What are the potential issues with concomitant use of Glipizide (Glipizide) and Levofloxacin (Levofloxacin)?

From the Guidelines

Glipizide and levofloxacin should not be taken together due to potential drug interactions that can cause dangerous hypoglycemia (low blood sugar). If you are taking glipizide for diabetes and need an antibiotic, ask your healthcare provider about alternative antibiotics to levofloxacin. Fluoroquinolone antibiotics like levofloxacin can enhance the blood sugar-lowering effects of sulfonylureas like glipizide, potentially causing severe hypoglycemia that may require medical attention 1.

Key Considerations

• The interaction between glipizide and levofloxacin can lead to severe hypoglycemia, which may require medical attention.
• If no alternative antibiotic is available and you must take both medications, your doctor should reduce your glipizide dose temporarily and you should monitor your blood glucose levels more frequently (at least 3-4 times daily) 1.
• Watch for hypoglycemia symptoms including shakiness, dizziness, sweating, confusion, and weakness.
• If you experience these symptoms, immediately consume 15 grams of fast-acting carbohydrates (like juice or glucose tablets) and recheck your blood sugar after 15 minutes.

Alternative Antibiotics

• According to the surviving sepsis campaign guidelines, alternative antibiotics such as vancomycin, aminoglycosides, or beta-lactams may be considered in place of levofloxacin 1.
• The choice of alternative antibiotic should be based on the specific infection being treated and the patient's individual needs.

Monitoring and Management

• Close monitoring of blood glucose levels is essential when taking glipizide and levofloxacin together.
• Patients should be educated on the symptoms of hypoglycemia and how to manage them.
• Healthcare providers should be aware of the potential interaction between glipizide and levofloxacin and take steps to mitigate the risk of hypoglycemia.

From the FDA Drug Label

1. 3 Antidiabetic Agents Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are coadministered [see Warnings and Precautions (5.11); Adverse Reactions (6.2), Patient Counseling Information (17.4)].
2. 11 Blood Glucose Disturbances As with other fluoroquinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with levofloxacin, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs in a patient being treated with levofloxacin, levofloxacin should be discontinued and appropriate therapy should be initiated immediately [see Adverse Reactions (6.2); Drug Interactions (7.3); Patient Counseling Information (17.4)].

Key Issues with Glipizide and Levofloxacin:

• Blood Glucose Disturbances: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, can occur when levofloxacin is coadministered with antidiabetic agents like glipizide.
• Monitoring: Careful monitoring of blood glucose is recommended when these agents are coadministered.
• Hypoglycemic Reaction: If a hypoglycemic reaction occurs, levofloxacin should be discontinued and appropriate therapy should be initiated immediately. 2 2

From the Research

Glipizide and Levofloxacin Issues

• The use of levofloxacin in patients with type 2 diabetes who are receiving glipizide has been associated with an increased risk of hypoglycemia 3, 4.
• A case report described a 58-year-old man with type 2 diabetes who developed hypoglycemia after receiving levofloxacin in conjunction with glipizide 3.
• Another study found that levofloxacin was associated with a statistically significant increased risk of severe hypoglycemia in users of glipizide, with an odds ratio of 2.09 (95% CI: 1.35-3.25) 4.
• The mechanism of this interaction is not fully understood, but it is thought to be related to the pharmacokinetic and pharmacodynamic properties of levofloxacin and glipizide 5.
• Patients with type 2 diabetes who are receiving glipizide and are prescribed levofloxacin should be closely monitored for signs of hypoglycemia, and their blood glucose levels should be regularly checked 5, 3.
• The use of alternative antibiotics that are not associated with an increased risk of hypoglycemia may be considered in patients with type 2 diabetes who are receiving glipizide 6, 4.

Comparison with Other Medications

• A study compared the efficacy and safety of dapagliflozin with glipizide in patients with type 2 diabetes who had inadequate glycemic control with metformin, and found that dapagliflozin produced less hypoglycemia than glipizide 7.
• The study also found that dapagliflozin was associated with significant weight loss and improved glycemic control compared to glipizide 7.
• However, the use of dapagliflozin was also associated with an increased risk of genital and urinary tract infections, which responded to standard treatment and rarely led to study discontinuation 7.

Antibiotics and Hypoglycemia Risk

• A study found that several antibiotics, including levofloxacin, were associated with an increased risk of hypoglycemia in patients with type 2 diabetes who were receiving sulfonylureas or meglitinides 6.
• The study found that cefditoren, tigecycline, ertapenem, and clarithromycin were associated with hypoglycemia even when not taken with sulfonylureas or meglitinides 6.
• The use of antibiotics in patients with type 2 diabetes should be carefully considered, and patients should be closely monitored for signs of hypoglycemia 6, 4.