Trade Names:PrandiMet- Tablets repaglinide 1 mg/metformin 500 mg- Tablets repaglinide 2 mg/metformin 500 mg
Adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes who are already treated with a meglitinide (eg, repaglinide) and metformin or who have inadequate glycemic control on a meglitinide alone or metformin alone.
Renal function impairment (eg, serum creatinine levels of 1.5 mg/dL or higher in men, 1.4 mg/dL or higher in women, or abnormal CrCl); acute or chronic metabolic acidosis, including diabetic ketoacidosis; coadministration of both gemfibrozil and itraconazole; known hypersensitivity to any component of the product.
Starting dose is based on the patient's current regimen, drug effectiveness, and tolerability.Patients Inadequately Controlled With Metformin MonotherapyAdults
PO Start with repaglinide 1 mg/metformin 500 mg twice daily with meals and gradually increase the dose (based on glycemic control) to reduce the risk of hypoglycemia with repaglinide.Patients Inadequately Controlled With Meglitinide MonotherapyAdults
PO Start with 500 mg of the metformin component of repaglinide/metformin twice daily and gradually increase the dose (based on glycemic control) to reduce the GI adverse reactions associated with metformin.Patients Currently Taking Repaglinide and Metformin ConcomitantlyAdults
PO Start with the doses of repaglinide and metformin similar to, but not exceeding, the current doses, then titrate to the maximum daily dose necessary to achieve glycemic control.
Do not store above 77°F. Protect from moisture.
The effect of metformin on lactate metabolism may be potentiated.Cationic drugs (eg, amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin)
May increase metformin serum concentrations by competing for tubular secretion.CYP2C8 inducers (eg, rifampin), CYP3A4 inducers (eg, rifampin)
Repaglinide serum concentrations may be reduced, decreasing the efficacy.CYP2C8 inhibitors (eg, gemfibrozil, trimethoprim), CYP3A4 inhibitors (eg, clarithromycin, cyclosporine, grapefruit juice, itraconazole, ketoconazole, telithromycin)
Repaglinide serum concentrations may be elevated, increasing the pharmacologic effect and adverse reactions. Repaglinide is contraindicated in patients taking both gemfibrozil and itraconazole.Drugs that cause hyperglycemia (eg, corticosteroids, diazoxide, diuretics, phenothiazines, phenytoin)
May increase blood glucose, interfering with glycemic control.Drugs that cause hypoglycemia (eg, aspirin)
May decrease blood glucose, interfering with glycemic control.Insulin
Repaglinide is not indicated for use in combination with isophane (NPH) insulin.Parenteral iodinated contrast material
Because of the increased risk of metformin-induced lactic acidosis, discontinue repaglinide/metformin at the time of or prior to the procedure, and withhold repaglinide/metformin for 48 h subsequent to the procedure and reinstate treatment only after renal function has been evaluated and found to be healthy.
None well documented.
Except for postmarketing reactions, which were reported with repaglinide, the following adverse reactions were reported with combined use of repaglinide plus metformin.
Alopecia, Stevens-Johnson syndrome (postmarketing).
Diarrhea (19%); nausea (15%); pancreatitis (postmarketing).
Hemolytic anemia, severe hepatic function impairment including hepatitis and jaundice (postmarketing).
Respiratory tract infection (11%).
Lactic acidosis: Although rare, lactic acidosis can occur and be fatal in approximately 50% of cases, as a result of metformin accumulation (eg, renal function impairment), or with pathophysiologic conditions associated with tissue hypoperfusion and hypoxia. The risk of lactic acidosis increases with the degree of renal function impairment and the patient's age.
Monitor blood glucose to determine therapeutic response. Monitor vitamin B 12 levels at 2- to 3-year intervals in patients at risk of deficiency. Initial and periodic monitoring of hematologic parameters, including hemoglobin, hematocrit, and RBC, and monitoring of renal function should be done annually.
Category C .
Safety and efficacy not established.
Because aging is associated with reduced renal function, use with caution, titrating to establish the minimum dose for adequate glycemic control.
Risk of metformin accumulation and lactic acidosis increases with the degree of renal function impairment.
Hepatic function impairment has been associated with cases of lactic acidosis.
Promptly evaluate patients who develop laboratory abnormalities for clinical illness for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose, and, if indicated, blood pH, lactate, pyruvate, and metformin levels.
Promptly discontinue treatment in patients experiencing hypoxic states, which may result from CV collapse (shock) from events such as acute CHF or acute MI.
Consider temporarily withholding therapy and administering insulin in patients who lose glycemic control as a result of fever, trauma, infection, or surgery.
Temporarily suspend therapy for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids). Do not restart until oral intake has resumed and renal function has been evaluated as normal.
Metformin may interfere with vitamin B 12 absorption from the B 12 -intrinsic factor complex.
Diarrhea, dizziness, headache, severe hypoglycemic reactions with coma, seizures, or other neurological impairment.
Copyright © 2009 Wolters Kluwer Health.