Drug Approvals
(US Adopted Name, rINN)
INNs in other languages:
Adverse Effects and Precautions
As for Repaglinide.
Overdosage. A blood-glucose concentration of 2.0 mmol/litre was measured 1 hour after ingestion of nateglinide 3.42 g in a 30-year-old woman. She was able to walk unaided, but seemed drowsy. The hypoglycaemic effect of nateglinide lasted for 6 hours and was treated with intravenous glucose (total dose 100 g).
Renal impairment. A single-dose pharmacokinetic studyfound that moderate to severe renal impairment (creatinine clearance 15 to 50 mL/minute per 1.73 m) and haemodialysis did not significantly affect the pharmacokinetics of nateglinide. However, the metabolite Ml has been found to accumulate in patients with renal impairment requiring haemodialysis after repeated doses of nateglinide, but it may be removed by haemodialysis. M1 is a maj or metabolite that has modest hypoglycaemic activity compared with nateglinide. An analysis of pooled study data found that efficacy and tolerability of nateglinide in elderly diabetic patients were not significantly affected by renal impairment (mean creatinine clearance 50.9 mL/minute per 1.73 m). Nevertheless, a 56-year-old diabetic woman whose renal failure was managed with haemodialysis experienced severe hypoglycaemia with nateglinide the reaction was attributed to the accumulation of M1 Licensed product information in the UK and USA suggest that no dosage adjustment is necessary in renal impairment, although UK information suggests that dose adjustment might be required in patients on haemodialysis.
Interactions
As with other oral antidiabetics, the efficacy of nateglinide may be affected by drugs independently increasing or decreasing blood glucose concentrations (see Sulfonylureas).
Antibacterials. In a study of healthy subjects, rifampicin reduced the plasma concentrations and half-life of nateglinide, probably by induction of its metabolism by the cytochrome P450 isoenzyme CYP2C9. The glucose-lowering effect of nateglinide was not affected, but there was a marked interindividual variation in the pharmacokinetic changes, and the authors suggested that some diabetic patients could be affected.
Antifungals. In a study of healthy subjects, fluconazole raised the plasma concentrations and prolonged the half-life of nateglinide, probably by inhibition of its metabolism by the cytochrome P450 isoenzyme CYP2C9. The glucose-lowering effect of nateglinide was not affected, but a low dose of nateglinide had been used and the authors suggested that in diabetic patients fluconazole may enhance and prolong the effects of nateglinide.
Lipid regulating drugs. A study investigating the effects of the gemfibrozil and itraconazole combination on the pharmacokinetics of nateglinide showed only a limited interaction. Nateglinide plasma concentrations were raised moderately and the blood glucose response to nateglinide was not significantly changed. This is in contrast to the substantial interaction of gemfibrozil with repaglinide.
Pharmacokinetics
Nateglinide is rapidly absorbed after oral doses, with peak plasma concentrations occurring within one hour and an absolute bioavailability of 73%. Nateglinide is 98% bound to plasma proteins. It is mainly metabolised by cytochrome P450 isoenzyme CYP2C9, and to a lesser extent by CYP3A4. Major metabolites include Ml which is less potent than nateglinide. The parent drug and metabolites are mainly excreted in the urine but about 10% is eliminated in the faeces. The elimination half-life is about 1.5 hours.
Uses and Administration
Nateglinide, like repaglinide, is a meglitinide antidiabetic used in the treatment of type 2 diabetes mellitus. It is given within the 30 minutes before meals in oral doses of 60 or 120 mg three times daily. This may be increased to 180 mg three times daily if necessary. Nateglinide is also given in similar doses with metformin or a thiazolidinedione in type 2 diabetes not adequately controlled by these drugs alone. Although dose adjustment is not generally required in renal impairment, hypoglycaemia has been attributed to accumulation of the metabolite M1 (see above).
Preparations
Proprietary Preparations
Argentina: Nateglin Starlix
Brazil: Starlix
Canada: Starlix
Chile: Gluconol Starlix
Czech Republic: Starlix Trazec
Denmark: Starlix †
Finland: Starlix
Germany: Starlix
Greece: Starlix
Hong Kong: Starlix!
Hungary: Starlix
India: Glinate
Indonesia: Starlix
Ireland: Starlix
Japan: Starsis
Malaysia: Starlix
Mexico: Starlix
The Netherlands: Starlix Trazec
Norway: Starlix
New Zealand: Starlix †
Philippines: Starlix
Portugal: Starlix Trazec
Russia: Starlix
South Africa: Starlix
Singapore: Starlix
Spain: Starlix
Sweden: Starlix
Switzerland: Starlix
Turkey: Starlix
UK: Starlix
USA: Starlix
Multi-ingredient
Brazil: Starform
Venezuela: Starform