Inrebic and Repaglinide Tablets

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer information for this interaction is not currently available.MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of repaglinide, which is partially metabolized by the isoenzyme. In nine healthy volunteers, administration of a single 0.25 mg dose of repaglinide following pretreatment with the potent CYP450 3A4 inhibitor clarithromycin (250 mg orally twice a day for 4 days) resulted in a 66% increase in mean repaglinide peak plasma concentration (Cmax) and a 41% increase in systemic exposure (AUC) compared to administration after placebo. Clarithromycin also increased the mean elimination half-life of repaglinide from 1.4 to 1.7 hours, as well as the mean incremental AUC (0 to 3 hours) of serum insulin by 51% and the maximum increase in serum insulin by 61%. Similarly, in 12 healthy volunteers, pretreatment with itraconazole (200 mg orally followed by 100 mg twice daily for 3 days) increased the AUC of a single 0.25 mg dose of repaglinide by 40% compared to administration after placebo. In eight healthy male volunteers, the mean Cmax and AUC of a single 2 mg dose of repaglinide increased by 7% and 15%, respectively, following pretreatment with ketoconazole 200 mg/day for 5 days. No significant differences in blood glucose levels or adverse events were observed in these studies between repaglinide alone and in combination with the CYP450 3A4 inhibitor. However, clinical significance of the interaction in diabetics cannot be precluded due to potentially reduced counter-regulatory response to hypoglycemia in these patients. CYP450 3A4 inhibitors can also enhance the pharmacokinetic interaction between repaglinide and CYP450 2C8 and/or OATP 1B1 inhibitors such as gemfibrozil. In 12 healthy volunteers, gemfibrozil (600 mg orally twice a day for 3 days) alone increased the AUC of a single 0.25 mg dose of repaglinide by 8.1-fold compared to placebo and prolonged its half-life from 1.3 to 3.7 hours, while gemfibrozil plus itraconazole (200 mg orally followed by 100 mg twice daily for 3 days) increased the AUC of repaglinide by 19.4-fold and prolonged its half-life to 6.1 hours. Plasma repaglinide concentration at 7 hours was increased 28.6-fold by gemfibrozil and 70.4-fold by gemfibrozil plus itraconazole. Rare cases of severe hypoglycemia have been reported in patients taking this combination during postmarketing surveillance. 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. References Khamaisi M, Leitersdorf E "Severe hypoglycemia from clarithromycin-repaglinide drug interaction." Pharmacotherapy 28 (2008): 682-4 "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc, Princeton, NJ. Niemi M, Backman JT, Neuvonen M, Neuvonen PJ "Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide." Diabetologia 46 (2003): 347-51 Niemi M, Neuvonen PJ, Kivisto KT "The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide." Clin Pharmacol Ther 70 (2001): 58-65 Hatorp V, Hansen KT, Thomsen MS "Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide." J Clin Pharmacol 43 (2003): 649-60 Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT "CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide." Br J Clin Pharmacol 56 (2003): 305-14 Tornio A, Niemi M, Neuvonen M, et al. "The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose: evidence for mechanism-based inhibition of CYP2C8 in vivo." Clin Pharmacol Ther 84 (2008): 403-11 View all 7 references

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of repaglinide, which is partially metabolized by the isoenzyme. In nine healthy volunteers, administration of a single 0.25 mg dose of repaglinide following pretreatment with the potent CYP450 3A4 inhibitor clarithromycin (250 mg orally twice a day for 4 days) resulted in a 66% increase in mean repaglinide peak plasma concentration (Cmax) and a 41% increase in systemic exposure (AUC) compared to administration after placebo. Clarithromycin also increased the mean elimination half-life of repaglinide from 1.4 to 1.7 hours, as well as the mean incremental AUC (0 to 3 hours) of serum insulin by 51% and the maximum increase in serum insulin by 61%. Similarly, in 12 healthy volunteers, pretreatment with itraconazole (200 mg orally followed by 100 mg twice daily for 3 days) increased the AUC of a single 0.25 mg dose of repaglinide by 40% compared to administration after placebo. In eight healthy male volunteers, the mean Cmax and AUC of a single 2 mg dose of repaglinide increased by 7% and 15%, respectively, following pretreatment with ketoconazole 200 mg/day for 5 days. No significant differences in blood glucose levels or adverse events were observed in these studies between repaglinide alone and in combination with the CYP450 3A4 inhibitor. However, clinical significance of the interaction in diabetics cannot be precluded due to potentially reduced counter-regulatory response to hypoglycemia in these patients. CYP450 3A4 inhibitors can also enhance the pharmacokinetic interaction between repaglinide and CYP450 2C8 and/or OATP 1B1 inhibitors such as gemfibrozil. In 12 healthy volunteers, gemfibrozil (600 mg orally twice a day for 3 days) alone increased the AUC of a single 0.25 mg dose of repaglinide by 8.1-fold compared to placebo and prolonged its half-life from 1.3 to 3.7 hours, while gemfibrozil plus itraconazole (200 mg orally followed by 100 mg twice daily for 3 days) increased the AUC of repaglinide by 19.4-fold and prolonged its half-life to 6.1 hours. Plasma repaglinide concentration at 7 hours was increased 28.6-fold by gemfibrozil and 70.4-fold by gemfibrozil plus itraconazole. Rare cases of severe hypoglycemia have been reported in patients taking this combination during postmarketing surveillance.

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.

Inrebic

Generic Name: fedratinib

Brand name: Inrebic

Synonyms: n.a.

What is Inrebic?

Repaglinide Tablets

Generic Name: repaglinide

Brand name: Prandin

Synonyms: Repaglinide

What is Repaglinide Tablets?