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‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
_______________17.10.2010________ ‫תאריך‬
‫שם תכשיר באנגלית ומספר הרישום‬
Avandia 4mg
Avandia 8mg
116-33-29800-22
116-34-29801-22
__GlaxoSmithKline (ISRAEL) Ltd. __‫שם בעל הרישום‬
‫השינויים בעלון מסומנים על רקע צהוב‬
‫לרופא‬
‫בעלון לרופא‬
‫בעלון‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
‫טקסט נוכחי‬
‫פרק בעלון‬
Myocardial Ischaemia
A retrospective analysis of data from 42 pooled shortterm clinical studies indicated that treatment with
rosiglitazone may be associated with an increased risk of
myocardial ischaemic events. However, in their entirety
the available data on the risk of cardiac ischaemia are
inconclusive (see Adverse Reactions Section). There are
limited clinical trial data in patients with ischaemic heart
disease and/or peripheral arterial disease. Therefore, as a
precaution, the use of rosiglitazone is not recommended
in these patients, particularly those with myocardial
ischaemic symptoms.
Myocardial Ischaemia
The available data indicate that treatment with
rosiglitazone may be associated with an
increased risk of myocardial ischaemic events
(see BOXED WARNING). There are limited
clinical trial data in patients with ischaemic
heart disease or peripheral arterial disease.
Threfore, as a precaution, the use of
rosiglitazone is not recommended in these
patients, particularly those with myocardial
ischaemic symptoms.
Warnings
and
Precautions
•
Bone health:
Long-term studies show an increased incidence of bone
fracture in patients, particularly female patients, taking
rosiglitazone (see Clinical Studies). The majority of the
fractures have occurred in the upper limbs and distal
lower limbs. In females, this increased incidence was
noted after the first year of treatment and persisted
during long-term treatment. The risk of fracture should
be considered in the care of patients, especially female
patients, treated with rosiglitazone.
•
Bone health:
In a 4 to 6 year study of glycaemic control
with monotherapy in recently diagnosed
patients with Type 2 diabetes mellitus, an
increased incidence of bone fracture was
noted in female patients taking rosiglitazone
(9.3%, 2.7 patients per 100 patient years) vs
metformin (5.1%, 1.5 patients per 100 patient
years) or glyburide/glibenclamide (3.5%, 1.3
patients per 100 patient years). The majority
of the fractures in the females who received
rosiglitazone were reported in the upper arm,
hand and foot. The risk of fracture should be
considered in the care of patients, especially
female patients, treated with rosiglitazone, and
attention should be given to assessing and
maintaining bone health according to current
standards of care.
congestive heart failure/pulmonary oedema
rosiglitazone + sulphonylurea vs. sulphonylurea common
rosiglitazone + metformin vs. sulphonylurea +
metformin - common
congestive heart failure/pulmonary oedema
rosiglitazone + sulphonylurea vs.
sulphonylurea - uncommon
events typically associated with cardiac ischaemia
events typically associated with cardiac
D:\308869790.doc
Adverse
Reactions
Cardiac
disorders
ischaemia
In a retrospective analysis of data from 42 pooled shortterm clinical studies, the overall incidence of events
typically associated with cardiac ischaemia was higher
for rosiglitazone containing regimens, 2.00 % versus
combined active and placebo comparators, 1.53 %
[hazard ratio (HR) 1.30 (95 % confidence interval
(CI) 1.004 - 1.69)]. This risk was increased when
rosiglitazone was added to established insulin and in
patients receiving nitrates for known ischaemic heart
disease. In an update to this retrospective analysis that
included 10 further studies that met the criteria for
inclusion, but were not available at the time of the
original analysis, the overall incidence of events
typically associated with cardiac ischaemia was not
statistically different for rosiglitazone containing
regimens, 2.21 % versus combined active and placebo
comparators, 2.08 % [HR 1.098 (95 % CI 0.809 1.354)]. In a prospective cardiovascular outcomes study
(mean follow-up 5.5 years) the primary endpoint events
of cardiovascular death or hospitalisation were similar
between rosiglitazone and active comparators [HR 0.99
(95 % CI 0.85 - 1.16)]. Two other long-term prospective
randomised controlled clinical trials (9,620 patients,
study duration >3 years in each study), comparing
rosiglitazone to some other approved oral antidiabetic
medicinal products or placebo, have not confirmed or
excluded the potential risk of cardiac ischaemia. In their
entirety, the available data on the risk of cardiac
ischaemia are inconclusive
In a retrospective analysis of data from 42
pooled short-term clinical studies, the overall
incidence of events typically associated with
cardiac ischaemia was higher for rosiglitazone
containing regimens, 2.00% versus combined
active and placebo comparators, 1.53%
[Hazard ratio 1.30 (95% confidence interval
1.004 - 1.69)]. This risk was increased when
rosiglitazone was added to established insulin
and in patients receiving nitrates for known
ischaemic heart disease.
bone fractures
bone fractures
rosiglitazone monotherapy vs. metformin; rosiglitazone
monotherapy vs. glyburide/glibenclamide – Common
rosiglitazone monotherapy vs. metformin;
rosiglitazone monotherapy vs.
glyburide/glibenclamide – Common
In a large observational study where patients
were well-matched at baseline, the incidence
of the composite endpoint myocardial
infarction and coronary revascularization was
17.46 events per 1000 person years for
rosiglitazone containing regimens and 17.57
events per 1000 person years for other antidiabetic agents [Hazard ratio 0.93 (95%
confidence interval 0.80 - 1.10)].
Three large long-term prospective randomised
controlled clinical trials (mean duration 41
months; 14,067 patients), comparing
rosiglitazone to some other approved oral
antidiabetic agents or placebo, have not
confirmed or excluded this risk. In their
entirety, the available data on the risk of
myocardial ischaemia are inconclusive.
rosiglitazone + metformin vs. sulphonylurea +
metformin - common
rosiglitazone + sulphonylurea vs. sulphonylurea –
common
The majority of the fractures in subjects who received
rosiglitazone were reported in the upper limbs and distal
lower limbs (See Warnings and Precautions)
D:\308869790.doc
The majority of the fractures in the females
who received rosiglitazone were reported in
the upper arm, hand and foot (See Warnings
and Precautions).
Adverse
Reactions
Musculoskeletal,
connective tissue
and bone
disorders