Cardiovascular and metabolic safety profiles of the fluoroquinolones

Expert Opinion on Drug Safety

Volumn 11, Issue 1, 2012, Pages 53-69

  Pugi, Alessandra ^a   Longo, Loreta ^a   Bartoloni, Alessandro ^a   Rossolini, Gian Maria ^b   Mugelli, Alessandro ^a   Vannacci, Alfredo ^a   Lapi, Francesco ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b UNIVERSITY OF SIENA   (Italy)

Author keywords

Adverse event; Dysglycemia; Fluoroquinolones; Heart; Safety

Indexed keywords

AMIODARONE; AZITHROMYCIN; CIPROFLOXACIN; DIGOXIN; GATIFLOXACIN; GLIBENCLAMIDE; GLICLAZIDE; INSULIN; LEVOFLOXACIN; MOXIFLOXACIN; PLACEBO; PROCAINAMIDE; PRULIFLOXACIN; SOTALOL;

CARDIOVASCULAR DISEASE; DATA EXTRACTION; DIABETES MELLITUS; DISORDERS OF CARBOHYDRATE METABOLISM; DRUG MEGADOSE; DRUG SAFETY; ELECTROLYTE DISTURBANCE; GLUCOSE METABOLISM DISORDER; HEART ATRIUM FIBRILLATION; HUMAN; HYPERTENSION; HYPOGLYCEMIA; MEDICAL RECORD REVIEW; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESPIRATORY TRACT INFECTION; REVIEW; SYSTEMATIC REVIEW; URINARY TRACT INFECTION;

ANTI-BACTERIAL AGENTS; BLOOD GLUCOSE; CARDIOVASCULAR DISEASES; DIABETES MELLITUS; FLUOROQUINOLONES; HEART DISEASES; HUMANS; RISK FACTORS;

EID: 84555190239     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2011.624512     Document Type: Review

References (100)

1. Pfaller MA, Jones RN, Marshall SA, et al. Inducible amp C beta-lactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE). Diagn Microbiol Infect Dis 1997;28(4):211-19 (Pubitemid 27425219)
2. Neu HC. The crisis in antibiotic resistance. Science 1992;257(5073):1064- 73
3. Urbanek K, Kolar M, Strojil J, et al. Utilization of fluoroquinolones and Escherichia coli resistance in urinary tract infection: inpatients and outpatients. Pharmacoepidemiol Drug Saf 2005;14(10):741-5 (Pubitemid 41489455)
4. Elseviers MM, Ferech M, Vander Stichele RH, et al. Antibiotic use in ambulatory care in Europe (ESAC data 1997-2002): trends, regional differences and seasonal fluctuations. Pharmacoepidemiol Drug Saf 2007;16(1):115-23 (Pubitemid 46164984)
5. Vander Stichele RH, Elseviers MM, Ferech M, et al. European surveillance of antimicrobial consumption (ESAC): data collection performance and methodological approach. Br J Clin Pharmacol 2004;58(4):419-28 (Pubitemid 39312466)
6. OsMed. OsMed-L'uso dei Farmaci in Italia-Rapporto Nazionale; 2008
7. OsMed. OsMed-L'uso dei Farmaci in Italia-Rapporto Nazionale; 2009
8. Mehlhorn AJ, Brown DA. Safety concerns with fluoroquinolones. Ann Pharmacother 2007;41(11):1859-66 (Pubitemid 350044349)
9. Mohr JF, McKinnon PS, Peymann PJ, et al. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacotherapy 2005;25(10):1303-9 (Pubitemid 41407626)
10. Owens RC Jr, Ambrose PG. Clinical use of the fluoroquinolones. Med Clin North Am 2000;84(6):1447-69
11. Owens RC Jr, Bhavnani SM, Ambrose PG. Assessment of pharmacokinetic- pharmacodynamic target attainment of gemifloxacin against Streptococcus pneumoniae. Diagn Microbiol Infect Dis 2005;51(1):45-9 (Pubitemid 40040567)
12. Yew WW. Management of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis: current status and future prospects. Kekkaku 2011;86(1):9-16
13. WHO. Treatment of tuberculosis: guidelines. 4th edition. 2009
14. Goossens H, Ferech M, Vander Stichele R, et al. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005;365(9459):579-87 (Pubitemid 40247914)
15. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 2005;41(Suppl 2):S144-57 (Pubitemid 40962485)
16. Liu HH. Safety profile of the fluoroquinolones: focus on levofloxacin. Drug Saf 2010;33(5):353-69
17. Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 2001;21(12):1468-72 (Pubitemid 33117251)
18. Frothingham R. Glucose homeostasis abnormalities associated with use of gatifloxacin. Clin Infect Dis 2005;41(9):1269-76 (Pubitemid 41534661)
19. Haerian H, McHugh P, Brown R, et al. Gatifloxacin produces both hypoglycemia and hyperglycemia: a retrospective study. Am J Med Sci 2008;335(2):95-8 (Pubitemid 351253403)
20. Lapi F, Tuccori M, Motola D, et al. Safety profile of the fluoroquinolones: analysis of adverse drug reactions in relation to prescription data using four regional pharmacovigilance databases in Italy. Drug Saf 2010;33(9):789-99
21. Leone R, Venegoni M, Motola D, et al. Adverse drug reactions related to the use of fluoroquinolone antimicrobials: an analysis of spontaneous reports and fluoroquinolone consumption data from three Italian regions. Drug Saf 2003;26(2):109-20 (Pubitemid 36188561)
22. Zambon A, Polo Friz H, Contiero P, et al. Effect of macrolide and fluoroquinolone antibacterials on the risk of ventricular arrhythmia and cardiac arrest: an observational study in Italy using case-control, case-crossover and case-time-control designs. Drug Saf 2009;32(2):159-67
23. Rosignoli MT, Di Loreto G, Dionisio P. Effects of prulifloxacin on cardiac repolarization in healthy subjects: a randomized, crossover, double-blind versus placebo, moxifloxacin-controlled study. Clin Drug Investig 2010;30(1):5-14
24. Keam SJ, Perry CM. Prulifloxacin. Drugs 2004;64(19):2221-34; discussion 35-6
25. Aspinall SL, Good CB, Jiang R, et al. Severe dysglycemia with the fluoroquinolones: a class effect? Clin Infect Dis 2009;49(3):402-8
26. Lode H. Safety and tolerability of commonly prescribed oral antibiotics for the treatment of respiratory tract infections. Am J Med 2010;123(4 Suppl):S26-38
27. EMEA/CHMP/PhVWP/810358. Pharmacovigilance Working Party (PhVWP) 2010(1012)
28. Lewis RJ, Mohr JF III. Dysglycaemias and fluoroquinolones. Drug Saf 2008;31(4):283-92 (Pubitemid 351441577)
29. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000;356(9237):1255-9
30. Aronson JK, Hauben M. Anecdotes that provide definitive evidence. BMJ 2006;333(7581):1267-9 (Pubitemid 46032359)
31. Atasoy H, Erdem G, Ceyhan M, et al. Hypertension associated with ciprofloxacin use in an infant. Ann Pharmacother 1995;29(10):1049
32. Samaha FF. QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin. Am J Med 1999;107(5):528-9 (Pubitemid 29528348)
33. Iannini PB, Doddamani S, Byazrova E, et al. Risk of torsades de pointes with non-cardiac drugs. Prolongation of QT interval is probably a class effect of fluoroquinolones. BMJ 2001;322(7277):46-7 (Pubitemid 32066266)
34. Siepmann M, Kirch W. Drug points: tachycardia associated with moxifloxacin. BMJ 2001;322(7277):23 (Pubitemid 32066252)
35. Paltoo B, O'Donoghue S, Mousavi MS. Levofloxacin induced polymorphic ventricular tachycardia with normal QT interval. Pacing Clin Electrophysiol 2001;24(5):895-7 (Pubitemid 32437032)
36. Gandhi PJ, Menezes PA, Vu HT, et al. Fluconazole-and levofloxacin-induced torsades de pointes in an intensive care unit patient. Am J Health Syst Pharm 2003;60(23):2479-83 (Pubitemid 44712868)
37. Amankwa K, Krishnan SC, Tisdale JE. Torsades de pointes associated with fluoroquinolones: importance of concomitant risk factors. Clin Pharmacol Ther 2004;75(3):242-7 (Pubitemid 38314874)
38. Prabhakar M, Krahn AD. Ciprofloxacin-induced acquired long QT syndrome. Heart Rhythm 2004;1(5):624-6 (Pubitemid 39462725)
39. Daya SK, Gowda RM, Khan IA. Ciprofloxacin-and hypocalcemia-induced torsade de pointes triggered by hemodialysis. Am J Ther 2004;11(1):77-9
40. Flyer JL. Identifying patients at risk for QT interval prolongation: case studies. J Fam Pract 2005(Suppl):S18-19 (Pubitemid 40807671)
41. Nykamp DL, Blackmon CL, Schmidt PE, et al. QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother 2005;39(3):543-6 (Pubitemid 40270923)
42. Flanagan MC, Mitchell ES, Haigney MC. Ciprofloxacin-induced torsade de pointes. Int J Cardiol 2006;113(2):239-41 (Pubitemid 44755000)
43. Letsas KP, Sideris A, Kounas SP, et al. Drug-induced QT interval prolongation after ciprofloxacin administration in a patient receiving olanzapine. Int J Cardiol 2006;109(2):273-4 (Pubitemid 44399739)
44. Altin T, Ozcan O, Turhan S, et al. Torsade de pointes associated with moxifloxacin: a rare but potentially fatal adverse event. Can J Cardiol 2007;23(11):907-8 (Pubitemid 350011275)
45. Kazmierczak J, Peregud-Pogorzelska M, Rzeuski R. QT Interval prolongation and torsades de pointes due to a coadministration of ciprofloxacin and azimilide in a patient with implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 2007;30(8):1043-6 (Pubitemid 47196324)
46. Knorr JP, Moshfeghi M, Sokoloski MC. Ciprofloxacin-induced Q-T interval prolongation. Am J Health Syst Pharm 2008;65(6):547-51 (Pubitemid 351429716)
47. Nair MK, Patel K, Starer PJ. Ciprofloxacin-induced torsades de pointes in a methadone-dependent patient. Addiction 2008;103(12):2062-4
48. Keivanidou A, Arnaoutoglou C, Krommydas A, et al. Ciprofloxacin induced acquired long QT syndrome in a patient under class III antiarrhythmic therapy. Cardiol J 2009;16(2):172-4
49. Zeineh NS. A toxic combination. Am J Med 2010;123(8):707-8
50. Patel PD, Afshar H, Birnbaum Y. Levofloxacin-induced torsades de pointes. Tex Heart Inst J 2010;37(2):216-17
51. Salinas Arce J, Romero R, Solorzano P. A case of prolonged QT interval and torsades de pointes due to ciprofloxacin. Rev Esp Cardiol 2010;63(1):111-12
52. Ibrahim M, Omar B. Ciprofloxacin-induced torsade de pointes. Am J Emerg Med 2010. Epub ahead of print
53. Roberge RJ, Kaplan R, Frank R, et al. Glyburide-ciprofloxacin interaction with resistant hypoglycemia. Ann Emerg Med 2000;36(2):160-3 (Pubitemid 30667024)
54. Bharani A, Kumar H. Drug points: diabetes inspidus induced by ofloxacin. BMJ 2001;323(7312):547 (Pubitemid 32835575)
55. Lin G, Hays DP, Spillane L. Refractory hypoglycemia from ciprofloxacin and glyburide interaction. J Toxicol Clin Toxicol 2004;42(3):295-7 (Pubitemid 39166757)
56. Friedrich LV, Dougherty R. Fatal hypoglycemia associated with levofloxacin. Pharmacotherapy 2004;24(12):1807-12 (Pubitemid 39578967)
57. Lawrence KR, Adra M, Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin. J Infect 2006;52(6):e177-80 (Pubitemid 43811973)
58. Wang S, Rizvi AA. Levofloxacin-induced hypoglycemia in a nondiabetic patient. Am J Med Sci 2006;331(6):334-5
59. Kanbay M, Aydogan T, Bozalan R, et al. A rare but serious side effect of Levofloxacin: hypoglycemia in a geriatric patient. Diabetes Care 2006;29(7):1716-17 (Pubitemid 44127619)
60. Singh M, Jacob JJ, Kapoor R, et al. Fatal hypoglycemia with levofloxacin use in an elderly patient in the post-operative period. Langenbecks Arch Surg 2008;393(2):235-8
61. Vallurupalli S, Huesmann G, Gregory J, et al. Levofloxacin-associated hypoglycaemia complicated by pontine myelinolysis and quadriplegia. Diabet Med 2008;25(7):856-9
62. Gibert AE, Porta FS. Hypoglycemia and levofloxacin: a case report. Clin Infect Dis 2008;46(7):1126-7 (Pubitemid 351589886)
63. Kelesidis T, Canseco E. Levofloxacin-induced hypoglycemia: a rare but life-threatening side effect of a widely used antibiotic. Am J Med 2009;122(3):e3-4
64. Garber SM, Pound MW, Miller SM. Hypoglycemia associated with the use of levofloxacin. Am J Health Syst Pharm 2009;66(11):1014-19
65. Kelesidis T, Canseco E. Quinolone-induced hypoglycemia: a life-threatening but potentially reversible side effect. Am J Med 2010;123(2):e5-6
66. Yamaguchi H, Kawai H, Matsumoto T, et al. Post-marketing surveillance of the safety of levofloxacin in Japan. Chemotherapy 2007;53(2):85-103 (Pubitemid 46377215)
67. Poluzzi E, Raschi E, Motola D, et al. Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA Adverse Event Reporting System. Drug Saf 2010;33(4):303-14
68. Clark DW, Layton D, Wilton LV, et al. Profiles of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolone antibacterials: experience from large cohorts from the Drug Safety Research Unit Prescription-Event Monitoring database. Drug Saf 2001;24(15):1143-54 (Pubitemid 34151347)
69. Corrao G, Botteri E, Bagnardi V, et al. Generating signals of drug-adverse effects from prescription databases and application to the risk of arrhythmia associated with antibacterials. Pharmacoepidemiol Drug Saf 2005;14(1):31-40 (Pubitemid 40089576)
70. Corrao G, Botteri E, Bertu L, et al. Exploring the effect of transient exposure on the risk of acute events by means of time-window designs: an application to fluoroquinolone antibacterials and arrhythmia. Pharmacoepidemiol Drug Saf 2006;15(1):31-7 (Pubitemid 43174183)
71. Makaryus AN, Byrns K, Makaryus MN, et al. Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event? South Med J 2006;99(1):52-6
72. Meropol SB, Chan KA, Chen Z, et al. Adverse events associated with prolonged antibiotic use. Pharmacoepidemiol Drug Saf 2008;17(5):523-32 (Pubitemid 351722040)
73. Coblio NA, Mowrey K, McCright P, et al. Use of a data warehouse to examine the effect of fluoroquinolones on glucose metabolism. Am J Health Syst Pharm 2004;61(23):2545-8 (Pubitemid 40403565)
74. Graumlich JF, Habis S, Avelino RR, et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study. Pharmacotherapy 2005;25(10):1296-302 (Pubitemid 41407625)
75. Park-Wyllie LY, Juurlink DN, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006;354(13):1352-61
76. Lodise T, Graves J, Miller C, et al. Effects of gatifloxacin and levofloxacin on rates of hypoglycemia and hyperglycemia among elderly hospitalized patients. Pharmacotherapy 2007;27(11):1498-505 (Pubitemid 350060205)
77. LaPlante KL, Mersfelder TL, Ward KE, et al. Prevalence of and risk factors for dysglycemia in patients receiving gatifloxacin and levofloxacin in an outpatient setting. Pharmacotherapy 2008;28(1):82-9
78. Basyigit I, Kahraman G, Ilgazli A, et al. The effects of levofloxacin on ECG parameters and late potentials. Am J Ther 2005;12(5):407-10 (Pubitemid 41445137)
79. Demolis JL, Kubitza D, Tenneze L, et al. Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects. Clin Pharmacol Ther 2000;68(6):658-66 (Pubitemid 32059992)
80. Gajjar DA, LaCreta FP, Kollia GD, et al. Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with noninsulin-dependent diabetes mellitus maintained with diet and exercise. Pharmacotherapy 2000;20(6 Pt 2):76S-86S (Pubitemid 30390619)
81. Noel GJ, Natarajan J, Chien S, et al. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003;73(4):292-303 (Pubitemid 36403589)
82. Noel GJ, Goodman DB, Chien S, et al. Measuring the effects of supratherapeutic doses of levofloxacin on healthy volunteers using four methods of QT correction and periodic and continuous ECG recordings. J Clin Pharmacol 2004;44(5):464-73 (Pubitemid 38509714)
83. Morganroth J, Dimarco JP, Anzueto A, et al. A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. Chest 2005;128(5):3398-406 (Pubitemid 41698670)
84. Tsikouris JP, Peeters MJ, Cox CD, et al. Effects of three fluoroquinolones on QT analysis after standard treatment courses. Ann Noninvasive Electrocardiol 2006;11(1):52-6
85. Taubel J, Naseem A, Harada T, et al. Levofloxacin can be used effectively as a positive control in thorough QT/QTc studies in healthy volunteers. Br J Clin Pharmacol 2010;69(4):391-400
86. Sanguinetti MC, Jiang C, Curran ME, et al. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995;81(2):299-307
87. Malik M, Hnatkova K, Schmidt A, et al. Electrocardiographic QTc changes due to moxifloxacin infusion. J Clin Pharmacol 2009;49(6):674-83
88. Glass SK, Pearl DL, McEwen SA, et al. A province-level risk factor analysis of fluoroquinolone consumption patterns in Canada (2000-06). J Antimicrob Chemother 2010;65(9):2019-27
89. Ferech M, Coenen S, Malhotra-Kumar S, et al. European Surveillance of Antimicrobial Consumption (ESAC): outpatient quinolone use in Europe. J Antimicrob Chemother 2006;58(2):423-7 (Pubitemid 44294958)
90. Bouchrif B, Paglietti B, Murgia M, et al. Prevalence and antibiotic-resistance of Salmonella isolated from food in Morocco. J Infect Dev Ctries 2009;3(1):35-40
91. Meng CY, Smith BL, Bodhidatta L, et al. Etiology of diarrhea in young children and patterns of antibiotic resistance in Cambodia. Pediatr Infect Dis J 2011;30(4):331-5
92. Yanagi D, De Vries GC, Rahardjo D, et al. Emergence of fluoroquinolone-resistant strains of Salmonella enterica in Surabaya, Indonesia. Diagn Microbiol Infect Dis 2009;64(4):422-6
93. Lacroix P, Crumb WJ, Durando L, et al. Prulifloxacin: in vitro (HERG current) and in vivo (conscious dog) assessment of cardiac risk. Eur J Pharmacol 2003;477(1):69-72 (Pubitemid 38366087)
94. Gallelli L, Gallelli A, Vero G, et al. Acute renal failure probably induced by prulifloxacin in an elderly woman: a first case report. Clin Drug Investig 2006;26(1):49-53 (Pubitemid 43098409)
95. Stahlmann R, Lode H. Safety considerations of fluoroquinolones in the elderly: an update. Drugs Aging 2010;27(3):193-209
96. Maeda N, Tamagawa T, Niki I, et al. Increase in insulin release from rat pancreatic islets by quinolone antibiotics. Br J Pharmacol 1996;117(2):372-6 (Pubitemid 26030294)
97. Ge TF, Law PY, Wong HY, et al. Gatifloxacin affects GLUT1 gene expression and disturbs glucose homeostasis in vitro. Eur J Pharmacol 2007;573(1-3):70-4 (Pubitemid 47464227)
98. McGowan KM, Long SD, Pekala PH. Glucose transporter gene expression: regulation of transcription and mRNA stability. Pharmacol Ther 1995;66(3):465-505
99. Zimmerli W. Clinical practice. Vertebral osteomyelitis. N Engl J Med 2010;362(11):1022-9
100. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004;351(16):1645-54