"The U.S. Food and Drug Administration today approved Jardiance (empagliflozin) tablets as an addition to diet and exercise to improve glycemic control in adults with type 2 diabetes.
Type 2 diabetes affects approximately 26 million people a"...
See PRECAUTIONS and OVERDOSAGE sections. PRANDIN has been administered to 2931 individuals during clinical trials. Approximately 1500 of these individuals with type 2 diabetes have been treated for at least 3 months, 1000 for at least 6 months, and 800 for at least 1 year. The majority of these individuals (1228) received PRANDIN in one of five 1-year, active-controlled trials. The comparator drugs in these 1-year trials were oral sulfonylurea drugs (SU) including glyburide and glipizide. Over one year, 13% of PRANDIN patients were discontinued due to adverse events, as were 14% of SU patients. The most common adverse events leading to withdrawal were hyperglycemia, hypoglycemia, and related symptoms (see PRECAUTIONS). Mild or moderate hypoglycemia occurred in 16% of PRANDIN patients, 20% of glyburide patients, and 19% of glipizide patients.
The table below lists common adverse events for PRANDIN patients compared to both placebo (in trials 12 to 24 weeks duration) and to glyburide and glipizide in one year trials. The adverse event profile of PRANDIN was generally comparable to that for sulfonylurea drugs (SU).
Commonly Reported Adverse Events (% of Patients)*
N = 352
N = 108
N = 1228
N = 498
|Placebo controlled studies||Active controlled studies|
|Urinary tract infection||2||1||3||3|
|Tooth disorder||2||0||< 1||< 1|
|*: Events ≥ 2% for the PRANDIN group in the
placebo-controlled studies and ≥ events in the placebo group
**: See trial description in CLINICAL PHARMACOLOGY, Clinical Trials
In one-year trials comparing PRANDIN to sulfonylurea drugs, the incidence of angina was comparable (1.8%) for both treatments, with an incidence of chest pain of 1.8% for PRANDIN and 1.0% for sulfonylureas. The incidence of other selected cardiovascular events (hypertension, abnormal EKG, myocardial infarction, arrhythmias, and palpitations) was ≤ 1% and not different between PRANDIN and the comparator drugs.
The incidence of total serious cardiovascular adverse events, including ischemia, was higher for repaglinide (4%) than for sulfonylurea drugs (3%) in controlled comparator clinical trials. In 1 year controlled trials, PRANDIN treatment was not associated with excess mortality when compared to the rates observed with other oral hypoglycemic agent therapies.
Summary of Serious Cardiovascular Events (% of total
patients with events) in Trials Comparing PRANDIN to Sulfonylureas
|Serious CV Events||4%||3%|
|Cardiac Ischemic Events||2%||2%|
|Deaths due to CV Events||0.50%||0.40%|
|*: glyburide and glipizide|
Seven controlled clinical trials included PRANDIN combination therapy with NPH-insulin (n=431), insulin formulations alone (n=388) or other combinations (sulfonylurea plus NPH-insulin or PRANDIN plus metformin) (n=120). There were six serious adverse events of myocardial ischemia in patients treated with PRANDIN plus NPH-insulin from two studies, and one event in patients using insulin formulations alone from another study.
Infrequent Adverse Events ( < 1% of Patients)
Less common adverse clinical or laboratory events observed in clinical trials included elevated liver enzymes, thrombocytopenia, leukopenia, and anaphylactoid reactions.
Although no causal relationship with repaglinide has been established, postmarketing experience includes reports of the following rare adverse events: alopecia, hemolytic anemia, pancreatitis, Stevens-Johnson Syndrome, and severe hepatic dysfunction including jaundice and hepatitis.
Combination Therapy with Thiazolidinediones
During 24-week treatment clinical trials of PRANDIN-rosiglitazone or PRANDIN-pioglitazone combination therapy (a total of 250 patients in combination therapy), hypoglycemia (blood glucose < 50 mg/dL) occurred in 7% of combination therapy patients in comparison to 7% for PRANDIN monotherapy, and 2% for thiazolidinedione monotherapy.
Peripheral edema was reported in 12 out of 250 PRANDIN-thiazolidinedione combination therapy patients and 3 out of 124 thiazolidinedione monotherapy patients, with no cases reported in these trials for PRANDIN monotherapy. When corrected for dropout rates of the treatment groups, the percentage of patients having events of peripheral edema per 24 weeks of treatment were 5% for PRANDIN-thiazolidinedione combination therapy, and 4% for thiazolidinedione monotherapy. There were reports in 2 of 250 patients (0.8%) treated with PRANDINthiazolidinedione therapy of episodes of edema with congestive heart failure. Both patients had a prior history of coronary artery disease and recovered after treatment with diuretic agents. No comparable cases in the monotherapy treatment groups were reported.
Mean change in weight from baseline was +4.9 kg for PRANDIN-thiazolidinedione therapy. There were no patients on PRANDIN-thiazolidinedione combination therapy who had elevations of liver transaminases (defined as 3 times the upper limit of normal levels).
Read the Prandin (repaglinide) Side Effects Center for a complete guide to possible side effects
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.
Repaglinide appears to be a substrate for active hepatic uptake transporter (organic anion transporting protein OATP1B1). Drugs that inhibit OATP1B1 (e.g. cyclosporine) may likewise have the potential to increase plasma concentrations of repaglinide. See CLINICAL PHARMACOLOGY section, Drug-Drug Interactions.
In vivo data from a study that evaluated the co-administration of a cytochrome P450 enzyme 3A4 inhibitor, clarithromycin, with PRANDIN resulted in a clinically significant increase in repaglinide plasma levels. In addition, an increase in repaglinide plasma levels was observed in studies that evaluated the co-administration of PRANDIN with trimethoprim and PRANDIN with deferasirox, both cytochrome P-450 enzyme 2C8 inhibitors. These increases in repaglinide plasma levels may necessitate a PRANDIN dose adjustment. See CLINICAL PHARMACOLOGY section, Drug-Drug Interactions.
The hypoglycemic action of oral blood glucose-lowering agents may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, cyclosporine, chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving oral blood glucose-lowering agents, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving oral blood glucose-lowering agents, the patient should be observed closely for loss of glycemic control.
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When these drugs are administered to a patient receiving oral blood glucose-lowering agents, the patient should be observed for loss of glycemic control. When these drugs are withdrawn from a patient receiving oral blood glucose-lowering agents, the patient should be observed closely for hypoglycemia.
Read the Prandin Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/14/2012
This monograph has been modified to include the generic and brand name in many instances.
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