Repaglinide

5.9

3.2

2.94e-03 g/L

>67.9 [ug/mL] (The mean of the results at pH 7.4)

Breast Feeding; Lactation; Milk, Human; Hypoglycemic Agents

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

130-131 °C

130 - 131 °C

Warning

H361 (96.7%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

P203, P260, P263, P264, P270, P273, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 60 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In several large clinical trials, serum aminotransferase elevations during repaglinide therapy were uncommon and similar in frequency with placebo. All serum enzyme elevations that occurred were asymptomatic and resolved rapidly with stopping therapy. Since its approval and with wide scale use, there have been a small number of reports of clinically apparent liver injury attributed to repaglinide. The time to onset ranged from 2 to 8 weeks and the pattern of serum enzyme elevations was typically cholestatic or mixed. Jaundice and pruritus were prominent. Immunoallergic features and autoantibodies were not present. All published cases have been self-limited, resolving within 1 to 2 months of stopping.

The most commonly reported side effect associated with repaglinide monotherapy is hypoglycemia (7% in a study of 76 patients), followed by weight gain (1.8 kg / 16 weeks). Whipple triad for hypoglycemia is defined as the presence of symptoms of hypoglycemia, presence of factual hypoglycemia (Repaglinide has reports showing it to be of greater risk of cardiovascular events than metformin but lesser than sulfonylureas.

A10BX02

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.

Repaglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Repaglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.