Studies in diabetics have shown that chloramphenicol 2 g daily can increase serum level and half-life of tolbutamide twofold, and two to threefold, respectively (See reference number 1,2). Blood glucose levels were reduced by about 25 to 30 % (See reference number 2,3). Hypoglycaemia,acute in one case, developed in two other patients taking tolbutamide with chloramphenicol (See reference number 4,5). In another study chloramphenicol 1 to 2 g daily caused an average twofold increase in half-life of chlorpropamide (See reference number 6).
Chloramphenicol inhibits liver enzymes concerned with metabolism of tolbutamide, and probably chlorpropamide as well, leading to their accumulation in body. This is reflected in prolonged half-lives,reduced blood glucose levels and occasionally acute hypoglycaemia (See reference number 1-4,6).
The interaction between tolbutamide and chloramphenicol is well established and of clinical importance. The incidence is uncertain,but increased blood glucose-lowering effects should be expected if both drugs are given. The interaction between chlorpropamide and chloramphenicol is less well documented. Nevertheless, monitor concurrent use carefully and reduce dosage of sulphonylureas as necessary. Some patients may show a particularly exaggerated response. The manufacturers of other sulphonylureas often list chloramphenicol as an interacting drug,based on its interactions with tolbutamide and chlorpropamide, but direct information of an interaction does not appear to be available. No interaction would be expected with chloramphenicol eye drops, because systemic absorption is likely to be small.
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Brunová E,Slabochová Z, Platilová H, Pavlík F, Grafnetterová J, Dvoráček K. Interaction of tolbutamide and chloramphenicol in diabetic patients. Int J Clin Pharmacol Biopharm (1977) 15, 7–12.
Brunová E,Slabochová Z, Platilová H. Influencing the effect of Dirastan (tolbutamide). Simultaneous administration of chloramphenicol in patients with diabetes and bacterial urinary tractinflammation. Cas Lek Cesk (1974) 113, 72–5.
Ziegelasch H-J. Extreme hypoglykämie unter kombinierter behandlung mit tolbutamid,n-1butylbiguanidhydrochlorid und chloramphenikol. Z Gesamte Inn Med (1972) 27, 63–6.
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6. 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.