Fluctuating blood glucose levels in an elderly diabetic patient.

I read with great interest the letter by Bobba et al, (1) entitled "Hyperglycemia in an elderly diabetic patient: Drug-drug or drug-disease interaction?" in which an elderly patient experienced loss of glycemic control potentially due to the use of gatifloxacin, a newer fluoroquinolone antibacterial agent. The case report does emphasize the need for providers to consider potential drug-related causes or interactions when evaluating a patient with symptomatic alterations in glycemic control. A variety of pharmacologic agents have been linked to the development of abnormal glucose metabolism, diabetes mellitus, hypoglycemia and hyperglycemia. The case also highlights the need for providers to consider a number of patient-specific factors when dosing medications, such as age, body weight or body surface area, hepatic function, renal function, concomitant medications, and comorbid illness. The case report describes a recognized drug-drug interaction between a fluoroquinolone antibacterial agent and a sulfonylurea, associated with loss of glycemic control. In addition, one must consider the potential impact that an infectious process could have on the patient's serum glucose levels or if the patient experienced a rapid decrease in renal function which could lead to increased serum gatifloxacin levels. Potential complications due to disregarding appropriate dosing guidelines is a common theme in the medical literature regarding reports of older adults experiencing drug-related morbidities.

The interaction between fluoroquinolones and several antidiabetic agents, both sulfonylureas and nonsulfonylureas, leading to alterations in serum glucose levels, has been previously documented and is included in the product information for several fluoroquinolones. (2-8) Alterations associated with gatifloxacin have included both hypoglycemia and hyperglycemia. (9-13) With gatifloxacin in particular, hypoglycemic reactions have generally been identified during the first three days of gatifloxacin therapy. Hyperglycemic reactions were more common after the third day of therapy. (2) The patient described in this case report was at increased risk for this potential drug-associated reaction given his advanced age and diagnoses of diabetes mellitus and renal impairment. (9-10,12-13)

The initial dose of oral gatifloxacin remains 400 mg for most adults with renal impairment, but the dose should be decreased to at least 200 mg daily if creatinine clearance is less than 40 mL/min. (2) Of related importance, severe hypoglycemia associated with combinations of ciprofloxacin and glyburide has led to fatal events in some patients. (6-7) The sulfonylurea described in this case report, glipizide, is cleared more quickly than some related agents, such as glyburide, and glipizide also has inactive metabolites. (14) Glipizide has been used safely in diabetic patients with renal failure, and generally, glipizide doses do not have to be decreased for renal insufficiency. (15)

A variety of pharmacologic agents have been associated with alternations in glucose homeostasis. It is important for the provider to use caution in at-risk patients and consider the potential risks in using these medications in diabetic patients. Drugs linked with the development of hypoglycemia include aspirin and other salicylates, beta adrenergic blockers, and quinine. (16) Agents associated with the development or worsening of hyperglycemia include corticosteroids, estrogens, nonsteroidal antiinflammatory drugs, atypical antipsychotics, thiazide diuretics, protease inhibitors, diltiazem, phenytoin, lithium, niacin, and isoniazid. (16-17)

References

1. Bobba RK, Arsura EL. Hyperglycemia in an elderly diabetic patient: Drug-drug or drug-disease interaction? South Med J 2006;99:94-95.

2. Package insert. Tequin (gatifloxacin). Princeton. Bristol-Myers Squibb, revised May 2005.

3. Package insert. Avelox (moxifloxacin). West Haven, CT, Bayer, revised July 2005.

4. Package insert. Cipro (ciprofloxacin). West Haven, CT, Bayer, revised April 2005.

5. Package insert. Levaquin (levofloxacin). Raritan, NJ, Ortho-McNeil, revised August 2005.

6. Lin G, Hays DP, Spillane L. Refractory hypoglycemia from ciprofloxacin and glyburide interaction. J Toxicol Clin Toxicol 2004;42:295-297.

7. Roberge R, Kaplan R, Frank R, et al. Glyburide-ciprofloxacin interaction with resistant hypoglycemia. Ann Emerg Med 2000;36:160-163.

8. Menzies D, Dorsainvil P, Cunha B, et al. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002;113:232-234.

9. Blommel AL, and Lute RA. Severe hyperglycemia during renally adjusted gatifloxacin therapy. Annals Pharmacother 2005;39:1349-1352.

10. Happe MR, Mulhall BP, Maydonovitch BS, et al. Gatifloxacin-induced hyperglycemia. Ann Intern Med 2004;141:968-969.

11. Baker SE, Hangi MC. Possible gatifloxacin-induced hypoglycemia. Annals Pharmacother 2002;36:1722-1726.

12. Donaldson AR, Vandiver JR, and Fine CK. Possible gatifloxacin-induced hyperglycemia. Annals Pharmacother 2004;38:602-605.

13. Biggs WS. Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients. J Am Board Fam Pract 2003;16:455-457.

14. Ferner RE, Chaplin S. The relationship between the pharmacokinetics and pharmacodynamic effects of oral hypoglyeaemic drugs. Clin Pharmacokinet 1987;12:379-401.

15. Bennett WM, Aronoff GR, Golper TA, et al. Drug Prescribing in Renal Failure. Philadelphia, American College of Physicians. 1994.

16. Pandit MK, Burke J, Gustafson AB, et al. Drug-induced disorders of glucose tolerance. Ann Intern Med 1993;118:529-539.

17. Luna B, Feinglo MN. Drug-induced hyperglycemia. JAMA 2001;286:1945-1948.

Reamer L. Bushardt, PHARMD, PA-C

From the Department of Clinical Services, College of Health Professions, Medical University of South Carolina, Charleston, SC.

Reprint requests to Reamer L. Bushardt, PharmD, PA-C, Assistant Professor, Medical University of South Carolina, College of Health Professions, Department of Clinical Services, 151 Rutledge Avenue, Building B, PO Box 250962, Charleston, SC 29425. Email: [e-mail]

Accepted October 5, 2005.