Repaglinide

Indications

Repaglinide is used for: Type 2 DM

Adult Dose

Oral Type 2 diabetes mellitus Adult: Usual initial dose: 0.5 mg before main meals. Initial doses of 1 or 2 mg may be used in patients who have had previous hypoglycaemic treatment. May adjust dose at intervals of 1-2 wk, up to 4 mg before meals. Max dose: 16 mg daily. Hepatic impairment: May require longer intervals between dosage adjustments.

Child Dose

Safety and efficacy not established

Renal Dose

Renal Impairment CrCl 40-80 mL/minute: No adjustments necessary CrCl 20-40 mL/minute: 0.5 mg with meals; titrate slowly and monitor CrCl < 20 mL/minute: Data not available

Administration

Take 15 minutes before meal; no more than 4 meals/day

Contra Indications

Diabetic ketoacidosis; severe hepatic impairment, type 1 diabetes; hypersensitivity. Lactation.

Precautions

Myocardial infarction, coma, trauma during surgery, elderly, malnourished and debilitated patients. Hepatic or severe renal impairment. Pregnancy.

Pregnancy-Lactation

Pregnancy Limited available data from case reports and case series have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal, or fetal outcomes in women taking repaglinide while pregnant Clinical considerations Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity Animal studies Teratogenicity was not observed in rats and rabbits administered repaglinide during organogenesis at approximately 60 and 1 times the maximum daily clinical dose Offspring of rat dams exposed to repaglinide at ?22 times clinical exposure on a mg/m² basis during days 17 to 22 of gestation and during lactation were less viable and developed skeletal deformations consisting of shortening, thickening, and bending of the humerus during the postnatal period; this was not seen at doses up to 4 times clinical exposure Lactation No data on the presence of repaglinide in human milk, the effects on the breastfeeding infant, or the effects on milk production Because of the potential for hypoglycemia in breastfed infants, repaglinide is not recommended for use when breastfeeding Animal data Detected in breast milk of rat dams and lowered blood glucose levels were observed in the pups Cross fostering studies indicated that skeletal changes could be induced in control pups nursed by treated dams, although this occurred to a lesser degree than those pups treated in utero

Interactions

Cytochrome P450 3A4 inducers eg. rifampicin, barbiturates and carbamazepine may increase repaglinide metabolism. NSAIDs and other highly protein bound drugs eg, salicylates, sulphonamides, phenylbutazone, oral anticoagulants and hydantoins may potentiate action of repaglinide. Ketoconazole, fluconazole, itraconazole and erythromycin may increase plasma conc of repaglinide. Antagonistic effect with drugs causing hyperglycaemia. Concurrent use with gemfibrozil may lead to enhanced and prolonged blood glucose lowering effect. Potentially Fatal: Increased risk of myocardial infarction when used with isophane insulin.

Adverse Effects

Side effects of Repaglinide : Hypoglycaemia, nausea, diarrhoea, constipation, vomiting, dyspepsia, arthralgia, sinusitis, rhinitis, back pain; rash, pruritus, urticaria; visual disturbances.

Mechanism of Action

Repaglinide stimulates release of insulin from pancreatic beta-cells by inhibiting K efflux via closure of ATP regulated K channels. This results in depolarization of the cell and opening of voltage-dependent Ca channels, which increases influx of Ca into the beta cells and causes release of insulin.