Medication Adverse Event Alert
March 9, 2007
| ISSUE: | Increased incidence of fractures among female type-2 diabetic patients on long-term pioglitazone therapy* *(see also RxAmerica, LLC, Medication Event Alert on rosiglitazone and increased incidence fractures in female patients dated 2/20/2007) |
| MEDICATION: | Actos® (pioglitazone) tablets ACTOplus met® (pioglitazone and metformin hydrochloride) tablets Duetact® (pioglitazone and glimepiride) tablets |
The following was posted on FDA Med Watch alert website dated March 9, 2007:
"Takeda and FDA notified healthcare professionals of recent safety data concerning pioglitazone-containing products. The results of an analysis of the manufacturer's clinical trial database of pioglitazone showed more reports of fractures in female patients taking pioglitazone than those taking a comparator (either placebo or active). The majority of fractures observed in female patients were in the distal upper limb (forearm, hand and wrist) or distal lower limb (foot, ankle, fibula and tibia). There were more than 8100 patients in the pioglitazone-treated groups and over 7400 patients in the comparator-treated groups. The duration of pioglitazone treatment was up to 3.5 years. Healthcare professionals should consider the risk of fracture when initiating or treating female patients with type 2 diabetes mellitus with pioglitazone-containing products."
An excerpt of Takeda's "Dear Health Care Provider" letter dated March 2007 is provided below:
"As part of our ongoing evaluation of all safety information, Takeda has recently undertaken an analysis of its clinical trial database of pioglitazone with a special focus on fractures, comparing patients treated with pioglitazone or a comparator (either placebo or active). The maximum duration of pioglitazone treatment was up to 3.5 years. There were more than 8100 patients in the pioglitazone-treated groups and over 7400 patients in the comparator-treated groups, corresponding to just under 12,000 patient-years exposure per group. There was no increased risk of fracture identified in men. However, there were more reports of fractures in female patients taking pioglitazone than those taking a comparator.
The majority of fractures observed in female patients who received pioglitazone were in the distal upper limb (forearm, hand and wrist) or distal lower limb (foot, ankle, fibula and tibia). The fracture incidence calculated was 1.9 fractures per 1 00 patient-years in the pioglitazone-treated group and 1. 1 fractures per 100 patient-years in the comparator-treated group. The observed excess risk of fractures for women in this data set on pioglitazone is therefore 0.8 fractures per 100 patient-years of use. The explanation for this finding is currently not known. It should also be noted that none of the pioglitazone studies in the database addressed, or were designed to study, the effect on bone, but fractures were collected as adverse events. Due to the limitations of the existing data set, multiple known risk factors for fractures cannot be excluded as confounding variables. Further evaluation of these findings is ongoing.
The risk of fracture should be considered in the care of female patients with type 2 diabetes mellitus who are currently being treated with pioglitazone, or when initiation of pioglitazone treatment is being considered.
Should you have any questions or require additional information, please contact Takeda Pharmaceuticals North America, Inc., information line at 1-877-TAKEDA7."
