Drug interactions between Avandia and Lantus

rosiglitazone ↔ insulin glargine

Applies to:Avandia (rosiglitazone) and Lantus (insulin glargine)

ADJUST DOSE: Coadministration of a thiazolidinedione in combination with insulin may increase the risk of edema compared to insulin alone. The mechanism is unknown but may involve enhancement of the antinatriuretic and/or peripheral vasodilatory effects of insulin. In a retrospective study of 79 patients who were initially on a thiazolidinedione or insulin separately but were subsequently given both in combination, 20 patients (25.3%) developed edema during the combination, compared to 7 of 71 patients (9.9%) during insulin alone and 1 of 8 patients (12.5%) during thiazolidinedione alone. In a study of 319 type 2 diabetic patients inadequately controlled on twice-daily insulin monotherapy, edema occurred in 13.1% and 16.2% of the patients coadministered rosiglitazone 4 mg/day and 8 mg/day, respectively, compared to 4.7% of those coadministered a matching placebo. The specific combination of rosiglitazone and insulin has also been associated with an increased incidence of heart failure and other cardiovascular adverse events compared to insulin and placebo. Data are derived from three 26-week trials involving 876 patients with type 2 diabetes, including those with longstanding diabetes and a high prevalence of preexisting medical conditions (peripheral neuropathy, retinopathy, ischemic heart disease, vascular disease, and congestive heart failure). An increased incidence of edema, heart failure, and other adverse effects occurred in the patients receiving the combination compared to patients receiving insulin alone. In the studies, patients who experienced heart failure with the combination were on average older, had a longer duration of diabetes, and were mostly on the higher 8 mg daily dosage of rosiglitazone. However, 3 of 10 had no known prior evidence of any underlying cardiac condition. A subsequent study involving 220 type 2 diabetes patients with chronic renal failure found no difference in cardiovascular adverse events among patients receiving the combination and controls receiving insulin with placebo.

MANAGEMENT: When used with insulin, the manufacturer recommends that rosiglitazone dosage not exceed 4 mg/day and that patients be monitored for cardiovascular adverse effects. The combination should be discontinued if there is a lack of response (defined as a reduction in HbA1c or insulin dose after 4 to 5 months) or significant adverse effects occur. Patients should be advised to notify their physician immediately if they experience signs and symptoms of heart failure such as fluid retention, edema, rapid weight gain, or shortness of breath. Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations.