4. CLINICAL PARTICULARS
4.8 Undesirable effects
Additions in bold text
In osteoporosis treatment and prevention studies involving over 13,000 postmenopausal women, all undesirable reactions were recorded. The duration of treatment in these studies ranged from 6 to 60 months. The majority of undesirable reactions have not usually required cessation of therapy.
The undesirable reactions associated with the use of raloxifene in osteoporosis clinical trials are summarised in the table below.
The following statement added above the clinical trial and post-marketing adverse event tables and as such the frequency classifications of adverse events deleted from within the tables.
The following convention has been used for the classification of the adverse reactions: very common ( ³1/10), common ( ³1/100 to <1/10), uncommon ( ³1/1,000 to <1/100), rare ( ³1/10,000 to <1/1,000), very rare ( <1/10,000), not known (cannot be estimated from the available data).
Added following paragraph
In a study of 10,101 postmenopausal women with documented coronary heart disease or at increased risk for coronary events (RUTH), the occurrence of vasodilatation (hot flushes) was 7.8% in the raloxifene-treated patients and 4.7% in the placebo-treated patients.
Changes to the following paragraph, shown in bold text
Across all placebo-controlled clinical trials of raloxifene in osteoporosis, venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis, occurred at a frequency of approximately 0.8% or 3.22 cases per 1,000 patient years.
Added following paragraphs
In the RUTH study, venous thromboembolic events occurred at a frequency of approximately 2.0% or 3.88 cases per 1,000 patient-years in the raloxifene group and 1.4% or 2.70 cases per 1,000 patient-years in the placebo group. The hazard ratio for all VTE events in the RUTH study was HR = 1.44, (1.06 – 1.95). Superficial vein thrombophlebitis occurred at a frequency of 1% in the raloxifene group and 0.6% in the placebo group.
In the RUTH study, leg cramps were observed in 12.1% of raloxifene-treated patients and 8.3% of placebo-treated patients.
Changes shown in bold text
One further change was seen which was not statistically significant (P >0.05), but which did show a significant dose trend. This was peripheral oedema, which occurred in the prevention population at an incidence of 3.1% for Evista and 1.9% for placebo; and in the treatment population occurred at an incidence of 7.1% for Evista and 6.1% for placebo. In the RUTH study, peripheral oedema occurred in 14.1% of the raloxifene-treated patients and 11.7% of the placebo-treated patients, which was statistically significant.
Slightly decreased (6-10%) platelet counts have been reported during raloxifene treatment in placebo-controlled clinical trials of raloxifene in osteoporosis.
Added following paragraph
In a study (RUTH) of postmenopausal women with documented coronary heart disease or at increased risk for coronary events, an additional adverse reaction of cholelithiasis occurred in 3.3% of patients treated with raloxifene and 2.6% of patients treated with placebo. Cholecystectomy rates for raloxifene (2.3%) were not statistically significantly different from placebo (2.0%).
Deletions shown in strikethrough text and changes in bold text
The following events have been reported in post-marketing experience are presented in the table below.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
a) Skeletal effects
Deletions shown in strikethrough text and additions in bold text
Evista reduced the new vertebral fracture risk by 39% (RR 0.61; CI 0.43, 0.88). An effect on non-vertebral fractures has not been demonstrated. During From the 4th to the 8th year, patients were permitted the concomitant use of bisphosphonates, calcitonin, and fluorides. An effect on extravertebral fractures has not been demonstrated and all patients in this study received calcium and vitamin D supplementation.
In the RUTH study overall clinical fractures were collected as a secondary endpoint. Evista reduced the incidence of clinical vertebral fractures by 35% compared with placebo (HR 0.65, CI 0.47, 0.89). These results may have been confounded by baseline differences in BMD and vertebral fractures. There was no difference between treatment groups in the incidence of new non-vertebral fractures. During the whole length of the study, concomitant use of other bone-active medications was permitted.
A similar increase in BMD was seen in the treatment population who received Evista for up to 7 years.
b) Effects on lipid metabolism and cardiovascular risk
Additions in bold text
Evista therapy for 8 years did not significantly affect the risk of cardiovascular events in patients enrolled in the osteoporosis treatment study. Similarly, in the RUTH study, raloxifene did not affect the incidence of myocardial infarction, hospitalised acute coronary syndrome, stroke or overall mortality, including overall cardiovascular mortality, compared to placebo (for the increase in risk of fatal stroke, see section 4.4).
d) Effects on breast tissue
Deleted
The effect of Evista on breast cancer beyond 4 years is unknown.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Deletions shown in strikethrough text
Date of first authorisation: 5 August 1998
Date of last renewal of the authorisation: 28 July 2003
10. DATE OF REVISION OF THE TEXT
New date:
27 March 2007
|
