Gastro-intestinal disorders

Common: Abdominal pain and diarrhoea

Very rare: Vomiting and constipation

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 differen