OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Eravacycline	1207283-85-9	C29-H39-N5-O8

ANNOTATED BIBLIOGRAPHY

References updated: 10 April 2019

• Zimmerman HJ. Tetracyclines. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999. p. 599-602.

  (Expert review of tetracycline and liver injury published in 1999, long before the availability of eravacycline; the tetracyclines cause two forms of drug induced liver injury, microvesicular fat and liver failure occurring after 4-10 days with high doses of parenteral tetracyclines and an idiosyncratic liver injury that occurs with the oral agents, doxycycline causing a cholestatic and minocycline a hepatocellular injury which may be associated with autoimmune features).
• Moseley RH. Tetracyclines. Hepatotoxicity of antimicrobials and antifungal agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 468.

  (Expert review of tetracycline induced liver injury; mentions that the hepatotoxicity of intravenous tetracycline is of historic interest only as it is no longer given parenterally; both doxycycline and minocycline have been associated with idiosyncratic liver injury; tigecycline and eravacycline are not discussed).
• MacDougall C. Protein synthesis inhibitors and miscellaneous antibacterial agents. In, Brunton LL, Hilal-Dandan R, Knollman KC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1049-65.

  (Textbook of pharmacology and therapeutics).
• 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 the toxicity profile of eravacycline is consistent with other tetracycline-like antibiotics, and while ALT elevations above twice ULN arose in 9-20% of eravacycline treated subjects, these rates were no different than with comparator antibiotics–such as meropenem and ertapenem [10-19%] and no patient developed clinically apparent liver injury attributable to eravacycline).
• Solomkin JS, Ramesh MK, Cesnauskas G, Novikovs N, Stefanova P, Sutcliffe JA, Walpole SM, et al. Phase 2, randomized, double-blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections. Antimicrob Agents Chemother 2014; 58: 1847-54. [PMC free article: PMC4023720] [PubMed: 24342651]

  (Among 139 patients with intraabdominal infections treated with eravacycline [1.0 mg/kg every 12 hours or 1.5 mg/kg every 24 hours] vs ertapenem [1 g every 24 hours], clinical success rates were similar [100% and 93% vs 92%] and no “safety signals as evaluated by laboratory tests… were identified”).
• Zhanel GG, Cheung D, Adam H, Zelenitsky S, Golden A, Schweizer F, Gorityala B, et al. Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs 2016; 76: 567-88. [PubMed: 26863149]

  (Review of the structure, antibacterial spectrum of activity, pharmacology, clinical efficacy and safety of eravacycline; mentions that the most common adverse event is nausea and vomiting, but that other event rates are similar to those in comparator arm subjects; no discussion of ALT elevations or hepatotoxicity).
• Solomkin J, Evans D, Slepavicius A, Lee P, Marsh A, Tsai L, Sutcliffe JA, et al. Assessing the efficacy and safety of eravacycline vs ertapenem in complicated intra-abdominal infections in the investigating gram-negative infections treated with eravacycline (IGNITE 1) trial: a randomized clinical trial. JAMA Surg 2017; 152: 224-32. [PubMed: 27851857]

  (Among 541 patients with complicated intraabdominal infections treated with eravacycline [1 mg/kg every 12 hours] or ertapenem [1 gm every 24 hours] for 4-14 days, rates of clinical cure were similar [87% vs 88%] while adverse events were more frequent with eravacycline [42% vs 28%], although severe adverse event rates were similar [6% vs 5.6%]; no mention of ALT elevations or hepatotoxicity).
• Newman JV, Zhou J, Izmailyan S, Tsai L. Randomized, double-blind, placebo-controlled studies of the safety and pharmacokinetics of single and multiple ascending doses of eravacycline. Antimicrob Agents Chemother 2018; 62. pii: e01174-18. [PMC free article: PMC6201080] [PubMed: 30150464]

  (Pharmacokinetic studies in healthy subjects indicated that a 1 mg/kg dose of eravacycline was most appropriate and that it was generally well tolerated with dose related nausea, infusion site reactions and superficial phlebitis being the most common adverse events).
• Solomkin JS, Gardovskis J, Lawrence K, Montravers P, Sway A, Evans D, Tsai L. IGNITE4: Results of a phase 3, randomized, multicenter, prospective trial of eravacycline vs. meropenem in the treatment of complicated intra-abdominal infections. Clin Infect Dis 2018 Dec 18. [Epub ahead of print] [PMC free article: PMC6735687] [PubMed: 30561562]

  (Among 400 hospitalized patients with intraabdominal infections treated with eravacycline or meropenem intravenously for 4-14 days, clinical cure rates were similar [91% vs 91%], and adverse events included nausea [5%], vomiting [4%] and diarrhea [3%]; no mention of ALT elevations or hepatotoxicity).