Allopurinol adversely affected glycaemic control in a patient withtype 2 diabetes receiving insulin. Allopurinol caused an increasein half-life of chlorpropamide, and a minor decrease in thehalf-life of tolbutamide, but effect of these changes on hypoglycaemic response of patients is uncertain. Marked hypoglycaemia and coma occurred in one patient taking gliclazide andallopurinol.
A case report describes improved glycaemic control in a type 2 diabetic patient after allopurinol was stopped. Despite restricted food intake and an increasing dose of insulin, his glycaemic control was poor (fasting blood glucose 14.8 mmol/L) when he took allopurinol 100mg twice daily. However, within a few days of stopping allopurinol, an unexpected improvement in glycaemic control was observed (fasting blood glucose reduced to less than 11 mmol/L). He was later rechallenged with allopurinol,which resulted in reduced glucose tolerance, but increased insulin response, suggesting increased insulin resistance. Hyperuricaemia was later controlled with probenecid, which did not adversely affect glycaemic control (See reference number 1).
A brief report describes 6 patients taking chlorpropamide with allopurinol. The half-life of chlorpropamide in one patient with gout and normal renal function exceeded 200 hrs (normally 36 hours) after allopurinol had been taken for 10 days, and in 2 others half-life was extended to 44 and 55 hours. The other 3 patients were given allopurinol for only 1 or 2 days and half-life of chlorpropamide remained unaltered (See reference number 2).
Severe hypoglycaemia (1.6 mmol/L) and coma occurred in a patient with renal impairment taking gliclazide and allopurinol (See reference number 3). Hypoglycaemia has been seen in another patient taking both drugs,but an interaction is less clear, as enalapril and ranitidine, which may also (rarely) interact were also involved (See reference number 3).
Allopurinol 2.5 mg/kg twice daily for 15 days reduced half-life of intravenous tolbutamide in 10 healthy subjects by 25%, from 360 to 267 minutes (See reference number 4,5).
In case of chlorpropamide it has been suggested that it possibly involves some competition for renal tubular mechanisms (See reference number 2)
Information is very limited. Only gliclazide has been implicated in severe hypoglycaemia with allopurinol and there seem to be no reports of either grossly enhanced hypoglycaemia with chlorpropamide and allopurinol,or a reduced effect with tolbutamide and allopurinol. More study is needed to find out whether any of these interactions has general clinical importance,but it seems unlikely.
Ohashi K,Ishibashi S, Yazaki Y, Yamada N. Improved glycemic control in a diabetic patientafter discontinuation of allopurinol administration. Diabetes Care (1998) 21, 192–3.
Petitpierre B,Perrin L, Rudhardt M, Herrera A, Fabre J. Behaviour of chlorpropamide in renalinsufficiency and under the effect of associated drug therapy. Int J Clin Pharmacol (1972) 6, 120–4.
Girardin E,Vial T, Pham E, Evreux J-C. Hypoglycémies induites par les sulfamides hypoglycémiants. Ann Med Interne (Paris) (1992) 143, 11–17.
Gentile S,Porcellini M, Loguercio C, Foglia F, Coltorti M. Modificazioni della depurazioneplasmatica di tolbutamide e rifamicina-SV indotte dal trattamento con allopurinolo in volontari sono. Progr Med (Napoli) (1979) 35, 637–42.
Gentile S,Porcellini M, Foglia F, Loguercio C, Coltorti M. Influenza di allopurinolo sull’emivita plasmatica di tolbutamide e rifamicina-SV in soggetti sani. Boll Soc Ital Biol Sper (1979) 55, 345–8.