. [PubMed: 27348204]

  (Two children [ages 4 and 5 years] with congenital myasthenic syndromes associated with mutations in the acetylcholine receptor had improvements in clinical symptoms [ptosis, dysarthria, energy level] with amifampridine treatment [10-20 mg daily], with only minor side effects; no mention of ALT levels or hepatotoxicity).
• Burns TM, Smith GA, Allen JA, Amato AA, Arnold WD, Barohn R, Benatar M, et al. Editorial by concerned physicians: Unintended effect of the orphan drug act on the potential cost of 3,4-diaminopyridine. Muscle Nerve. 2016;53:165–8. [PubMed: 26662952]

  (Commentary by academic neurologists concerned about the approval of amifampridine [3,4-diaminopyridine] as an orphan drug for Lambert-Eaton myasthenic syndrome and the possible result of a very expensive therapy that would replace the reasonably priced compassionate use product).
• McEnany PJ. A response to a recent editorial by concerned physicians on 3,4-diaminopyridine. Muscle Nerve. 2017;55:138. [PubMed: 27756108]

  (Response to the commentary by Burns [2016] argues that the benefit of an FDA approved therapy for Lambert-Eaton syndrome far outweighs the possible negative effect of increase price).
• Schoser B, Eymard B, Datt J, Mantegazza R. Lambert-Eaton myasthenic syndrome (LEMS): a rare autoimmune presynaptic disorder often associated with cancer. J Neurol. 2017;264:1854–63. [PubMed: 28608304]

  (Review of the history of discovery, epidemiology, pathophysiology, clinical features, electromyographic findings, autoimmune serology, diagnosis, management and therapy of Lambert-Eaton myasthenic syndrome; mentions that amifampridine may be effective for its symptomatic treatment [increasing neurotransmission] but that immunosuppressive therapy is needed to decrease disease progression).
• Sanders DB, Juel VC, Harati Y, Smith AG, Peltier AC, Marburger T, Lou JS, et al. Dapper Study Team. 3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia. Muscle Nerve. 2018;57:561–8. [PMC free article: PMC5900968] [PubMed: 29280483]

  (Among 32 adults with Lambert-Eaton myasthenia on compassionate use 3,4-diaminopyridine who were either continued on treatment or switched to placebo for at least 3 months, objective measurements of myasthenic symptoms worsened in those who were withdrawn and not in those who continued on therapy, and “there were no clinically meaningful laboratory value changes”).
• Bonanno S, Pasanisi MB, Frangiamore R, Maggi L, Antozzi C, Andreetta F, Campanella A, et al. Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a phase IIb, randomized, double-blind, placebo-controlled, double crossover study. SAGE Open Med. 2018;6:2050312118819013. [PMC free article: PMC6299310] [PubMed: 30574306]

  (Among 10 patients with muscle-specific kinase myasthenia gravis who were treated with amifampridine or placebo in a double-cross over study, myasthenia symptoms improved on amifampridine and deteriorated on placebo, and the only drug-specific adverse event was transient paresthesia; there were “no relevant differences between the two groups for…blood chemistries…over the duration of the study”).