Repaglinide
Indications
Repaglinide is used for:
Type 2 DM
Adult Dose
Oral
Type 2 diabetes mellitus
Adult: Usual initial dose: 0.5 mg. 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
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.