Interactions between repaglinide and Adalat cc (NIFEdipine)
NIFEdipine and repaglinide (Moderate Drug-Drug)
MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of repaglinide, which is metabolized by the isoenzyme in the intestine and liver. In nine healthy volunteers, pretreatment with the CYP450 3A4 inhibitor clarithromycin (250 mg orally twice a day for 4 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of repaglinide (0.25 mg single oral dose) by 66% and 41%, respectively, compared to placebo. Increases in repaglinide Cmax and AUC values were observed in every subject. Clarithromycin also increased the mean elimination half-life of repaglinide by 21% (from 1.4 to 1.7 hours), as well as the mean incremental AUC from 0 to 3 hours of serum insulin by 51% and the maximum increase in the serum insulin concentration by 61%. No statistically significant differences were found in the blood glucose concentrations between the clarithromycin and placebo phases, and no subject developed symptomatic hypoglycemia as a result of the interaction. However, the lack of clinical adverse effects may be explained, at least partially, by frequent carbohydrate intake during the study and the use of a subtherapeutic dose of repaglinide.
MANAGEMENT: Because the antidiabetic effect of repaglinide is dose- and concentration-dependent, pharmacologic response to repaglinide should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to regularly monitor their blood sugar and counseled on how to recognize and treat hypoglycemia, which may include symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, and palpitations. The repaglinide dosage may require adjustment if an interaction is suspected.
