492 Antidiobetics
6. Grunberger G. Quo vadis nateglinide? Ten-year perspective. Expert Opin Mitiglinide Calcium (r/NNMJ Pharmacother 2011; 12: 2097-2 106. Interactions cal�ica; The efficacy of nateglinide may be affected by other drugs Mitigiinidurn;KAD-1 229; Mitiglinida Mitig!lnide Adverse Effects and Precautions that have an independent effect on blood glucose. For more lviitigiinide Calcium Hydrate; S-21403; Kanbl;Yl>i details and examples of drugs that can increase or decrease As for Repaglinide, p. 497.2. blood-glucose concentrations, see Interactions under Sulfonylureas, p. 504.3. Incidence of adverse effects. A postmarketing cohort study collected adverse effect data for the first 6 months Reviews. 1. Scheen AJ. Drug-drug and food-drug pharmacokinetic interactions with after starting nateglinide in 4557 patients 1 Of these, 336 new insulinotropic <�gents repaglinide and nateglinidc. Clin Pharmaca (7.4%) used nateglinide alone, but the majority (76%) kinet 2007; 46: 93-108. were treated with nateglinide plus metformin. There were 80 adverse event reports attributed to nateglinide. Gastro Antibacterials. Rifampicin reduced the plasma concentra Profile intestinal disturbances were most common, particularly tions and half-life of nateglinide in healthy subjects, prob diarrhoea. There were 4 reports of hypersensitivity reac ably by induction of the cytochrome P450 isoenzyme Mitiglinide is a meglitinide antidiabetic (see Repaglinide, tions, presenting as pruritus or rash. Of the 45 reports of CYP2C9.1 The glucose-lowering effect of nateglinide was p. 497.2) that is used in the treatment of type 2 diabetes hypoglycaernia involving nateglinide, 5 patients were on not affected, but there was a marked interindividual varia I). mellitus (p. 459. Mitiglinide calcium is given in usual oral monotherapy, while the rest were also taking other tion in the pharmacokinetic changes, and the authors sug doses of 10 mg three time daily, immediately before meals. antidiabetics. Isolated reports that were assessed as prob gested that some diabetic patients could be affected. References. ably related to nateglinide included palpitations, Ray 1. Niemi M, et al. Eftect ol rifampicin on the pharmacokinetics and l. Yoshihara T, et al. Therapeutic efficacy of mitiglinide combined with naud's phenomenon, and oedema and fluid retention. pharmacodynamics of nateglinide in healthy subjects. Br J Clin once daily insulin glargine after switching from multiple daily insulin 56: 1. Twaites B, et al. Safety of nateglinide as used in general practice in Pharmacal 2003; 427-32. regimen of aspart insulin and glargine in patients with type 2 diabetes England: results of a prescription-event monitoring study. Acta Diabetal mellitus. Endocr J 2006; 53: 67-72. 2007; 44: 233-9. 2. Kumashiro N, et al. Long-term effect of combination therapy with Antifungals. Fluconazole raised the plasma concentrations mitiglinide and once daily insulin glargine in patients who were and prolonged the half-life of nateglinide in healthy sub switched from intensive insulin therapy in short-term Overdosage. A blood-glucose concentration of 2.0mmol! jects, probably by inhibition of its metabolism by the cyto 54: study. 163-6. litre was rneasured 1 hour after ingestion of nateglinide chrome P450 isoenzyme CYP2C9.1 The glucose-lowering 3. Yamada S, et a!. Effect of combination therapy of a rapid-acting insulin secretagogue (glinide) with premixed insulin in type 2 diabetes mellitus. 3.42 g in a 30-year-old woman 1 She was able to walk effect of nateglinide was not affected, but a low dose of Intern Med 2007; 46: 1893-7. unaided, but seemed drowsy. The hypoglycaemic effect of nateglinide had been used and the authors suggested that 4. Malaisse WJ . .Mitiglinide: a rapid- and short-acting non-sulfonylurea nateglinide lasted for 6 hours and was treated with intra in diabetic patients fluconazole may enhance and prolong treatment of type 2 diabetic patients. Expert venous glucose (total dose IOO g). the effects of nateglinide. Opin 9: 2691-8. 5. Kaku K, er al. Effect of mitiglinide on glycemic control over 52 weeks in I. Nakayama S, et al. Hypoglycemia following a nateglinide overdose in a phpioglitazone monothcrapy. 56: 739-46. 6. Gao X. Multicentrc, double-blind, randomized study of mitiglinide Porphyria. The Drug Database for Acute Porphyria, com Lipid regulating drugs. A study1 investigating the effects compared with nateglinide in type 2 diabetes mellitus patients in China. J Int Med Res 2009; 37: 812-21. piled by the Norwegian Porphyria Centre (NAPOS) and of the gemfibrozil and itraconazole combination on the phar 7. Abe M, et al. Efficacy and safety of mitiglinide in diabetic patients on the Porphyria Centre Sweden, classifies nateglinide as pos macokinetics of nateglinide showed only a limited interac maintenance hemodialysis. Endocr J 2010; 57: 579-86. sibly porphyrinogenic; it should be used only when no tion. Nateglinide plasma concentrations were raised mod 8. Phillippe HM, Wargo KA. Mitiglinide: a novel agent for the treatment of safer alternative is available and precautions should be erately and the blood glucose response to nateglinide was type 2 diabetes mellitus. Ann Pharmacather 2010; 44: 1615-23. considered in vulnerable patients. 1 not significantly changed. This is in contrast to the sub 1. The Drug Database for Acute Porphyria. Available at: http://www. stantial interaction of gemfibrozil with repaglinide P epa at ons drugs-porphyria.org (accessed 06/10/11) ...... r ...... r i...... (p. 498.2) . ProprietaryPreparations (details are given in Volume B) 1. Niemi M, et al. Coadministration of gemfibrozil and itraconazole has Pregnancy. Insulin is generally preferred to oral antidia only a minor effect on the pharmJcokinetics of the CYP2C9 and CYP3A4 Fa Ai Si (it:'t!IJi); Facti 60: Single-ingredient Preparations, China: betics in the treatment of diabetes mellitus during substrate nJteglinide. Br .JClin Pharmacal 2005; 208-17. (itill!); Glufast ('�Pn'li:);Jpn: Glufast; Thai.: Glufast. pregnancy. An analysis of postmarketing data found 2 Multi-ingredient Preparations. Jpn: Globes. reports of nateglinide use during pregnancy.1 In both cases Pharmacokinetics the drug was given in the first trimester only, with met Nateglinide is rapidly absorbed after oral doses and peak formin. One pregnancy resulted in a live birth with no plasma concentrations occur within one hour. It has an reported congenital abnormalities. In the other, nategli (USAN r/NN) absolute bioavailability of 73% and is 98% bound to plasma Nateglinide nide was stopped 3 months after the last menstrual period proteins. Nateglinide is mainly metabolised by cytochrome and replaced with metformin for the rest of the P450 isoenzyme CYP2C9, and to a lesser extent by CYP3A4. pregnancy; the baby was reported to have polycystic kid The major metabolites are less potent than nateglinide. The neys. parent drug and metabolites are mainly excreted in the I. Twaites B, et al. Safety of nateglinide as used in general practice in England: results of a prescription-event monitoring study. Acta Diabetol urine but about 10% is eliminated in the faeces. The 2007; 44: 233-9. elimination half-life is about 1.5 hours. References. Renal impairment. A single-dose pharmacokinetic study1 1. Choudhury S, et al. Single-dose of nateglinide in found that moderate to severe renal impairment ( creat subjects with hepatic cirrhosis. 40: 634--40. inine clearance 15 to 50mllminute per !.73 m2) and 2. Devineni D, et al. Pharmacokinetics of nateglinide in renally impaired diabetic patients. J Clin Pharmacal 2003; 43: 163-70. haemodialysis did not significantly affect the pharmacoki 3. McLeod .JF. Clinical pharmacokinetics of a rapidly- Pharmacopoeias. In Bur. see (p. vii) and US. netics of nateglinide. However, the metabolite Ml has absorbed, short-acting insulinotropic agent. Clin 2004; been found to accumulate after repeated doses of nategli 43: 97-120. Ph. Eur. 8: (Nateglinide). A white or almost white powder. nide in patients with renal impairment requiring haemo 4. Kirchheiner J, et al. Influence of CYP2C9 and CYP2D6 polymorphisms It exhibits polymorphism. Practically insoluble in water; MI on the pharmacokinetics of nateglinide in genotyped healthy dialysis, although haemodialysis removes it 2 is a volunteers. Clin Pharmacakinet 2004; 43: 267-78. freely soluble in methyl alcohol and in dichloromethane. major metabolite that has modest hypoglycaemic activity 5. Zhang W, et al. Effect of SLCOlBl genetic pol)rmo,rphism on the USP 36: (Nateglinide) . A white powder. Practically compared with nateglinide. An analysis' of pooled study pharmacokinetics of nateglinide. Br J Clin 62: 567-72. insoluble in water; freely soluble in alcohol and methyl data found that efficacy and tolerability of nateglinide in 6. Kalliokoski A, et a!. Different effects of" SLCOIB1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nategli alcohol; soluble in ether; sparingly soluble in acetonitrile elderly diabetic patients were not significantly affected by nide . .JClin Pharmacal 2008; 48: 311-21. and octanol. Store in airtight containers. renal impairment (mean creatinine clearance 50.9mL/miM nute per !. 73 m2). Nevertheless, a 56-year-old diabetic r �r ti Uses and Administration woman whose renal failure was managed with haemodia M P. �p � ".n.� . lysis developed severe hypoglycaemia with nateglinide; ProprietaryPreparations (details are given in Volume B) Nateglinide, like repaglinide (p. 497.2), is a meglitinide the reaction was attributed to the accumulation of Ml.4 Nateglint; Starlix; antidiabetic used in the treatment of type 2 diabetes mellitus Severe hypoglycaemia, attributed to therapeutic doses of SingleMingredient Preparations. Arg.: Braz.: Starlix; Canad. : Starlix; Chile: Gluconol; StarHx; China: (p. 459.I). It is given within the 30 minutes before meals in nateglinide, also occurred in a 73-year-old diabetic oral doses of 60 or 120mg three times daily. This may be Antangping Bei Jia Cankexin woman "With chronic renal failure managed with haemo ChangTai Danping (fH"l:Di Fang Fei Ge Na increased to 180mg three times daily if necessary. 5 ('!thiazolidinedione in type 2 diabetes not adequately :lGt�); (5€-Piti!J); (nJ$;); ment. Licensed produc_t information in the UK and USA Ling (m!/!1);(Jl!f"i'); Tang Na(:7'' hlli); Tang (1'1'Rui;11' ); Tang Yi controlled by these drugs alone. suggest that no dosage adjustment is necessary in renal Wan Su Xin Xi Rui Ya Li Ding I'Ti'J'LtJ);Yi Ke Although dose adjustment is not generally required in (fili]p); (Jil!Jil\i); (lit$,); impairment, although UK information suggests that dose Xian (Ji;)}rrJo:Yi Ke Ya Xin (#>lw): Yi You Li An (S\1Jt5fU renal impairment, serious hypoglycaemia has occurred in adjustment might be required in patients on haemodia �); Cz.(�1'1Tfil: Starlix;l); Trazect; Fin.:(J\\ Starlixt;J'ii[i[.l:); Ger.: Starlix; Gr.: Star patients with chronic renal failure (see p. 494.2). lysis. lix; Hung.: Starlix; India: Glinate-MF; Glinate; Natelide; References. I. Devineni D, et al. Pharmacokinetics of nateglinide in renally impaired Indon.: Starlix; Irl.: Starlix; Jpn: Starsis; Malaysia: Starlix; Dunn CJ, Faulds D. Nateglinide. Drugs 2000; 60: 607-15. diabetic patients. J Clin Phannacal 2003; 43: 163-70. Starlix; Starlix; Starlix; Starlix; L Mex. : Neth.: Norw. : Philipp.: 2. Hanefeld M, et al. Rapid and short-acting mealtime insulin secretion 2. Inoue T, et al. Pharmacokinetics of nateglinide and its metabolites in Pol.: Starlix; Port.: Starlix; Rus.: Starlix (CmpnHKc); S.A.fr. : Star with natcglinide controls both prandial and mean glycemia. Diabetes Care subjects with 2 diabetes mellitus and renal failure. Clin Nephrol lix; Singapore: Starlix; Spain: Starlix; Swed.: Starlix; Switz. : 23: 60: 2000; 202-7. 2003; Starlix; Turk.: Incuria; Mecosyn; Starlix; Teglix; UK: Starlix; 3. Levien TL, et al. NategliJ.1ide therapy for type 2 diabetes mellitus. Ann 3. Del Prato S, et a!. Treatment of patients over 64 years of age with type 2 Pharmacather 2001; 35: 1426-34. diabetes: from nateglinide pooled database retrospective USA: Starlix; Venez. : Starlix. 4. Black C, et al. Meglitinide analogues for type 2 diabetes mellitus. analysis. Care 2003; 26: 2075-80. Available in The Cochrane Database of Systematic Reviews; Issue 2. 4. Nagai T, et at. Hypoglycemia due to nateglinide administration in Multi-ingredient Preparations. Braz. : Starform; Venez. : Starform. Chichester: John Wiley; 2007 (accessed 03/04/09). diabetic patient with chronic renal failure. Diabetes Res Clin Prad 2003; 5. Holman RR, et a!. NAVIGATOR Study Group. Effect of nateglinide on the 59: 191-4. Pharmacopoeial Preparations incidence of diabetes and cardiovascular events. N Engl J Med 2010; 362: 5. Sherk DK, Bryant SM. Octreotide therapy for nateglinide-induced USP 36: Nateglinide Tablets. 1463-76. Correction. ibid.; 1748. hypoglycemia. Ann b'mergMed 2007; 50: 745-6.
All crossMreferences refer to entries in Volume A
