e 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 (seePRECAUTIONS). 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)*
*Events2% for the PRANDIN group in the placebo-controlled studies andevents in the placebo groupSee trial description in CLINICAL PHARMACOLOGY,Clinical TrialsEVENTPRANDINPLACEBOPRANDINSUN = 352N = 108N = 1228N = 498Placebo controlled studiesActive controlled studiesMetabolicHypoglycemia3171620RespiratoryURI1681010Sinusitis6234Rhinitis3378Bronchitis2167
GastrointestinalNausea5532Diarrhea
5246Constipation3223Vomiting3321Dyspepsia2242MusculoskeletalArthralgia6334Back Pain5467OtherHeadache111098Paresthesia3321Chest pain3121Urinary tract infection2133Tooth disorder20<1<1Allergy201<1
Cardiovascular Events
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) was1% 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
*glyburide and glipizidePRANDINSU*Total Exposed1228498Serious CV Events4%3%Cardiac Ischemic Events2%2%Deaths due to CV Events0.5%0.4%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 |
