Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study.
BACKGROUND
A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 2005 to the Canadian market. The objective of our study was to quantify changes in AE rates and BMD scores, as well as associated alendronate discontinuation among patients before and after switch from brand to generic alendronate.


METHODS
A chart review of postmenopausal women 50 years of age and older between 2003 and 2007 was conducted in two specialized tertiary care referral centers. Patients on alendronate both before and after July 2005 were included. The change in the number of AEs, changes in BMD and associated alendronate discontinuation was compared before and after the switch from brand to generic alendronate.


RESULTS
301 women with an average age of 67.6 years (standard deviation (SD) = 9.5) had a total of 47 AEs between July 2003 and December 2007 that resulted in discontinuation of the medication. There was a significant increase in the rate of AEs per patient-months-at-risk from 0.0001 before to 0.0044 after October 2005 (p < 0.001). The most common AEs were GI in nature (stomach pain, GI upset, nausea, and reflux). In addition, 23 patients discontinued alendronate due to BMD reduction after January 2006. In these patients, BMD scores were significantly reduced from their prior BMD measures (change of -0.0534, p < 0.001 for spine BMD and change of -0.0338, p = 0.01 for femur BMD). Among patients who discontinued due to BMD reduction, BMD was stable in the period prior to January 2006 (change of -0.0066, p = 0.5 for spine BMD and change of 0.0011, p = 0.9 for femur BMD); however, testing for reduction after January 2006 in BMD measures (one-sided T-test) revealed there was a significant reduction in BMD scores for both anatomic sites (change of -0.0321, p = .005 for spine, change of -0.0205, p = 0.05 for femur).


CONCLUSIONS
Patients who were previously stable on doses of brand alendronate experienced an increase in AEs causing discontinuation after introduction of automatic substitution to generic alendronate. In addition, reductions in BMD were observed in some patients who had stable BMDs before January 2006. Given the substantial increase in AEs, generic alendronate may not be as well tolerated as brand alendronate.
Grima
Daniel T
DT
Center for Osteoporosis and Arthritis Research and Education (COARE), 1185 Rushbrooke Dr, Oakville, ON, L6 M 1H8, Canada.
Papaioannou
Alexandra
A
Airia
Parisa
P
Ioannidis
George
G
Adachi
Jonathan D
JD
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects* / Q000493:pharmacokinetics; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D016568:Drugs, Generic / Q000009:adverse effects*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010349:Patient Compliance / Q000706:statistics & numerical data; D011859:Radiography; D012189:Retrospective Studies; D012307:Risk Factors; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D013810:Therapeutic Equivalency
D050071:Bone Density Conservation Agents; D016568:Drugs, Generic; D019386:Alendronate
Ann Pharmacother. 2007 Jan;41(1):29-34
17190847
Mayo Clin Proc. 2002 Oct;77(10):1031-43
12374247
Ann Pharmacother. 2006 Jan;40(1):15-20
16303985
S Afr Med J. 2006 Aug;96(8):696-7
17019490
N Engl J Med. 1995 Nov 30;333(22):1437-43
7477143
BMC Health Serv Res. 2008 Jul 18;8:151
18638405
Osteoporos Int. 2008 Apr;19(4):581-7
17924051
Curr Med Res Opin. 2003;19(8):781-9
14687450
Osteoporos Int. 2009 Aug;20(8):1369-76
19020921
Clin Ther. 2008 May;30(5):834-44
18555931
Eur J Pharm Sci. 2007 Aug;31(5):262-70
17576054
Rheumatol Int. 2009 Dec;30(2):213-21
19430791
Clin Endocrinol (Oxf). 1986 Jan;24(1):57-62
3085989
Drug Saf. 1996 Mar;14(3):158-70
8934578
Curr Med Res Opin. 2009 Feb;25(2):449-52
19192989
BMC Musculoskelet Disord. 2004 Apr 06;5:11
15068488
Osteoporos Int. 2000;11(10):897-904
11199195
Lancet. 1996 Dec 7;348(9041):1535-41
8950879
Can Fam Physician. 1998 Feb;44:327-32
9512836
Semin Arthritis Rheum. 2006 Apr;35(5):293-305
16616152
JAMA. 1998 Dec 23-30;280(24):2077-82
9875874