Repaglinide - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Hypoglycemia : Repaglinide may cause hypoglycemia.

Skip the scheduled dose of repaglinide if a meal is skipped to reduce the risk of hypoglycemia.

Reduce the dose of repaglinide if hypoglycemia occurs.

Serious Cardiovascular Adverse Reactions with Concomitant NPH-insulin : Repaglinide is not indicated for use in combination with NPH-insulin.

Macrovascular outcomes : There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with repaglinide.

5.1 Hypoglycemia All glinides, including repaglinide, can cause hypoglycemia [see Adverse Reactions ] .

Severe hypoglycemia can cause seizures, may be life-threatening, or cause death.

Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual.

Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ] , or in patients who experience recurrent hypoglycemia.

Factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content), changes in level of physical activity, changes to co-administered medication [see Drug Interactions ] , and concomitant use with other antidiabetic agents.

Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6 , 8.7) ] .

Patients should administer repaglinide before meals and be instructed to skip the dose of repaglinide if a meal is skipped.

In patients who experience hypoglycemia, the dose of repaglinide should be reduced [see Dosage and Administration ] .

Patients and caregivers must be educated to recognize and manage hypoglycemia.

Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia.

In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.

5.2 Serious Cardiovascular Adverse Reactions with Concomitant Use with NPH-insulin Across seven controlled trials, there were six serious adverse events of myocardial ischemia in patients treated with repaglinide plus NPH-insulin from two studies, and one event in patients using insulin formulations alone from another study [See Adverse Reactions ] .

Repaglinide is not indicated for use in combination with NPH-insulin.

5.3 Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with repaglinide.