PRANDIMET SIDE EFFECTS
- Generic Name: repaglinide and metformin hcl tablets
- Brand Name: Prandimet
SIDE EFFECTS
Most Frequently Observed Adverse Reactions
Repaglinide
In clinical trials of repaglinide, hypoglycemia is the most common adverse reaction (> 5%) leading to withdrawal of patients treated with repaglinide.
Metformin HCl
Gastrointestinal reactions (e.g., diarrhea, nausea, vomiting) are the most common adverse reactions (> 5%) with metformin HCl treatment and are more frequent at higher metformin HCl doses.
Clinical Trial Experience
Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Patients with Inadequate Glycemic Control on Metformin HCl Monotherapy
Table 1 summarizes the most common adverse reactions occurring in a 6-month randomized study of repaglinide added to metformin HCl in patients with type 2 diabetes inadequately controlled on metformin HCl alone.
Table 1: Repaglinide added to metformin HCl in patients with type 2 diabetes inadequately controlled on metformin HCl alone. Adverse reaction reported (regardless of Investigator Assessment of Causality) in ≥10% of patients receiving combination therapy*
| Coadministered repaglinide and metformin HCl N (%) |
Metformin HCl monotherapy N (%) |
Repaglinide monotherapy N (%) |
|
| No. of Patients Exposed | 27 | 27 | 28 |
| Gastrointestinal System Disorder | 9 (33) | 13 (48) | 10 (36) |
| Diarrhea | 5 (19) | 8 (30) | 2 (7) |
| Nausea | 4 (15) | 2 (7) | 1 (4) |
| Symptomatic Hypoglycemia ** | 9 (33) | 0 (0) | 3 (11) |
| Headache | 6 (22) | 4 (15) | 3 (11) |
| Upper Respiratory Tract Infection | 3 (11) | 3 (11) | 3 (11) |
| *Intent to treat population ** There were no cases of severe hypoglycemia (hypoglycemia requiring the assistance of another person) |
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Cardiovascular Events in repaglinide monotherapy trials
In one-year trials comparing repaglinide to sulfonylurea drugs, the incidence of angina was 1.8% for both treatments, with an incidence of chest pain of 1.8% for repaglinide and 1.0% for sulfonylureas. The incidence of other selected cardiovascular events (hypertension, abnormal electrocardiogram, myocardial infarction, arrhythmias, and palpitations) was ≤ 1% and not different between repaglinide and the comparator drugs.
The incidence of total serious cardiovascular adverse events, including ischemia, was higher for repaglinide (51/1228 or 4%) than for sulfonylurea drugs (13/498 or 3%) in controlled clinical trials. In 1-year controlled trials, repaglinide treatment was not associated with excess mortality when compared to the rates observed with other oral hypoglycemic agent therapies such as glyburide and glipizide.
Seven controlled clinical trials included repaglinide combination therapy with NPH-insulin (n=431), insulin formulations alone (n=388) or other combinations (sulfonylurea plus NPH-insulin or repaglinide plus metformin HCl) (n=120). There were six serious adverse events of myocardial ischemia in patients treated with repaglinide plus NPH-insulin (1.4%) from two studies, and one event in patients using insulin formulations alone from another study (0.3%).
Postmarketing Experience
Repaglinide
The following additional adverse reactions have been identified during postapproval use of repaglinide. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or a causal relationship to drug exposure.
Postmarketing experience with repaglinide includes infrequent reports of the following adverse events; alopecia, hemolytic anemia, pancreatitis, Stevens-Johnson Syndrome, and severe hepatic dysfunction including jaundice and hepatitis.
SRC: NLM .