od glucose-lowering drugs (naor whose HbA1c is less than 8%. PRANDIN should be administered with meals to lessen the risk of hypoglycemia.
Loss of Control of Blood Glucose:When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of glycemic control may occur. At such times, it may be necessary to discontinue PRANDIN and administer insulin. The effectiveness of any hypoglycemic drug in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of diabetes or to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when the drug is first given. Adequate adjustment of dose and adherence to diet should be assessed before classifying a patient as a secondary failure.
INFORMATION FOR PATIENTS
Patients should be informed of the potential risks and advantages of PRANDIN and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose and HbA1c. The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development and concomitant administration of other glucose-lowering drugs should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
Patients should be instructed to take PRANDIN before meals (2, 3, or 4 times a day preprandially).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. Patients who skip a meal (or add an extra meal) should be instructed to skip (or add) a dose for that meal.
LABORATORY TESTS
Response to all diabetic therapies should be monitored by periodic measurements of fasting blood glucose and glycosylated hemoglobin levels with a goal of decreasing these levels towards the normal range. During dose adjustment, fasting glucose can be used to determine the therapeutic response. Thereafter, both glucose and glycosylated hemoglobin should be monitored. Glycosylated hemoglobin may be especially useful for eva luating long-term glycemic control. Postprandial glucose level testing may be clinically helpful in patients whose pre-meal blood glucose levels are satisfactory but whose overall glycemic control (HbA1c) is inadequate.
DRUG INTERACTIONS
In vitro data indicate that PRANDIN is metabolized by cytochrome P450 enzymes 2C8 and 3A4. Consequently, repaglinide metabolism may be altered by drugs which influence these cytochrome P450 enzyme systems via induction and inhibition. Caution should therefore be used in patients who are on PRANDIN and taking inhibitors and/or inducers of CYP2C8 and CYP3A4. The effect may be very significant if both enzymes are inhibited at the same time resulting in a substantial increase in repaglinide plasma concentrations. Drugs that are known to inhibit CYP3A4 include antifungal agents like ketoconazole, itraconazole, and antibacterial agents like erythromycin. Drugs that are known to inhibit CYP2C8 include agents like trimethoprim, gemfibrozil and montelukast. Drugs that induce the CYP3A4 and/or 2C8 enzyme systems include rifampin, barbiturates, and carbamezapine. See CLINICAL PHARMACOLOGY section,Drug-Drug Interactions. |
