Drug Interaction Report

ADJUST DOSE: Coadministration with gemfibrozil may significantly increase the plasma concentrations of rosiglitazone. The proposed mechanism is gemfibrozil inhibition of the CYP450 2C8-mediated metabolism of rosiglitazone. In 10 healthy volunteers given gemfibrozil 600 mg twice daily for two days prior to coadministration with a single 4 mg dose of rosiglitazone on day 3, mean rosiglitazone systemic exposure (AUC) increased by 127% and elimination half-life from 3.6 to 7.6 hours, while the plasma rosiglitazone concentration measured 24 hours after dosing increased by 9.8-fold.

MANAGEMENT: Given the potential for dose-related adverse events, a lower dosage of rosiglitazone may be necessary when used with gemfibrozil, particularly in patients already receiving a higher dosage of rosiglitazone (e.g., 8 mg/day). Close monitoring for the development of hypoglycemia and other adverse effects is recommended, such as fluid retention; weight gain; new or worsening heart failure; pulmonary, peripheral, and macular edema; angina; bone fractures; anemia; and liver enzyme elevations. Patients should regularly monitor their blood sugar and learn how to recognize and treat hypoglycemia, which may include symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, and palpitation. Likewise, patients should be observed for potential loss of glycemic control following discontinuation of gemfibrozil, and the rosiglitazone dosage adjusted as necessary.

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.