Issue 153 Item 8 Repaglinide Potency Greatly Increased When Combined With Gemfib

If the combination is used, repaglinide dosage should be greatly reduced and blood glucose concentrations carefully monitored. Gemfibrozil raised the plasma concentration of repaglinide by 5.5-15.0 times and prolonged its half-life from 1.3 to 3.7 hours. A potentially hazardous interaction between gemfibrozil, a fibrate, and repaglinide, an oral hypoglycemic agent, has been found by Finnish specialists.

Gemfibrozil, especially in combination with itraconazole, greatly increased and prolonged the blood glucose-lowering effect of repaglinide, they found. Repaglinide thus became a long-acting and stronger anti-diabetic.

Clinicians should avoid using the two medications together, the specialists warned. If the combination is necessary, repaglinide dosage should be greatly reduced and blood glucose concentrations carefully monitored.

The specialists, clinical pharmacologists at Helsinki University Central Hospital, Finland, studied possible interactions of gemfibrozil, itraconazole and their combination with repaglinide in a randomised crossover study.

They enrolled 12 healthy volunteers who were given either gemfibrozil 600 mg., itraconazole 100 mg. (first dose 200 mg.), gemfibrozil and itraconazole together or placebo, all twice daily for 3 days. On the third day, the volunteers took a 0.25 mg. dose of repaglinide.

Plasma drug and blood glucose concentrations were followed for 7 hours and serum insulin and C-peptide concentrations for 3 hours post-dose.

Gemfibrozil raised the area under the plasma concentration-time curve of repaglinide by 5.5-15.0 times and prolonged its half-life from 1.3 to 3.7 hours.

Itraconazole alone raised repaglinide’s area under the plasma concentration-time curve by 1.1-1.9 times. But, the gemfibrozil-itraconazole combination raised it by 12.9-24.7 times and prolonged repaglinide’s half-life to 6.1 hours.

Gemfibrozil increased plasma repaglinide concentration at 7 hours by 28.6 times. The gemfibrozil-itraconazole combination increased plasma repaglinide concentration at 7 hours by 70.4 times. Diabetes Care 2003;26:

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