What are the potential issues with concurrent use of Insulin Glargine (insulin glargine) and Levofloxacin (levofloxacin, a fluoroquinolone antibiotic)?

From the Guidelines

There are no significant drug interactions between insulin glargine and levofloxacin, so these medications can generally be used together safely, as supported by the most recent guidelines 1. However, patients should monitor blood glucose levels more closely when starting levofloxacin, as fluoroquinolone antibiotics like levofloxacin can occasionally cause both hypoglycemia and hyperglycemia. Insulin glargine (Lantus, Basaglar, Toujeo) is a long-acting insulin that provides basal insulin coverage for approximately 24 hours, while levofloxacin is a broad-spectrum antibiotic typically dosed at 500-750mg once daily for 5-14 days depending on the infection being treated. Some key points to consider when using insulin glargine include:

• Starting doses can be estimated based on body weight (0.1–0.2 units/kg/day) and the degree of hyperglycemia, with individualized titration over days to weeks as needed 1.
• The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals 1.
• Control of fasting glucose can be achieved with human NPH insulin or a long-acting insulin analog, with long-acting basal analogs (U-100 glargine or detemir) demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia compared with NPH insulin 1. Patients should continue their prescribed insulin regimen while taking levofloxacin but should be aware of potential glucose fluctuations. The mechanism behind fluoroquinolone effects on glucose involves possible direct action on pancreatic beta cells affecting insulin secretion. Elderly patients, those with diabetes, kidney problems, or taking other medications that affect blood glucose are at higher risk for these effects and should be particularly vigilant about monitoring glucose levels during antibiotic treatment. It is also important to consider the cost of insulin, as it has been rising steadily over the past two decades, and human insulin (NPH and regular) may be a cost-effective alternative for some patients 1.

From the FDA Drug Label

7.3 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)].

Insulin Glargine and Levofloxacin Interaction:

• The FDA drug label recommends careful monitoring of blood glucose when levofloxacin is coadministered with antidiabetic agents, including insulin.
• Key Considerations: + Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported. + Careful monitoring of blood glucose is recommended. + No specific dosage adjustments are recommended for insulin glargine or levofloxacin when coadministered 2.
• Clinical Decision: Monitor blood glucose levels closely when administering levofloxacin with insulin glargine.

From the Research

Insulin Glargine and Levofloxacin Issues

• There are no direct studies on the interaction between insulin glargine and levofloxacin in the provided evidence.
• However, a study on moxifloxacin, a fluoroquinolone like levofloxacin, found that it had no clinically relevant effect on blood glucose homeostasis 3.
• The study also found that levofloxacin, when used as a comparator, was associated with two drug-related hypoglycaemic adverse events, both of mild severity 3.
• Insulin glargine has been studied in various contexts, including its use in critically ill patients 4 and noncritically ill surgical patients receiving parenteral nutrition 5.
• These studies found that insulin glargine was effective in reducing blood glucose levels and decreasing the incidence of hyperglycemic episodes, but may be associated with an increased risk of hypoglycemia 4, 5.
• Another study found that switching from continuous subcutaneous insulin infusion to multiple daily injections with insulin glargine and insulin lispro was safe and effective, with no significant increase in hypoglycemia 6.
• A review of higher concentration insulins, including insulin glargine 300 units/mL, highlighted the importance of considering bioequivalence, pen dose increments, and pen appearance when transitioning patients from lower concentration insulins 7.