Alogliptin and Norfloxacin: Interaction Details

a) The concurrent administration of ciprofloxacin with glyburide provoked persistent hypoglycemia in a 68-year-old man after a single dose of ciprofloxacin. The patient had previously been receiving a stable dose regimen of glyburide for treatment of noninsulin dependent diabetes mellitus, denying any prior episodes of hypoglycemia. At the time of admission, the man presented with confusion, diaphoresis and tremulousness, accompanied by a fasting blood glucose concentration of 20 mg/dL. Over the next 24 hours, his blood glucose concentrations oscillated between 25 mg/dL and 195 mg/dL despite ongoing treatment with 50% dextrose bolus injections followed by an intravenous infusion of 10% dextrose in 0.45% normal saline. Ciprofloxacin was replaced by a cephalosporin, and the patient's symptoms resolved after multiple bolus doses of 50% dextrose in conjunction with regular meals and a 10% dextrose infusion ².

b) Hypoglycemia and an elevated serum glyburide level after 1 week of ciprofloxacin use occurred in a patient receiving long-term glyburide therapy. An 89-year-old female suffered from confusion, slurred speech, and diaphoresis after receiving seven days of ciprofloxacin (250 mg twice a day) for acute cystitis. Her glucose level was 86 mg/dL after receiving intramuscular glucagon 2 mg. At the emergency department her glucose level was 57 mg/dL. The patient drank 8 oz. of orange juice fortified with two 1 oz. packets of sugar and ate a sandwich. Thirty minutes later her glucose level was 41 mg/dL. The patient was admitted with resistant hypoglycemia and required dextrose 10% intravenously and oral alimentation over the subsequent 24 hours to maintain euglycemia. Physicians prescribing antibiotics for patients receiving sulfonylurea therapy should consider the possibility of hypoglycemia if a fluoroquinolone is administered concurrently ³.

c) Severe and persistent hypoglycemia can occur in patients taking gatifloxacin and oral hypoglycemics concomitantly. A 74-year-old patient with a history of coronary artery disease and heart failure was admitted to the coronary care unit for a trial of milrinone therapy. The patient was taking repaglinide (0.5 mg every 8 hours) for type 2 diabetes mellitus. On hospital day 3, oral gatifloxacin 400 mg daily was prescribed for an uncomplicated urinary tract infection. The serum glucose level before gatifloxacin administration was 76 mg/dL. Repaglinide was discontinued 6 hours after the gatifloxacin dose because of his lack of appetite. Two hours after the second dose of gatifloxacin, when his glucose level was 27 mg/dL, he had a tonic-clonic seizure. Hypoglycemia continued for the next 32 hours. Gatifloxacin was discontinued and high-dose intravenous dextrose was administered and serum glucose levels normalized. Repaglinide therapy was resumed without subsequent hypoglycemia ⁴.

d) Severe and persistent hypoglycemia occurred in a 71-year-old woman taking gatifloxacin and oral hypoglycemics. A 71-year-old woman with type 2 diabetes mellitus was admitted to the hospital with a hip fracture. Her medication regimen consisted of glimepiride (2 mg before breakfast and 1 mg before dinner), with serum glucose levels in the 150 to 250 range. She was given intravenous gatifloxacin (400 mg daily) and clindamycin (900 mg every 8 hours) after developing an attack of acute cholecystitis. Glimepiride was held when gatifloxacin therapy was initiated. Her serum glucose levels ranged from 70 mg/dL to 150 mg/dL. She became diaphoretic and clammy with a serum glucose level of 22 mg/dL twelve hours after the first dose of gatifloxacin. She was administered a 50-g bolus of dextrose intravenously. A repeat serum glucose 4 hours later was 33 mg/dL; 8 hours later it was 41 mg/dL. Another 50-g bolus of dextrose and a dextrose intravenous drip (10% dextrose in water) was administered to the patient. Two hours later, her serum glucose level was 40 mg/dL. She received three intravenous bolus injections of 50 g of dextrose. Her serum glucose level was 37 mg/dL 4 hours later and 54 mg/dL 8 hours later. Gatifloxacin and glimepiride were discontinued the next day and her serum glucose levels returned to between 150 and 250 mg/dL. Glimepiride was restarted with no further hypoglycemia ⁴.

e) Severe and persistent hypoglycemia due to gatifloxacin occurred in an adult diabetes mellitus patient who was taking oral hypoglycemic agents. A 94-year-old female was admitted with shortness of breath following a right hip fracture. Her serum glucose level was 100 to 200 mg/dL. Her medications included glyburide (5 mg daily), pioglitazone (30 mg daily), furosemide, aspirin, pantoprazole, alpha-methyldopa, ramipril, clopidogrel, and verapamil. On hospital day 3, oral gatifloxacin (200 mg daily) was started as empiric therapy for a low-grade fever. Two hours after her daily morning dose of pioglitazone and glyburide, and 4 hours before the gatifloxacin, her serum glucose level was 217 mg/dL. Forty-five minutes after the first gatifloxacin dose, her serum glucose level was 42 mg/dL. She was given orange juice and oral glucose (8 g). Her serum glucose was 49 mg/dL 45 minutes later, and she was again given orange juice and glucose (8 g). She was then given dextrose 50 g intravenously. Three hours later her serum glucose was 31 mg/dL; six hours later it was 33 mg/dL; and nine hours later it was 33 mg/dL. Multiple doses of 50 g intravenous dextrose and an intravenous infusion of 50% dextrose in water was administered. Three hours later her serum glucose level was 58 mg/dL. Gatifloxacin, pioglitazone, and glyburide were not given on the next day, and her serum glucose level returned to between 100 and 200 mg/dL. Two days later pioglitazone and glyburide were restarted and serum glucose levels returned to between 100 and 200 mg/dL with no further episodes of hypoglycemia ⁴.

f) In patients with diabetes receiving glyburide 2.5 mg once daily, moxifloxacin 400 mg once daily for five days resulted in a decrease in the glyburide area under the concentration-time curve (AUC) and maximum concentration (Cmax) of 12% and 21%, respectively. However, blood glucose levels were slightly lower in patients receiving both glyburide and moxifloxacin as compared to patients receiving only glyburide, suggesting that this interaction is not clinically significant ⁵.

g) Symptomatic hypoglycemia occurred in a 73-year-old man after he received 2 days of concomitant therapy with gatifloxacin and glyburide. The patient had previously taken oral antidiabetic agents without difficulty for an unspecified number of years, along with warfarin, amiodarone, lisinopril, digoxin, amitriptyline, furosemide, and atorvastatin. Four days prior to admission, he began treatment for an exacerbation of COPD with oral gatifloxacin 400 milligrams (mg) daily taken concomitantly with his daily regimen of other medications, including glyburide 5 mg and twice-daily metformin 850 mg. The patient presented with complaints of night sweats, shaking episodes, lethargy, nausea and vomiting (contributing to recent poor oral nutritional intake), and dyspnea. Whole blood glucose measurement was 22 mg/deciliter. Gatifloxacin was discontinued after a total of 4 doses, and both glyburide and metformin had been discontinued one day prior to admission; however, restoration of euglycemia required 3 bolus infusions of dextrose 50% in addition to treatment with a 24-hour continuous infusion of dextrose 10%. The authors assign a Naranjo probability scale rating of 'possibly related' to the relationship between gatifloxacin and hypoglycemia ⁶.

h) A 68-year-old woman developed hypoglycemia within 24 hours of starting therapy with gatifloxacin 200 milligrams (mg) daily given concomitantly with her usual daily dose of glyburide 1.25 mg. Capillary blood glucose values did not exceed 70 to 80 mg/deciliter (dL) over 2 days despite treatment with intravenous glucose combined with discontinuation of glyburide. After discontinuing gatifloxacin, capillary blood glucose concentration exceeded 200 mg/dL, and stabilized within the range of 150 to 200 mg/dL after restarting therapy with glyburide ⁷.

i) An 82-year-old man developed hypoglycemia within 8 hours of starting therapy with gatifloxacin 400 milligrams (mg) daily given concomitantly with her usual daily dose of glipizide 5 mg. Capillary blood glucose values declined to 50 mg/deciliter (dL) over 8 hours, accompanied by signs of mental confusion, and the hypoglycemia persisted for 12 hours despite a continuous infusion of intravenous glucose 100 grams/liter. Serum glucose levels eventually returned to within normal range, yet declined again (nadir of 60 mg/dL) the next day after another dose of gatifloxacin and glipizide. After discontinuing gatifloxacin, capillary blood glucose remained stable on a reduced dose of glipizide ⁷.

j) Symptomatic hyperglycemia (serum glucose exceeding 500 mg/dL) occurred in an 82-year-old woman within 48 hours of adding gatifloxacin 200 mg daily to her usual regimen of glipizide 10 mg daily and metformin 1000 mg twice daily ⁷.

k) A 70-year-old woman experienced severe hypoglycemia shortly after coadministration of oral ciprofloxacin with her usual regimen of glibenclamide (glyburide). The patient's blood glucose levels had remained stable on glibenclamide 10 mg daily over the preceding 6-year period. Within approximately 12 hours of beginning a course of oral ciprofloxacin 250 mg twice daily, the woman experienced severe hypoglycemia (serum glucose concentration deemed undetectable) on 2 separate occasions. Serum glucose concentrations returned to reasonable levels after administration of intravenous glucose in conjunction with discontinuation of glibenclamide. The patient remained euglycemic over the course of ciprofloxacin therapy while glibenclamide was withheld, and then required resumption of her usual dose of glibenclamide after completing the ciprofloxacin regimen ⁸.