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Journal of Toxicology
CLINICAL TOXICOLOGY
Vol. 42, No. 3, pp. 295297, 2004
CASE REPORT
Refractory Hypoglycemia from Ciprofloxacin and Glyburide
Interaction
George Lin, M.D., Daniel P. Hays, Pharm.D.,
and Linda Spillane, M.D.*
Department of Emergency Medicine, University of Rochester,
Rochester, New York, USA
ABSTRACT
Patients taking multiple medications may suffer from
unpredictable and complex
drugdrug interactions resulting in significant morbidity and
mortality. There are few
reports in the literature of hypoglycemia with concurrent
administration of an oral
hyperglycemic agent and a fluoroquinolone antibiotic. We present
a case of a diabetic
patient taking glyburide who was prescribed ciprofloxacin and
developed prolonged
hypoglycemia, which persisted for over 24 hours. The mechanisms
by which these
agents interact to produce prolonged hypoglycemia are complex
and probably
multifactorial. Patients stabilized on glyburide who are started
on a fluoroquinolone
should have their glucose levels monitored closely.
Key Words: Refractory hypoglycemia; Ciprofloxacin; Glyburide;
Glyburide
interaction; Ciprofloxacin interaction.
INTRODUCTION
Patients with multiple medical problems taking
multiple medications are at increased risk of drug
drug interactions as new medications are added to their
drug regimen (1,2). These interactions are complex and
may be difficult to predict despite an understanding
of drug metabolism and mechanisms of action. There
are few reports in the literature of hypoglycemia
with concurrent administration of an oral hyperglyce-
mic agent and a fluoroquinolone antibiotic (35). We
present a case of a diabetic patient taking glyburide
who was prescribed ciprofloxacin and developed
prolonged hypoglycemia.
CASE PRESENTATION
A 68-year-old man with a history of coronary
artery disease, atrial fibrillation, and Type II diabetes
*Correspondence: Linda Spillane, M.D., Department of Emergency
Medicine, University of Rochester, Box 655, 601 Elmwood
Ave., Rochester, NY 14642, USA; E-mail:
[email protected].
295
DOI: 10.1081/CLT-120037431 0731-3810 (Print); 1097-9875
(Online)
Copyright D 2004 by Marcel Dekker, Inc. www.dekker.com
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mellitus presented to the emergency department (ED)
with sudden onset of confusion, tremors, diaphoresis,
and weakness. The day prior to admission he was
started on ciprofloxacin 250 mg twice a day for an
uncomplicated urinary tract infection. His wife report-
ed that the afternoon of admission the patient was
confused, diaphoretic, and tremulous. His mental
statusprogressively declined until he became unresponsive.
Upon EMS arrival, his finger stick blood glucose
(FSBG) was 20 mg/dl. The patient was given one
ampoule (50 mL) of 50% dextrose (D50) with some
improvement in his mental status.
The patients past medical history was significant
for noninsulin-dependent diabetes mellitus, coronary
artery disease, atrial fibrillation, hypertension, and
renal insufficiency (serum creatinine 2.3 mg/dl).
Current medications included twice daily glyburide
1.25 mg and furosemide 40 mg and once daily warfarin
3 mg, fosinopril 10 mg, clopidogrel 75 mg, lovastatin
40 mg and metoprolol XL 50 mg. He had receivedonly one dose of
ciprofloxacin 250 mg. The patient
later denied any past episodes of hypoglycemia or
recent changes in medications except for the addition
of ciprofloxacin. At baseline the patient was coherent,
ambulatory, and fully functional.
On ED arrival, the patient was alert and oriented to
time, person, and place. The initial vital signs were
temperature 35.1C, respiratory rate 18/min, heart rate
54 beats/min, and blood pressure 124/78 mmHg. His
physical examination was normal except for tremu-
lousness, diaphoresis, and an irregular heart rhythm.
The patient was given a second ampoule of D50
and started on 10% dextrose in half normal saline (D101/2 NS) at
100 cc/hr. His mental status improved and a
small meal was provided. Laboratory test results includeda white
cell count (WBC) 11,600 per mm
3, (84.3%
neutrophils) and a hematocrit of 29%. Serum electrolyte
values were sodium 138 mmol/l, potassium 4.4 mmol/l,
chloride 98 mmol/l, carbon dioxide 32 mmol/l; serum
urea nitrogen 24 mg/dl, creatinine 1.8 mg/dl, glucose
24 mg/dl (FSBG 28 mg/dl), and INR 3.5. These initial
blood glucose levels were drawn prior to the patient
receiving D50 or being started on a D10 NS infusion.
Serum troponin was not elevated. Urinalysis showed
specific gravity of 1.010, 2+ leukocyte esterase, 3+
hemoglobin, 69 RBC/HPF, and 60 WBC/HPF. Urine
culture grew Pseudomonas and Klebsiella species. There
was no occult blood in his stool.The ciprofloxacin was replaced
by a cephalosporin
based on urine culture susceptibility. The patient
displayed refractory hypoglycemia (Table 1) that
persisted over 24 h, resolving after multiple doses of
D50, regular meals, and a D10 1/2 NS infusion. His
lethargy and mental status waxed and waned in relation
to his blood glucose, and he returned to baseline with
resolution of his hypoglycemia.
Table 1. Chronological blood glucose levels.
Time Blood glucose mg/dl Food and juice Intravenous dextrose
17:50 20 Juice and meal 25 g D50 given by EMS
19:00 28 (BG) 24 (Serum) 25 g D50; D10 NS at 100 cc./hr.
started
20:50 109
23:30 50 25 g D50
00:45 37 50 g D50
03:30 52 50 g D50
06:30 50 25 g D50
09:00 45
09:15 25 25 g D50
09:35 158 Breakfast
11:30 50 Juice and meal 25 g D50
12:30 195 IV changed to D5 NS
13:35 145 Sandwich
15:00 57 Meal
16:00 65
17:00 53 25 g D50
19:00 91
21:20 71
23:30 165
*Over the next 24 h glucose levels were checked every 4 h and
ranged from 140 to 206 mg/dl.
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DISCUSSION
We report a case of prolonged hypoglycemia
apparently due to an interaction between the broad-
spectrum fluoroquinolone (ciprofloxacin) and a second-
generation sulfonylurea hypoglycemic agent (glyburide).
Because glyburide has a long duration of action
(24 h) and its active metabolites are renally excreted,
one could postulate that worsening renal insufficiency
might have caused prolonged hypoglycemia. Howev-
er, our patient was not clinically dehydrated, had a
stable creatinine (compared to previously recorded
laboratory values), and had been on his current
medications for at least 6 months. Our hypothesis
that the hypoglycemia was caused by a drugdrug
interaction is supported by a case reported in the
literature in which the authors measured elevated
levels of serum glyburide in a patient also taking
ciprofloxacin (5).
The cellular mechanisms by which glyburide and
ciprofloxacin interact to produce hypoglycemia are
poorly described but likely to be complex and
multifactorial. Mechanisms might include interactions
at one or more of the P450 isoenzymes (58) or
ciprofloxacin-related blockage of ATP-potassium chan-
nels that are responsible for insulin control (10).
In the report by Roberge et al, the patient
developed hypoglycemia after treatment with cipro-
floxacin for 1 week (5). Our patient developed sig-
nificant hypoglycemia after one dose. Although we
cannot prove with certainty that the hypoglycemia wascaused by
the addition of ciprofloxacin, a search for
other possible etiologies was not successful. The
patient did not have an infection or worsening renal
failure and was not started on other new medications.
CONCLUSIONS
The concurrent administration of ciprofloxacin and
glyburide can result in prolonged hypoglycemia.
Patients stabilized on glyburide who are started on a
fluoroquinolone should have their glucose levels
monitored closely.
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Submitted July 24, 2003
Accepted January 28, 2004
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Interaction 297
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