Repaglinide dosing

Repaglinide doses are usually taken within 15 minutes of the meal, but time may vary from immediately preceding the meal to as long as 30 minutes before the meal. Starting dose For patients not previously treated or whose glycosylated hemoglobin (HbA-ic) is less than 8%, the starting dose is 0.5 mg with each meal. For patients... 

Dose range Dose range is 0.5 to 4 mg taken with meals. Repaglinide may be dosed preprandially 2, 3, or 4 times daily in response to changes in the patient s meal pattern. Maximum recommended daily dose is 16 mg. 

Patient management Monitor long-term efficacy by measurement of HbA- c levels approximately every 3 months. When hypoglycemia occurs in patients taking a combination of repaglinide and a thiazolidinedione or repaglinide and metformin, reduce the dose of repaglinide. 

The starting dose and dose adjustments for combination therapy are the same as repaglinide monotherapy. Carefully adjust the dose of each drug to determine the minimal dose required. 

Renal function impairment Patients with type 2 diabetes who have severe renal function impairment should initiate repaglinide with the 0.5 mg dose subsequently, carefully titrate patients. 

Hepatic function impairment Patients with impaired liver function may be exposed to higher concentrations of repaglinide and its metabolites. Use repaglinide cautiously in patients with impaired liver function. Utilize longer intervals between dose adjustments to allow full assessment of response. 

Uses Hypertriglyceridemia, coronary heart Dz Action Fibric acid Dose 1200 mg/d PO bid 30 min ac am pm Caution [C, ] t Warfarin effect, sulfony-lureas t risk of myopathy w/ HMG-CoA reductase inhibitors X effects w/ cyclosporine Contra Renal/hepatic impair (SCr >2.0 mg/dL), gallbladder Dz, primary biliary cirrhosis, use w/ repaglinide (i glucose) Disp Tabs 600 mg SE Cholelithiasis, GI upset Interactions t Effects OF anticoagulants, sulfonylureas t risk of rhabdomyolysis W/ HMG-CoA reductase inhibitors X effects W/ rifampin X effects OF cyclosporine EMS t Effects of anticoagulants OD May... 

In a multicenter, double-blind, randomized, fixed-dose trial of placebo and repaglinide 1 mg and 4 mg for 24 weeks in 361 patients there were no episodes of severe hypoglycemia (28). Most patients withdrew from the placebo group because of hyperglycemia, hypoglycemia, erythematous rash, headache, diarrhea, fatigue, or abnormal vision. Adverse effects had about the same frequencies in the two groups. 

In renal impairment the half-life of repaglinide is prolonged. Patients with severe renal impairment (creatinine clearance 20-40 ml/minute) had excess accumulation of the drug after taking multiple doses for 5 days (55). 

However, in a formal study bezafibrate and fenofibrate did not affect the pharmacokinetics or pharmacodynamics of a single dose of repaglinide 0.25 mg (63). 

Studies involving rifampicin and repaglinide have yielded conflicting results, perhaps because of timing and dosages. In one study rifampicin had no effect on the pharmacokinetics and pharmacodynamics of a single dose repaglinide... 

In a more recent study, 12 male volunteers took rifampicin 600 mg/day for 7 days followed by two doses of repaglinide 4 mg 24 hours apart the AUC for repaglinide was reduced by 50% on day 7, and by 80% on day 8 (67). Timing of the drugs may alter the clinical effects. 

CYP2C8 and CYP3A4 are involved in the metabolism of repaglinide (68). Trimethoprim is a selective inhibitor of CYP2C8. When nine healthy volunteers aged 19-23 years, 8 men) took placebo or trimethoprim 160 mg bd for 3 days followed by 0.25 mg of repaglinide 1 hour after the last dose of trimethoprim, the AUC of repaglinide increased by 61% and the Cmax increased by 41% compared with placebo. 

Moses RG, Gomis R, Frandsen KB, Schlienger JL, Dedov I. Flexible meal-related dosing with repaglinide facilitates gly-cemic control in therapy-naive type 2 diabetes. Diabetes Care 2001 24(l) ll-5. 

Jovanovic L, Dailey G 3rd, Huang WC, Strange P, Goldstein BJ. Repaglinide in type 2 diabetes a 24-week, fixed-dose efficacy and safety study. J Clin Pharmacol 2000 40(l) 49-57. 

Schumacher S, Abbasi I, Weise D, Hatorp V, Sattler K, Sieber J, Hasslacher C. Single- and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment. Eur J Clin Pharmacol 2001 57(2) 147-52. 

POTASSIUM-SPARING DIURETICS REPAGUNIDE 1 hypoglycaemic effect Antagonistic effect Higher doses of repaglinide needed... 

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