tion
Not known: Nausea
Gastro-intestinal complaints such as abdominal pain, diarrhoea, nausea, vomiting and constipation have been reported in clinical trials. The rate and severity of these symptoms did not differ from that seen with other oral insulin secretagogues.
Skin and subcutaneous tissue disorders
Not known: Hypersensitivity
Hypersensitivity reactions of the skin may occur as erythema, itching, rashes and urticaria. There is no reason to suspect cross-allergenicity with sulphonylurea drugs due to the difference of the chemical structure.
Eye disorders
Very rare: Visual disturbances
Changes in blood glucose levels have been known to result in transient visual disturbances, especially at the commencement of treatment. Such disturbances have only been reported in very few cases after initiation of repaglinide treatment. No such cases have led to discontinuation of repaglinide treatment in clinical trials.
Cardiac disorders
Rare: Cardiovascular disease
Type 2 diabetes is associated with an increased risk for cardiovascular disease. In one epidemiological study, a higher incidence of acute coronary syndrome was reported in the repaglinide group. However, the causality of the relationship remains uncertain (see sections 4.4 and 5.1).
Hepato-biliary disorders
Very rare: Hepatic function abnormal
In very rare cases, severe hepatic dysfunction has been reported. However, a causal relationship with repaglinide has not been established.
Very rare: Increased liver enzymes
Isolated cases of increase in liver enzymes have been reported during treatment with repaglinide. Most cases were mild and transient, and very few patients discontinued treatment due to increase in liver enzymes.
4.9 Overdose
Repaglinide has been given with weekly escalating doses from 4 - 20 mg four times daily in a 6 week period. No safety concerns were raised. As hypoglycaemia in this study was avoided through increased calorie intake, a relative overdose may result in an exaggerated glucose-lowering effect with development of hypoglycaemic symptoms (dizziness, sweating, tremor, headache etc.). Should these symptoms occur, adequate action should be taken to correct the low blood glucose (oral carbohydrates). More severe hypoglycaemia with seizure, loss of consciousness or coma should be treated with IV glucose.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmaco-therapeutic group: Carbamoylmethyl benzoic acid derivative, ATC code: A10B X02
Repaglinide is a novel short-acting oral secretagogue. Repaglinide lowers the blood glucose levels acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning β-cells in the pancreatic islets.
Repaglinide closes ATP-dependent potassium channels in the β-cell membrane via a target protein different from other secretagogues. This depolarises the β-cell and leads to an opening of the calcium channels. The resulting increased calcium influx induces insulin secretion from the β-cell.
In type 2 diabetic patients, the insulinotropic response to a meal occurred within 30 minutes after an oral dose of repaglinide. This resulted in a blood glucose-lowering effect throughout the meal period. The elevated insulin levels did not persist beyond the time of the meal challenge. Plasma repaglinide levels decreased rapidly, and low drug concentrations were see
