Trade Names:Prandin- Tablets 0.5 mg- Tablets 1 mg- Tablets 2 mgGlucoNorm (Canada)
Decreases blood glucose by stimulating insulin release from the pancreas.
Rapidly and completely absorbed from GI tract. T max is 1 h (single and multiple doses). Absolute bioavailability is 56%. Mean C max is decreased 20%; AUC is decreased 12.4% by food.
Vd is 31 L (IV). Protein binding and binding to human albumin is greater than 98%.
Completely metabolized by oxidative biotransformation and direct conjugation with glucuronic acid. CYP-450 enzymes, mainly CYP3A4, are involved in Nî“¸dealkylation to oxidized dicarboxylic acid (M2), then to the aromatic amine (M1), and acyl glucuronide (M7) (inactive metabolites).
Eliminated in feces (90% recovered) and urine (8%). Total body Cl is 38 L/h (IV). The t ½ is about 1 h.
AUC and C max increased in severe renal function impairment.Hepatic Function Impairment
Higher and more prolonged serum concentrations in patients with moderate to severe hepatic function impairment.
Adjunct to diet and exercise to lower blood glucose in patients with nonî“¸insulinî“¸dependent diabetes mellitus (type 2) whose hyperglycemia cannot be controlled by diet and exercise alone. Can be used with metformin or thiazolidinediones (eg, rosiglitazone) when hyperglycemia cannot be controlled by exercise, diet, and monotherapy with metformin, sulfonylureas, repaglinide, or thiazolidinediones.
Insulinî“¸dependent (type 1) diabetes; diabetic ketoacidosis with or without coma; hypersensitivity to repaglinide or its ingredients.
No fixed dosage regimen; periodically monitor blood glucose to determine minimum effective dose. Double preprandial dose up to 4 mg with each meal until satisfactory response is achieved (max dose, 16 mg/day). Allow 1 wk to elapse after each dose adjustment to assess response.Patients Not Previously Treated or Whose HbA 1c is Less Than 8%Adults
PO Initial dose is 0.5 mg with each meal.Patients Previously Treated or Whose HbA 1c is More Than or Equal to 8%Adults
PO Initial dose 1 to 2 mg with each meal.Combination therapyAdults
PO The starting dose and dosage adjustments for combination therapy are the same as repaglinide monotherapy.
Store tablets at controlled room temperature (below 77°F). Keep tightly closed and protect from moisture.
May increase repaglinide metabolism.Drugs that inhibit CYP3A4 (eg, erythromycin, ketoconazole, miconazole)
May inhibit repaglinide metabolism.Drug that produce hyperglycemia (eg, calcium channel blockers, corticosteroids, diuretics, estrogens and oral contraceptives, isoniazid, nicotinic acid, phenothiazines, phenytoin, sympathomimetics, thyroid products)
May lead to loss of glycemic control. Monitor patient and adjust therapy when these agents are started or stopped.Gemfibrozil
May result in enhanced and prolonged blood glucoseî“¸lowering effects of repaglinide. Patients receiving repaglinide should not start gemfibrozil; patients receiving gemfibrozil should not start taking repaglinide.Gemfibrozil plus itraconazole
Itraconazole and gemfibrozil have a synergistic inhibitory effect on repaglinide metabolism. Patients taking gemfibrozil and repaglinide should not receive itraconazole.Levonorgestrel and ethinyl estradiol
Plasma levels of these agents and those of repaglinide may be elevated.Protein bound drugs (eg, betaî“¸adrenergic blocking agents, MAOIs, NSAIDs, probenecid, salicylates, sulfonamides)
May potentiate hypoglycemic effect of repaglinide.Simvastatin
Repaglinide plasma levels may be increased.
None well documented.
Serious CV reactions (4%); cardiac ischemic reactions (2%); deaths caused by CV reactions (0.5%).
Alopecia, Stevensî“¸Johnson syndrome (postmarketing).
Diarrhea, nausea (5%); dyspepsia (4%); constipation, vomiting (3%); tooth disorder (2%); pancreatitis (postmarketing).
Thrombocytopenia, leukopenia (less than 1%); hemolytic anemia, severe hepatic dysfunction (postmarketing).
Arthralgia, back pain (6%).
Upper respiratory tract infection (16%); sinusitis, bronchitis (6%).
Chest pain, paresthesia (3%); allergy (2%).
Monitor blood glucose to determine minimum effective dose, detect primary failure, and to detect secondary failure. Monitor glycosylated hemoglobin levels (A 1c ) to determine patient's longerî“¸term response to therapy.
Category C . Insulin is recommended to be used during pregnancy to maintain blood glucose levels as close to normal as possible.
Safety and efficacy not established.
Elderly may be more susceptible to the hypoglycemic action of repaglinide. Hypoglycemia may be difficult to recognize in the elderly.
Initiate therapy with 0.5 mg dose in patients with severe renal function impairment and use caution when titrating dose.
Use with caution. Allow longer intervals between dosage adjustments.
Proper patient selection, dosage, and instructions to patients are important to avoid hypoglycemic episodes. Elderly, debilitated, or malnourished patients, and patients with adrenal, pituitary, hepatic, or severe renal function impairment may be particularly susceptible to the hypoglycemic action of glucoseî“¸lowering drugs.
Patients stabilized on any diabetic regimen may experience loss of glycemic control when exposed to stress, including trauma, fever, infection, or surgery. At such times, it may be necessary to discontinue repaglinide and administer insulin.
Coma, hypoglycemia, impairment, neurologic, seizure.
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