Pioglitazone hydrochloride: In vivo drug-drug interaction studies have suggested that Pioglitazone may be weak inducer of CYP 450 isoform 3A4 substrate.
An enzyme inhibitor of CYP2C8 (such as gemfibrozil) may significantly increase the AUC of Pioglitazone and an enzyme inducer of CYP2C8 (such as rifampin) may significantly decrease the AUC of Pioglitazone. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with Pioglitazone, changes in diabetes treatment may be needed based on clinical response.
Glimepiride: A diminished hypoglycemic effect, possibly requiring an increased dose of Glimepiride, has been seen or might be expected on theoretical grounds with adrenaline (epinephrine), aminoglutethimide, chlorpromazine, corticosteroids, diazoxide, oral contraceptives, rifamycins and thiazides diuretics.
An increased hypoglycemic effect has occurred or might be expected with ACE inhibitors, alcohol, allopurinol, some analgesics (notably azapropazone, phenylbutazone and the salicylates), azole antifungals (fluconazole, ketoconazole and miconazole), chloramphenicol, cimetidine, clofibrate and related compounds, coumarin anticoagulants, halofenate, heparin, MAOIs, octreotide (although this may also produce hyperglycemia), ranitidine, sulfinpyrazone, sulfonamides (including co-trimoxazole), tetracyclines, tricyclic antidepressants and thyroid hormones.
Beta blockers have been reported both to increase hypoglycemia and to mask typical sympathetic warning signs. There are sporadic and conflicting reports of a possible interaction with calcium channel blocker, but overall any effect seems to be of little clinical significance.
In addition to producing hypoglycemia alcohol can interact with chlorpropamide to produce an unpleasant flushing reaction. Such an effect is rare with other sulfonylureas and alcohol.