Medication Adverse Event Alert
February 21, 2007
| ISSUE: | Increased incidence of fractures among type 2 diabetic female patients on long-term rosiglitazone therapy |
| MEDICATIONS: | Avandia® (rosiglitazone maleate) |
| Avandamet® (rosiglitazone maleate and metformin hydrochloride) |
| Avandaryl® (rosiglitazone maleate and glimepiride) |
The following was posted on FDA Med Watch alert website dated February 20, 2007:
"Glaxo SmithKline (GSK) notified healthcare professionals of the results of a randomized, double-blind parallel group study [ADOPT] of 4,360 patients with recently diagnosed type 2 diabetes mellitus followed for 4-6 years to compare glycemic control with rosiglitazone relative to metformin and glyburide monotherapies. Significantly more female patients who received rosiglitazone experienced fractures of the upper arm, hand, or foot, than did female patients who received either metformin or glyburide. At GSK's request, an independent safety committee reviewed an interim analysis of fractures in another large; ongoing; controlled clinical trial and preliminary analysis was reported as being consistent with the observations from ADOPT. Healthcare professionals should consider the risk of fracture when initiating or treating female patients with type 2 diabetes mellitus with rosiglitazone."
An excerpt of GSK's "Dear Health Care Provider" letter is provided below:
"Recently, ADOPT (A Diabetes Outcome and Progression Trial) was completed. The results of ADOPT were published in the New England Journal of Medicine (Kahn et al., 2006. N Engl J Med, Vol. 355, No. 23:2427-2443). A review of the safety data in ADOPT was consistent, in general, with the known safety profile of rosiglitazone. However, significantly more female patients who received rosiglitazone experienced fractures than did female patients who received either metformin or glyburide). The observed incidence of fractures for male patients in ADOPT was similar among the three treatment groups (see table). Should you have any questions or require additional information, please contact your local GlaxoSmithKline information line (1-888-825-5249).
| Rosiglitazone | Metformin | Glyburide |
| MALE PATIENTS | 811 Males | 864 Males | 836 Males |
| 2957.6 PY | 2766.7 PY | 2612.8 PY |
| n (%) Rate/100 PY | n (%) Rate/100 PY | n (%) Rate/100 PY |
| Experienced a fracture | 32 (3.95)/ 1.16 | 29 (3.36)/ 0.98 | 28 (3.35)/ 1.07 |
| FEMALE PATIENTS | 645 Females | 590 Females | 605 Females |
| 2187.2 PY | 1948.0 PY | 1630.8 PY |
| n (%) Rate/100 PY | n (%) Rate/100 PY | n (%) Rate/100 PY |
| Experienced a fracture | 60 (9.30)/ 2.74 | 30 (5.09)/1.54 | 21 (3.47)/ 1.29 |
| Lower limb | 36 (5.58)/ 1.65 | 18 (3.05)/ 0.92 | 8 (1.32)/ 0.49 |
| Hip | 2 (0.31)/ 0.09 | 2 (0.34)/ 0.10 | 0/ 0 |
| Foot | 22 (3.41)/ 1.01 | 7 (1.19)/ 0.36 | 4 (0.66)/ 0.25 |
| Upper limb | 22 (3.41)/ 1.01 | 10 (1.70)/ 0.51 | 9 (1.49)/ 0.55 |
| Hand | 8 (1.24)/ 0.37 | 4 (0.68)/ 0.21 | 1 (0.17)/ 0.06 |
| Humerus | 5 (0.78)/ 0.23 | 0/ 0 | 0/ 0 |
| Spine | 1 (0.16)/ 0.05 | 1 (0.17)/ 0.05 | 1 (0.17)/ 0.06 |
| Other | 5 (0.78)/ 0.23 | 4 (0.68)/ 0.21 | 4 (0.66)/ 0.25 |
Rate/100 PY = Patients with Events per 100 Patient Years, n = number of patients
* Some patients experienced fractures in more than one category.
** Other sites of fracture included: ankle, femur, fibula, lower limb (general), patella, and tibia.
*** Other sites of fracture included: clavicle, forearm, radius, upper limb (general), and wrist.
