Sulfonylureas drug interactions

Bussing R, Gende A. Severe hypoglycemia from clarithromycin-sulfonylurea drug interaction. Diabetes Care 2002 25(9) 1659-61. 

Significant drug-drug interactions are those that potentiate the effects of other agents and require dosage modification. These include certain anticoagulants, hypoglycemic sulfonylureas, and hydantoin anticonvulsants. 

The first-generation sulfonylureas are not frequently used in the modem management of diabetes mellitus because of their relatively low specificity of action, delay in time of onset, occasional long duration of action, and a variety of side effects. They also tend to have more adverse drug interactions than the second-generation sulfonylureas. They are occasionally used in patients who have achieved previous adequate control with these agents. 

Adverse effect Hypoglycemia due to sulfonylureas Dose-relation toxic effect Time-course time-independent Susceptibility factors disease (impaired liver or kidney function, alcoholism) drug interactions reduced food intake exercise... 

Drug interactions metabolized by CYP450 3A4, may interact with drugs that inhibit or induce this enzyme May cause hypoglycemia in patients receiving insulin, sulfonylureas, or metformin contraindicated in pregnant women Limit vitamin A supplements... 

Associated with renal dysfunction (4 PGs) and hypoglycemia. Many drug interactions (ethanol T GI bleeding, T effects of sulfonylurea hypoglycemics, and warfarin, 4 effects of uricosurics). 

Cimetidine 300mg po tid 800 mg po bid 60% 100% 75% 25% Multiple drug-drug interactions beta blockers, sulfonylurea, theophylline, warfarin, etc... 

Drug interactions with sulfonylureas and biguanides are common non-steroidal antiinflammatory drugs, warfarin, alcohol, monoamine oxidase inhibitors, some uricosurics, some antibacterials and some antifungals can interact with them. All increase the risk of hypoglycaemia. The mechanism is probably competition for metabolizing enzymes or displacement from plasma protein binding sites. 

Fluconazole inhibits CYP3A4 and CYP2C9 and thus significantly increases plasma concentrations of amprenavir, cisapride, cyclosporine, phenytoin, sulfonylureas, tacrolimus, theophylline, telithromycin, and warfarin. Patients receiving >400 mg daily or azotemic patients may experience additional drug interactions. Rifampin decreases the fluconazole AUC by -25%. 

A. Sulfonylureas. Toxicity depends on the agent and the total amount ingested. Toxicity may also occur owing to drug interactions, resulting in impaired elimination of the oral agent. 

Drug/Food interactions Absorption of glipizide is delayed by approximately 40 minutes when taken with food the drug is more effective when given approximately 30 minutes before a meal. The other sulfonylureas may be taken with food. 

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