Nateglinide Other names: Nateglynide

Data available from both in vitro and in vivo experiments indicate that nateglinide is predominantly metabolised by CYP2C9 with involvement of CYP3A4 to a smaller extent.

In an interaction trial with sulfinpyrazone, a CYP2C9 inhibitor, a modest increase in nateglinide AUC (~28%) was observed in healthy volunteers, with no changes in the mean C_max and elimination half-life. A more prolonged effect and possibly a risk of hypoglycaemia cannot be excluded in patients when nateglinide is co-administered with CYP2C9 inhibitors.

Particular caution is recommended when nateglinide is co-administered with other more potent inhibitors of CYP2C9 (e.g. fluconazole, gemfibrozil or sulfinpyrazone), or in patients known to be poor metabolisers for CYP2C9 substrates.

The following agents may reduce the hypoglycaemic effect of nateglinide: diuretics, corticosteroids, beta2 agonists, somatropin, somatostatin analogues (e.g. lanreotide, octreotide), rifampin, phenytoin and St. John’s Wort (Hypericum perforatum).

When these medicinal products – that reduce the hypoglycaemic effect of nateglinide – are administered to or withdrawn from patients receiving nateglinide, the patient should be observed closely for changes in glycaemic control.

The following agents may enhance the hypoglycaemic effect of nateglinide: Angiotensin-converting enzyme inhibitors (ACEI), non-steroidal anti-inflammatory agents, salicylates, monoamine oxidase inhibitors, non-selective beta-adrenergic-blocking agents and anabolic hormones (e.g. methandrostenolone).

When these medicinal products – that enhance the hypoglycaemic effect of nateglinide – are administered to or withdrawn from patients receiving nateglinide, the patient should be observed closely for changes in glycaemic control.

Combination with metformin is associated with an increased risk of hypoglycaemia compared to monotherapy.

Studies in animals have shown developmental toxicity. There is no experience in pregnant women, therefore the safety of nateglinide in pregnant women cannot be assessed. Nateglinide, like other oral antidiabetic agents, must not be used in pregnancy.

Nateglinide is excreted in the milk following a peroral dose to lactating rats. Although it is not known whether nateglinide is excreted in human milk, the potential for hypoglycaemia in breast-fed infants may exist and therefore nateglinide should not be used in lactating women.

Fertility

Nateglinide did not impair fertility in male or female rats.

The effect of nateglinide on the ability to drive or operate machinery has not been studied. Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.