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- Avoid giving gatifloxacin to patients.
- Consider selecting an antibiotic other than a fluoroquinolone for an elderly patient with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, or renal insufficiency (A).
- Discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia, or if blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (C).
When was the last time you checked a glucose level before prescribing a fluoroquinolone? Though most side effects of these drugs are mild and self-limited (nausea, anorexia, vomiting, abdominal pain, diarrhea, taste disturbance, dizziness, headache, and somnolence), dysglycemia—hypoor hyperglycemia—is another side effect that is potentially fatal.
From their inception, fluoroquinolones were known to upset glucose metabolism. However, recent publication of several case reports of gatifloxacin-associated dysglycemia, and Bristol-Myers Squibb’s announcement of a contraindication for gatifloxacin in diabetic patients, brought the matter of potentially severe dysglycemia to the forefront. Strength of recommendation taxonomy (SORT): A patient-centered approach to grading evidence in the medical literature,” in the February 2004 Journal of Family Practice. A retrospective chart review of more than 17,000 hospitalized patients receiving levofloxacin, gatifloxacin, or ceftriaxone, showed 101 patients with glucose concentrations >200 mg/dL or <50 mg/dL within 72 hours of receiving the drugs. Of these 101 patients, 92 experienced hyperglycemia. Most of these patients had underlying renal insufficiency. Eighty-nine percent had diabetes mellitus and 40% were taking oral hypoglycemics. Hyperglycemia rates were greater with levofloxacin and gatifloxacin than with ceftriaxone; no difference was found between levofloxacin and gatifloxacin.6
Finally, a second retrospective chart review of a VA population identified 64,076 prescriptions written for fluoroquinolones between 1998 and 2003. More than 10,000 glucose values were measured during treatment or within 7 days of treatment completion. Hyperglycemia occurred much more often than hypoglycemia—in 11.6% of 32,000 patients. The majority (59%) of hyperglycemic episodes occurred in diabetic patients, and it was not clear that fluoroquinolone use caused the hyperglycemia. In contrast to the data listed above, gatifloxacin had a lower rate of associated hyperglycemia than either levofloxacin or ciprofloxacin.23
Studies finding no hyperglycemic effect. The studies reviewed in the section on hypoglycemia found no clinically significant hyperglycemic effect of fluoroquinolones.
Take-home points
As with hypoglycemia, most cases of fluoroquinolone-associated hyperglycemia have occurred in patients with NIDDM and mild-to-moderate renal insufficiency. More definitive risk factors for hyperglycemia include decreased insulin secretion (eg, IDDM), decreased insulin sensitivity (eg, NIDDM), advanced age, high carbohydrate intake, acute infection, stress, and corticosteroid use.24 While an association with fluoroquinolone use appears to be multifactorial and dependent on these underlying host factors, strong evidence is lacking.11 As opposed to the timing of hypoglycemic events, review of several case reports revealed that fluoroquinolone-associated hyperglycemia has generally occurred later in treatment, usually after 4 days of therapy, and with higher doses.
Summary of practice recommendations
The following conclusions and recommendations can be made based on the studies reviewed.
First, because the rate of fluoroquinolone-associated dysglycemia is highest with gatifloxacin, and most patients who experience fluoroquinolone-associated dysglycemia have diabetes, gatifloxacin should be avoided in patients who have diabetes (SOR: A).
Second, it’s wise to not use any fluoroquinolone in elderly patients with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, and/or renal insufficiency (SOR: A). If a fluoroquinolone must be used in these patients, favor levofloxacin or moxifloxacin over gatifloxacin (SOR: B).
Third, discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia and/or blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (SOR: C). If symptomatic hypo- or hyperglycemia does occur, administer appropriate therapy, and if necessary, admit the patient to the hospital for appropriate treatment (SOR: C).
Acknowledgments
The author would like to thanks Barry Weiss, MD, and M. Moe Bell, MD, for their assistance in editing this manuscript, and Robert Marlow, MD, for his assistance in evidence ratings.
CORRESPONDENCE
Martin Catero, MD Heuser Family Medicine Center, 7301 East Second Street, Suite 210, Scottsdale, AZ 85251. E-mail: [email protected]
1. Bristol-Myers Squibb Company. Tequin (gatifloxacin) package insert. Princeton, NJ; 2006.
2. Bayer Pharmaceuticals. Avelox (moxifloxacin) tablets/injection package insert. West Haven, CT: Bayer Pharmaceuticals; 2004.
3. Ortho-McNeil Pharmaceuticals. Levaquin (levofloxacin) tablets/injection package insert. Raritan, NJ: Ortho-McNeil; 2004.
4. Bayer Corporation. Cipro (ciprofloxacin) package insert. West Haven, CT; 2003.
5. Park-Wyllie LY, Juurlink DL, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006;354:1352-1361.Epub 2006 Mar 1.
6. Mohr JF, McKinnon PS, Peymann PJ, et al. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacother 2005;25:1303-1309.
7. Akpunow B, Michaelis J, Uy CN, et al. Multicenter postmarketing assessment of levofloxacin in the treatment of adults with community-acquired pneumonia. Clin Infect Dis 2004;38:S5-S15.
8. Letourneau G, Morrison H, McMorran M. Gatifloxacin (Tequin): hypoglycemia and hyperglycemia. Can Adverse React Newsletter 2003;13:1-2.
9. Frothingham R. Gatifloxacin associated with a 56-fold higher rate of glucose homeostasis abnormalities than comparator quinolones in the FDA spontaneous reporting database. Presented at the 44th interscience conference on antimicrobial agents and chemotherapy. Washington, DC, October 3-November 2, 2004.
10. Smith KM, Lomaestro BM. What role do fluoroquinolone antimicrobial agents play in cardiac dysfunction and altered glycemic control? J Pharm Pract 2003;16:349-360.
11. Donaldson AR, Vandiver JF, Finch CK. Possible gatifloxacin-induced hyperglycemia. Ann Pharmacother 2004;38:602-605.
12. Saraga A, Yokokura M, Gonoi T, et al. Effects of fluoroquinolones on insulin secretion and ß-cell ATP-sensitive K+ channels. Eur J Pharm 2004;497:111-117.
13. Leblanc M, Belanger C, Cossette P. Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy. Pharmacother 2004;24:926-931.
14. Menzies DJ, Dorsainvil PA, Cunha BA, et al. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002;113:232-234.
15. Lin G, Hays DP, Spillane L. Refractory hypoglycemia from ciprofloxacin and glyburide interaction. J Toxicol Clin Toxicol 2004;42:295-297.
16. Graumlich JF, Habis S, Avelino RR, et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case control study. Pharmacother 2005;25:1296-1302.
17. Gajjar DA, LaCreta FP, Kollia GD, et al. Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with non-insulin-dependent diabetes mellitus maintained with diet and exercise. Pharmacother 2000;20:76S-86S.
18. Gajjar DA, LaCreta FP, Uderman HD, et al. A dose-escalation study of the safety, tolerability, and pharmacokinetics of intravenous gatifloxacin in healthy adult men. Pharmacother 2000;20:49S-58S.
19. Gavin JR, Kubin R, Choudri S, et al. Moxifloxacin and glucose homeostasis. Drug Saf 2004;27:671-686.
20. Pichichero ME, Arguelas A, Dagan R. Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 2005;41:470-478.
21. Lawrence KR, Adra M, Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin. J Infect 2006;52:e177-180.Epub 2005 Nov 2.
22. Ambrose PG, Bhavnani SM, Cirincione BB, et al. Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction. J Antimicrob Chemother 2003;S2:434-440.
23. 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;61:2545-2548.
24. Gaglia JL, Wyckoff J, Abrahamson MJ. Acute hyperglycemic crisis in the elderly. Med Clin North Am 2004;88:1063-1084, xii.
- Avoid giving gatifloxacin to patients.
- Consider selecting an antibiotic other than a fluoroquinolone for an elderly patient with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, or renal insufficiency (A).
- Discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia, or if blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (C).
When was the last time you checked a glucose level before prescribing a fluoroquinolone? Though most side effects of these drugs are mild and self-limited (nausea, anorexia, vomiting, abdominal pain, diarrhea, taste disturbance, dizziness, headache, and somnolence), dysglycemia—hypoor hyperglycemia—is another side effect that is potentially fatal.
From their inception, fluoroquinolones were known to upset glucose metabolism. However, recent publication of several case reports of gatifloxacin-associated dysglycemia, and Bristol-Myers Squibb’s announcement of a contraindication for gatifloxacin in diabetic patients, brought the matter of potentially severe dysglycemia to the forefront. Strength of recommendation taxonomy (SORT): A patient-centered approach to grading evidence in the medical literature,” in the February 2004 Journal of Family Practice. A retrospective chart review of more than 17,000 hospitalized patients receiving levofloxacin, gatifloxacin, or ceftriaxone, showed 101 patients with glucose concentrations >200 mg/dL or <50 mg/dL within 72 hours of receiving the drugs. Of these 101 patients, 92 experienced hyperglycemia. Most of these patients had underlying renal insufficiency. Eighty-nine percent had diabetes mellitus and 40% were taking oral hypoglycemics. Hyperglycemia rates were greater with levofloxacin and gatifloxacin than with ceftriaxone; no difference was found between levofloxacin and gatifloxacin.6
Finally, a second retrospective chart review of a VA population identified 64,076 prescriptions written for fluoroquinolones between 1998 and 2003. More than 10,000 glucose values were measured during treatment or within 7 days of treatment completion. Hyperglycemia occurred much more often than hypoglycemia—in 11.6% of 32,000 patients. The majority (59%) of hyperglycemic episodes occurred in diabetic patients, and it was not clear that fluoroquinolone use caused the hyperglycemia. In contrast to the data listed above, gatifloxacin had a lower rate of associated hyperglycemia than either levofloxacin or ciprofloxacin.23
Studies finding no hyperglycemic effect. The studies reviewed in the section on hypoglycemia found no clinically significant hyperglycemic effect of fluoroquinolones.
Take-home points
As with hypoglycemia, most cases of fluoroquinolone-associated hyperglycemia have occurred in patients with NIDDM and mild-to-moderate renal insufficiency. More definitive risk factors for hyperglycemia include decreased insulin secretion (eg, IDDM), decreased insulin sensitivity (eg, NIDDM), advanced age, high carbohydrate intake, acute infection, stress, and corticosteroid use.24 While an association with fluoroquinolone use appears to be multifactorial and dependent on these underlying host factors, strong evidence is lacking.11 As opposed to the timing of hypoglycemic events, review of several case reports revealed that fluoroquinolone-associated hyperglycemia has generally occurred later in treatment, usually after 4 days of therapy, and with higher doses.
Summary of practice recommendations
The following conclusions and recommendations can be made based on the studies reviewed.
First, because the rate of fluoroquinolone-associated dysglycemia is highest with gatifloxacin, and most patients who experience fluoroquinolone-associated dysglycemia have diabetes, gatifloxacin should be avoided in patients who have diabetes (SOR: A).
Second, it’s wise to not use any fluoroquinolone in elderly patients with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, and/or renal insufficiency (SOR: A). If a fluoroquinolone must be used in these patients, favor levofloxacin or moxifloxacin over gatifloxacin (SOR: B).
Third, discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia and/or blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (SOR: C). If symptomatic hypo- or hyperglycemia does occur, administer appropriate therapy, and if necessary, admit the patient to the hospital for appropriate treatment (SOR: C).
Acknowledgments
The author would like to thanks Barry Weiss, MD, and M. Moe Bell, MD, for their assistance in editing this manuscript, and Robert Marlow, MD, for his assistance in evidence ratings.
CORRESPONDENCE
Martin Catero, MD Heuser Family Medicine Center, 7301 East Second Street, Suite 210, Scottsdale, AZ 85251. E-mail: [email protected]
- Avoid giving gatifloxacin to patients.
- Consider selecting an antibiotic other than a fluoroquinolone for an elderly patient with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, or renal insufficiency (A).
- Discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia, or if blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (C).
When was the last time you checked a glucose level before prescribing a fluoroquinolone? Though most side effects of these drugs are mild and self-limited (nausea, anorexia, vomiting, abdominal pain, diarrhea, taste disturbance, dizziness, headache, and somnolence), dysglycemia—hypoor hyperglycemia—is another side effect that is potentially fatal.
From their inception, fluoroquinolones were known to upset glucose metabolism. However, recent publication of several case reports of gatifloxacin-associated dysglycemia, and Bristol-Myers Squibb’s announcement of a contraindication for gatifloxacin in diabetic patients, brought the matter of potentially severe dysglycemia to the forefront. Strength of recommendation taxonomy (SORT): A patient-centered approach to grading evidence in the medical literature,” in the February 2004 Journal of Family Practice. A retrospective chart review of more than 17,000 hospitalized patients receiving levofloxacin, gatifloxacin, or ceftriaxone, showed 101 patients with glucose concentrations >200 mg/dL or <50 mg/dL within 72 hours of receiving the drugs. Of these 101 patients, 92 experienced hyperglycemia. Most of these patients had underlying renal insufficiency. Eighty-nine percent had diabetes mellitus and 40% were taking oral hypoglycemics. Hyperglycemia rates were greater with levofloxacin and gatifloxacin than with ceftriaxone; no difference was found between levofloxacin and gatifloxacin.6
Finally, a second retrospective chart review of a VA population identified 64,076 prescriptions written for fluoroquinolones between 1998 and 2003. More than 10,000 glucose values were measured during treatment or within 7 days of treatment completion. Hyperglycemia occurred much more often than hypoglycemia—in 11.6% of 32,000 patients. The majority (59%) of hyperglycemic episodes occurred in diabetic patients, and it was not clear that fluoroquinolone use caused the hyperglycemia. In contrast to the data listed above, gatifloxacin had a lower rate of associated hyperglycemia than either levofloxacin or ciprofloxacin.23
Studies finding no hyperglycemic effect. The studies reviewed in the section on hypoglycemia found no clinically significant hyperglycemic effect of fluoroquinolones.
Take-home points
As with hypoglycemia, most cases of fluoroquinolone-associated hyperglycemia have occurred in patients with NIDDM and mild-to-moderate renal insufficiency. More definitive risk factors for hyperglycemia include decreased insulin secretion (eg, IDDM), decreased insulin sensitivity (eg, NIDDM), advanced age, high carbohydrate intake, acute infection, stress, and corticosteroid use.24 While an association with fluoroquinolone use appears to be multifactorial and dependent on these underlying host factors, strong evidence is lacking.11 As opposed to the timing of hypoglycemic events, review of several case reports revealed that fluoroquinolone-associated hyperglycemia has generally occurred later in treatment, usually after 4 days of therapy, and with higher doses.
Summary of practice recommendations
The following conclusions and recommendations can be made based on the studies reviewed.
First, because the rate of fluoroquinolone-associated dysglycemia is highest with gatifloxacin, and most patients who experience fluoroquinolone-associated dysglycemia have diabetes, gatifloxacin should be avoided in patients who have diabetes (SOR: A).
Second, it’s wise to not use any fluoroquinolone in elderly patients with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, and/or renal insufficiency (SOR: A). If a fluoroquinolone must be used in these patients, favor levofloxacin or moxifloxacin over gatifloxacin (SOR: B).
Third, discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia and/or blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (SOR: C). If symptomatic hypo- or hyperglycemia does occur, administer appropriate therapy, and if necessary, admit the patient to the hospital for appropriate treatment (SOR: C).
Acknowledgments
The author would like to thanks Barry Weiss, MD, and M. Moe Bell, MD, for their assistance in editing this manuscript, and Robert Marlow, MD, for his assistance in evidence ratings.
CORRESPONDENCE
Martin Catero, MD Heuser Family Medicine Center, 7301 East Second Street, Suite 210, Scottsdale, AZ 85251. E-mail: [email protected]
1. Bristol-Myers Squibb Company. Tequin (gatifloxacin) package insert. Princeton, NJ; 2006.
2. Bayer Pharmaceuticals. Avelox (moxifloxacin) tablets/injection package insert. West Haven, CT: Bayer Pharmaceuticals; 2004.
3. Ortho-McNeil Pharmaceuticals. Levaquin (levofloxacin) tablets/injection package insert. Raritan, NJ: Ortho-McNeil; 2004.
4. Bayer Corporation. Cipro (ciprofloxacin) package insert. West Haven, CT; 2003.
5. Park-Wyllie LY, Juurlink DL, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006;354:1352-1361.Epub 2006 Mar 1.
6. Mohr JF, McKinnon PS, Peymann PJ, et al. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacother 2005;25:1303-1309.
7. Akpunow B, Michaelis J, Uy CN, et al. Multicenter postmarketing assessment of levofloxacin in the treatment of adults with community-acquired pneumonia. Clin Infect Dis 2004;38:S5-S15.
8. Letourneau G, Morrison H, McMorran M. Gatifloxacin (Tequin): hypoglycemia and hyperglycemia. Can Adverse React Newsletter 2003;13:1-2.
9. Frothingham R. Gatifloxacin associated with a 56-fold higher rate of glucose homeostasis abnormalities than comparator quinolones in the FDA spontaneous reporting database. Presented at the 44th interscience conference on antimicrobial agents and chemotherapy. Washington, DC, October 3-November 2, 2004.
10. Smith KM, Lomaestro BM. What role do fluoroquinolone antimicrobial agents play in cardiac dysfunction and altered glycemic control? J Pharm Pract 2003;16:349-360.
11. Donaldson AR, Vandiver JF, Finch CK. Possible gatifloxacin-induced hyperglycemia. Ann Pharmacother 2004;38:602-605.
12. Saraga A, Yokokura M, Gonoi T, et al. Effects of fluoroquinolones on insulin secretion and ß-cell ATP-sensitive K+ channels. Eur J Pharm 2004;497:111-117.
13. Leblanc M, Belanger C, Cossette P. Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy. Pharmacother 2004;24:926-931.
14. Menzies DJ, Dorsainvil PA, Cunha BA, et al. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002;113:232-234.
15. Lin G, Hays DP, Spillane L. Refractory hypoglycemia from ciprofloxacin and glyburide interaction. J Toxicol Clin Toxicol 2004;42:295-297.
16. Graumlich JF, Habis S, Avelino RR, et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case control study. Pharmacother 2005;25:1296-1302.
17. Gajjar DA, LaCreta FP, Kollia GD, et al. Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with non-insulin-dependent diabetes mellitus maintained with diet and exercise. Pharmacother 2000;20:76S-86S.
18. Gajjar DA, LaCreta FP, Uderman HD, et al. A dose-escalation study of the safety, tolerability, and pharmacokinetics of intravenous gatifloxacin in healthy adult men. Pharmacother 2000;20:49S-58S.
19. Gavin JR, Kubin R, Choudri S, et al. Moxifloxacin and glucose homeostasis. Drug Saf 2004;27:671-686.
20. Pichichero ME, Arguelas A, Dagan R. Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 2005;41:470-478.
21. Lawrence KR, Adra M, Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin. J Infect 2006;52:e177-180.Epub 2005 Nov 2.
22. Ambrose PG, Bhavnani SM, Cirincione BB, et al. Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction. J Antimicrob Chemother 2003;S2:434-440.
23. 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;61:2545-2548.
24. Gaglia JL, Wyckoff J, Abrahamson MJ. Acute hyperglycemic crisis in the elderly. Med Clin North Am 2004;88:1063-1084, xii.
1. Bristol-Myers Squibb Company. Tequin (gatifloxacin) package insert. Princeton, NJ; 2006.
2. Bayer Pharmaceuticals. Avelox (moxifloxacin) tablets/injection package insert. West Haven, CT: Bayer Pharmaceuticals; 2004.
3. Ortho-McNeil Pharmaceuticals. Levaquin (levofloxacin) tablets/injection package insert. Raritan, NJ: Ortho-McNeil; 2004.
4. Bayer Corporation. Cipro (ciprofloxacin) package insert. West Haven, CT; 2003.
5. Park-Wyllie LY, Juurlink DL, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006;354:1352-1361.Epub 2006 Mar 1.
6. Mohr JF, McKinnon PS, Peymann PJ, et al. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacother 2005;25:1303-1309.
7. Akpunow B, Michaelis J, Uy CN, et al. Multicenter postmarketing assessment of levofloxacin in the treatment of adults with community-acquired pneumonia. Clin Infect Dis 2004;38:S5-S15.
8. Letourneau G, Morrison H, McMorran M. Gatifloxacin (Tequin): hypoglycemia and hyperglycemia. Can Adverse React Newsletter 2003;13:1-2.
9. Frothingham R. Gatifloxacin associated with a 56-fold higher rate of glucose homeostasis abnormalities than comparator quinolones in the FDA spontaneous reporting database. Presented at the 44th interscience conference on antimicrobial agents and chemotherapy. Washington, DC, October 3-November 2, 2004.
10. Smith KM, Lomaestro BM. What role do fluoroquinolone antimicrobial agents play in cardiac dysfunction and altered glycemic control? J Pharm Pract 2003;16:349-360.
11. Donaldson AR, Vandiver JF, Finch CK. Possible gatifloxacin-induced hyperglycemia. Ann Pharmacother 2004;38:602-605.
12. Saraga A, Yokokura M, Gonoi T, et al. Effects of fluoroquinolones on insulin secretion and ß-cell ATP-sensitive K+ channels. Eur J Pharm 2004;497:111-117.
13. Leblanc M, Belanger C, Cossette P. Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy. Pharmacother 2004;24:926-931.
14. Menzies DJ, Dorsainvil PA, Cunha BA, et al. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002;113:232-234.
15. Lin G, Hays DP, Spillane L. Refractory hypoglycemia from ciprofloxacin and glyburide interaction. J Toxicol Clin Toxicol 2004;42:295-297.
16. Graumlich JF, Habis S, Avelino RR, et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case control study. Pharmacother 2005;25:1296-1302.
17. Gajjar DA, LaCreta FP, Kollia GD, et al. Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with non-insulin-dependent diabetes mellitus maintained with diet and exercise. Pharmacother 2000;20:76S-86S.
18. Gajjar DA, LaCreta FP, Uderman HD, et al. A dose-escalation study of the safety, tolerability, and pharmacokinetics of intravenous gatifloxacin in healthy adult men. Pharmacother 2000;20:49S-58S.
19. Gavin JR, Kubin R, Choudri S, et al. Moxifloxacin and glucose homeostasis. Drug Saf 2004;27:671-686.
20. Pichichero ME, Arguelas A, Dagan R. Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 2005;41:470-478.
21. Lawrence KR, Adra M, Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin. J Infect 2006;52:e177-180.Epub 2005 Nov 2.
22. Ambrose PG, Bhavnani SM, Cirincione BB, et al. Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction. J Antimicrob Chemother 2003;S2:434-440.
23. 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;61:2545-2548.
24. Gaglia JL, Wyckoff J, Abrahamson MJ. Acute hyperglycemic crisis in the elderly. Med Clin North Am 2004;88:1063-1084, xii.