OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Delafloxacin – Baxdela®

DRUG CLASS

Antiinfective Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Delafloxacin Meglumine	352458-37-8	C18-H12-Cl-F3-N4-O4.C7-H17-N-O5

ANNOTATED BIBLIOGRAPHY

References updated: 10 March 2020

• Zimmerman HJ. Quinolones. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999. p 603.

  (Expert review of hepatotoxicity published in 1999; mentions that cinoxacin, nalidixic acid, ciprofloxacin, norfloxacin, enoxacin, and ofloxacin are associated with minor serum enzyme elevations during therapy and with rare instances of clinically apparent liver injury; delafloxacin is not discussed).
• Moseley RH. Hepatotoxicity of antimicrobials and antifungal agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 463-82.

  (Review of hepatotoxicity of antibiotics; mentions that hepatocellular and cholestatic forms of injury have been reported due to the fluoroquinolones including cases of ductopenia, acute liver failure and death).
• MacDougall C. The quinolones. Sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. 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. 1015-8.

  (Textbook of pharmacology and therapeutics).
• Orman ES, Conjeevaram HS, Vuppalanchi R, Freston JW, Rochon J, Kleiner DE, Hayashi PH., DILIN Research Group. Clinical and histopathologic features of fluoroquinolone-induced liver injury. Clin Gastroenterol Hepatol. 2011;9:517–523.e3. [PMC free article: PMC3718017] [PubMed: 21356330]

  (Among 679 cases of drug induced liver injury presenting between 2004 and 2010 at 8 US medical centers, 12 [1.8%] were attributed to fluoroquinolones including 6 cipro-, 4 moxi-, 1 levo-, and 1 gatifloxacin; the average time to onset was 4 days [range 1-39], with both hepatocellular and cholestatic enzyme patterns, 7 with rash or fever, mortality was limited to those with hepatocellular injury and jaundice; hepatic injury was class specific; moxifloxacin cases included 3 men, 1 woman, ages 45-71 years, onset after 1-7 days, 1 with fever and 2 with rash [bilirubin 0.9-5.3 mg/dL, ALT 220-1311 U/L, Alk P 253-837 U/L], 1 patient developed vanishing bile duct syndrome and underwent liver transplantation: Case 1).
• Paterson JM, Mamdani MM, Manno M, Juurlink DN., Canadian Drug Safety and Effectiveness Research Network. Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study. CMAJ. 2012;184:1565–70. [PMC free article: PMC3470619] [PubMed: 22891208]

  (Population based, case control study of antibiotic exposure and subsequent hospitalization for liver injury within 30 days in elderly Canadian outpatients found weak associations with ciprofloxacin [adjusted odds ratio 1.56]), levofloxacin [2.06] and moxifloxacin [2.44], but not clarithromycin or cefuroxime).
• Hayashi PH, Chalasani NP. Liver injury in the elderly due to fluoroquinolones: should these drugs be avoided? CMAJ. 2012;184:1555–6. [PMC free article: PMC3470615] [PubMed: 22891207]

  (Editorial in response to Paterson [2012] stressing the low absolute risk of liver injury from the fluoroquinolones [4-9 per 100,000 exposures]).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, including 26 due to antibiotics, but none were attributed to fluoroquinolones).
• Alshammari TM, Larrat EP, Morrill HJ, Caffrey AR, Quilliam BJ, LaPlante KL. Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study. Am J Health Syst Pharm. 2014;71:37–43. [PubMed: 24352180]

  (Retrospective analysis of Veterans Affairs patients receiving a fluoroquinolone [n=7862] found a higher relative risk of developing acute liver injury after receipt of ciprofloxacin compared to matched controls [adjusted odds ratio: OR=1.29], but not after receipt of levofloxacin [OR=1.16) or moxifloxacin [OR=0.98]).
• 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, 38 cases [4%] were attributed to fluoroquinolones, including 16 due to ciprofloxacin [the 8th most common prescription drug cause], 13 due to levofloxacin and 8 to moxifloxacin).
• Bonkovsky HL, Kleiner DE, Gu J, Odin JA, Russo MW, Navarro VM, Fontana RJ, Ghabril MS, et al. U.S. Drug Induced Liver Injury Network Investigators. Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology. 2017;65:1267–77. [PMC free article: PMC5360519] [PubMed: 27981596]

  (Among 363 patients with drug induced liver injury who underwent liver biopsy, 26 [7%] had bile duct loss, of whom 94% developed evidence of chronic liver injury suggestive of vanishing bile duct syndrome, 2 of which were due to fluoroquinolones, 1 moxifloxacin and 1 levofloxacin).
• O'Riordan W, Mehra P, Manos P, Kingsley J, Lawrence L, Cammarata S. A randomized phase 2 study comparing two doses of delafloxacin with tigecycline in adults with complicated skin and skin-structure infections. Int J Infect Dis. 2015;30:67–73. [PubMed: 25448332]

  (Among 150 patients with complicated skin or skin structure infections treated with 1 of 2 doses of delafloxacin or tigercycline for 5-14 days, clinical efficacy and adverse event rates were similar; ALT elevations occurring in 3% of delafloxacin, but in none of tigecycline treated subjects).
• Pullman J, Gardovskis J, Farley B, Sun E, Quintas M, Lawrence L, Ling R, et al. PROCEED Study Group. Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections: A Phase 3, double-blind, randomized study. J Antimicrob Chemother. 2017;72:3471–80. [PMC free article: PMC5890686] [PubMed: 29029278]

  (Among 660 patients with acute bacterial skin or skin structure infections treated with delafloxacin or the combination of vancomycin and aztreonam, clinical response and adverse event rates were similar, ALT elevations above 5 times ULN occurred in 0.9% vs 1.5% of subjects, and no patient developed clinically apparent liver injury with jaundice).
• Markham A. Delafloxacin: first global approval. Drugs. 2017;77:1481–6. [PMC free article: PMC6208769] [PubMed: 28748399]

  (Review of the mechanism of action, pharmacology, clinical efficacy and safety of delafloxacin; mentions that aminotransferase elevations occur in 3-4% of treated patients, but cases of clinically apparent liver injury with jaundice were not observed in the prelicensure studies).
• Delafloxacin (Baxdela)--a new fluoroquinolone antibiotic. Med Lett Drugs Ther. 2018;60(1543):49–51. [PubMed: 29635263]

  (Concise review of the mechanism of action, clinical efficacy, safety and costs of delafloxacin shortly after its approval for use in the US; mentions adverse side effects of aminotransferase elevations [3%] and that it, like other fluoroquinolones, has a boxed warning about tendinitis, tendon rupture, peripheral neuropathy and CNS effects, and that it can also lead to C. difficile diarrhea).
• O'Riordan W, McManus A, Teras J, Poromanski I, Cruz-Saldariagga M, Quintas M, Lawrence L, et al. PROCEED Study Group. A comparison of the efficacy and safety of intravenous followed by oral delafloxacin with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections: a phase 3, multinational, double-blind, randomized study. Clin Infect Dis. 2018;67:657–66. [PMC free article: PMC6093995] [PubMed: 29518178]

  (Among 850 patients with acute bacterial skin or skin structure infections treated with delafloxacin or the combination of vancomycin and aztreonam for 5-14 days, clinical efficacy and overall adverse event rates were similar in the two groups, no patient developed clinically apparent liver injury with jaundice and ALT elevations above 5 times ULN occurred in 1.2% vs 1.9% of subjects).
• Comparison table: some systemic fluoroquinolones. Med Lett Drugs Ther. 2018;60:e57–e58. [PubMed: 29635268]

  (Table comparing 4 fluoroquinolones [cipro-, levo-, dela- and moxifloxacin] mentions that ALT and AST elevations are a class adverse event).
• Mavros MN, Theochari NA, Kyriakidou M, Economopoulos KP, Sava JA, Falagas ME. Fluoroquinolone-based versus β-lactam-based regimens for complicated intra-abdominal infections: a meta-analysis of randomised controlled trials. Int J Antimicrob Agents. 2019;53:746–54. [PubMed: 30639629]

  (Systematic review of controlled trials of fluoroquinolones versus β-lactam-based antibiotic regimens found similar rates of efficacy and adverse events; no discussion of ALT elevations or liver related toxicities).
• Kuula LSM, Viljemaa KM, Backman JT, Blom M. Fluoroquinolone-related adverse events resulting in health service use and costs: A systematic review. PLoS One. 2019;14:e0216029. [PMC free article: PMC6485715] [PubMed: 31026286]

  (Systematic review of observational studies on safety of fluoroquinolones concluded that due to lack of published literature, health service and costs could not be evaluated).