Cimetidine can increase the hypoglycaemic effects of gltptzide, gliclazide and possibly ghbenclamide in diabetics and there is the risk of excessive hypoglycaemta Ranitidine appears to behave similarly. The clinical relevance of other studies in normal subjects is uncertain some report that no significant interactions occur in normal subjects with tolbutamide, ghbenclamide, chlorpropamide or ghpizide and cimetidine, whereas one says that the effects of ghbenclamide are reduced by cimetidine and ranitidine. Cimehdine increases the serum levels of Glucophage.

Clinical evidence
Studies in diabetic patients given sulphonylureas
Six diabetics were given 400 mg cimetidine 1 h before taking a dose of ghpizide (average 5 7 mg dose) and then 3 h later they were given a standard meal with 200 mg of cimetidine. The expected rise in blood sugar levels after the meal was reduced by 40% and m three of the patients it fell to less than 3 mmol/1. In another report an elderly diabetic taking 160 mg ghpizide daily developed very low blood sugar levels (1 mmol/1) after starting treatment with 800 mg cimetidine daily. A study in diabetics mdicated that ranitidine can also increase the effects of ghpizide. Marked hypoglycaemia was seen in a patient on ghbenclamide when treated with ranitidine.

Studies in normal subjects given sulphonylureas
A study in seven subjects, given 250 mg tolbutamide daily for four days, showed that when additionally given 800 mg cimetidine daily for a further four days the pharmacokinetics of the tolbutamide were not significantly changed. Another study found no interaction between tolbutamide and cimetidine. Other studies in normal subjects showed that 800 mg cimetidine daily for seven days had no significant effect on the serum levels or the pharmacokinetics of tolbutamide or chlorpropamide. The hypoglycaemic activities of tolbutamide, chlorpropamide, glibendamide and ghpizide remained unaltered. In contrast in another study the AUC of tolbutamide was found to be increased by 20% and the elimination half life decreased by 17% by 1200 mg cimehdme, but plasma glucose levels were not significantly changed Ranitidine had no effect. Yet another study reported that the hypoglycaemic effects of ghbenclamide were reduced by cimetidine and ranitidine

Study in normal subjects given a biguamde
800 mg cimetidine daily was found to reduce the renal clearance of Glucophage in seven normal subjects by 27% and increase the AUC by 50% .

Mechanism
If an interaction occurs it may be because the cimetidine inhibits the metabolism of the sulphonylurea by the liver, thereby increasing its effects Cimetidine appears to inhibit the excretion of Glucophage by the kidneys.

Importance and management
Information is limited and difficult to assess because of the differences between the sulphonylureas and between normal subjects and diabetics. Cimetidine and raruhdine are probably best avoided in diabetics taking glibenclarrude, ghpizide or gliclazide because of the risk of excessive hypoglycaerrua unless the effects can be well monitored Whether this is equally true for other sulphonylureas is less clear but certainly diabetics should be warned to watch for any evidence of hypoglycaemia or hyperglycaemia if cimetidine or ranitidine is added or withdrawn. More study is needed.

The Glucophage dosage may need to be reduced if cimetidme is used, bearing in mind the possibility of lactic acidosis if levels become too high It is uncertain whether other H2-blockers interact similarly.

glucophage.co.uk