PHILADELPHIA and LONDON, May 30 /PRNewswire-FirstCall/ --
GlaxoSmithKline (NYSE: GSK) today confirms that a letter to the editor
summarizing additional Avandia cardiovascular safety data from several
large-scale clinical trials was published online today in The Lancet. This
letter, written by Ronald L. Krall, MD, Chief Medical Officer of
GlaxoSmithKline, provides the necessary context and clarifies the safety
record of Avandia, which is based on sound science and backed by one of the
largest research programs ever in diabetes.
Key data points include:
-- The recent meta-analysis published in New England Journal of Medicine,
which has been widely cited in media reports, omitted the total
percentage number of events. The actual number of heart attacks
represents a very low frequency of events - 0.6% for both Avandia and
the control group (Avandia 86/14,371; control 72/11,634).
-- Further analyses from ADOPT and DREAM - two long-term prospective
clinical trials - show that the incidence of ischemic cardiovascular
events with Avandia is comparable to the two gold standard medicines
used to treat type 2 diabetes (metformin or a sulfonylurea) in the
ADOPT study, and to placebo in the DREAM study.
-- Findings from a soon-to-be-published study, using a managed care
database of more than 30,000 diabetes patients in a real-world setting,
show the incidence of hospitalizations for heart attack, and/or for a
surgery known as revascularization for patients on Avandia is the same
as for other diabetes treatments.
-- The independent safety monitoring board for the RECORD trial - a large,
long-term clinical trial, which has been designed to look at
cardiovascular outcomes in people with diabetes - reviewed an interim
analysis of cardiovascular endpoints in all study participants, and
determined that the study should be allowed to continue.
To summarize, data from long-term, large-scale, prospective clinical
trials show that the overall ischemic cardiovascular safety profile,
including cardiovascular death, among diabetes patients treated with
Avandia is comparable to patients treated with two other widely used
diabetes medicines. Avandia is an effective medicine that is an important
treatment for millions of patients who are using it to manage their
diabetes, a disease with potentially devastating consequences if left
unmanaged.
Diabetes is at epidemic proportions, and GlaxoSmithKline believes that
a balanced and responsible approach to assessing the risks and benefits of
all available treatments is in the best interests of patients and everyone
with a stake in treating this disease successfully.
UK Media inquiries: Phil Thomson (020) 8047 5502
Joss Mathieson (020) 8047 5502
Gwenan White (020) 8047 5502
US Media inquiries: Nancy Pekarek (215) 751 7709
Mary Anne Rhyne (919) 483 2839
Alice Hunt (215) 751 7709
US Analyst/ Investor inquiries: Frank Murdolo (215) 751 7002
Tom Curry (215) 751 5419
European Analyst/Investor inquiries: Anita Kidgell (020) 8047 5542
David Mawdsley (020) 8047 5564
Sally Ferguson (020) 8047 5543
[Avandia is indicated as an adjunct to diet and exercise to improve
glycemic control in patients with type 2 diabetes. Avandia is indicated as
monotherapy and in combination with a sulfonylurea, metformin, or insulin
when diet, exercise, and a single agent do not result in adequate glycemic
control. Avandia is also indicated for use in combination with a
sulfonylurea plus metformin when diet, exercise, and both agents do not
result in adequate glycemic control.
Avandamet is indicated as an adjunct to diet and exercise to improve
glycemic control in patients with type 2 diabetes mellitus when treatment
with dual rosiglitazone and metformin therapy is appropriate.
Avandaryl is indicated as an adjunct to diet and exercise to improve
glycemic control in patients with type 2 diabetes mellitus when treatment
with dual rosiglitazone and glimepiride therapy is appropriate.
Important Clinical Considerations When Prescribing AVANDIA(R)
(rosiglitazone maleate), AVANDAMET(R) (rosiglitazone maleate/metformin HCl)
or AVANDARYL(TM) (rosiglitazone maleate and glimepiride)
CONTRAINDICATIONS FOR AVANDAMET:
-- Renal disease or renal dysfunction (based on serum creatinine levels
Greater Than or Equal To 1.5 mg/dL in males, Greater Than or Equal To
1.4 mg/dL in females)
Avandamet should not be initiated in patients Greater Than or Equal 80
years of age unless creatinine clearance is normal. Temporarily discontinue
Avandamet at the time of or prior to procedures involving intravascular
iodinated contrast materials. Withhold Avandamet for 48 hours post
procedure and reinstitute only after normal renal function has been
established.
-- Acute or chronic metabolic acidosis, including diabetic ketoacidosis
Withhold therapy in the presence of any condition associated with
hypoxemia, dehydration, or sepsis.
Black Box WARNING for AVANDAMET: LACTIC ACIDOSIS
Lactic acidosis is a rare but serious metabolic complication that can
occur due to metformin accumulation during therapy with Avandamet
The reported incidence of lactic acidosis in patients receiving
metformin hydrochloride is approximately 0.03 cases/1000 patient-years and
may be fatal in approximately 50% of cases. Reported cases have occurred
primarily in diabetic patients with significant renal insufficiency. The
risk of lactic acidosis increases with the degree of renal dysfunction and
the patient's age. This risk may be significantly decreased by regular
monitoring of renal function in patients taking Avandamet and by use of the
minimum effective dose. Patients with congestive heart failure requiring
pharmacologic management are also at increased risk of lactic acidosis.
The onset of lactic acidosis often is subtle and accompanied only by
nonspecific symptoms such as malaise, myalgias, respiratory distress,
increasing somnolence, and nonspecific abdominal distress.
Patients should be cautioned against excessive alcohol intake when
taking Avandamet. Avandamet should be temporarily discontinued prior to
surgical procedures, specifically those involving restricted intake of food
and fluids.
CONTRAINDICATIONS FOR AVANDARYL:
-- Diabetic ketoacidosis, with or without coma. This condition should be
treated with insulin
CARDIAC CONSIDERATIONS:
-- Rosiglitazone, like other thiazolidinediones, is associated with fluid
retention (which can lead to or exacerbate heart failure) and edema
-- All patients, particularly those receiving concurrent sulfonylurea or
insulin therapy, those at risk for heart failure, and those with mild
to moderate heart failure (New York Heart Association [NYHA] Class 1
and 2), should be monitored for signs and symptoms relating to fluid
retention, including heart failure
-- In addition, a higher incidence of other cardiovascular events was
observed when rosiglitazone was added to insulin or when used in
patients with pre-existing mild to moderate heart failure
-- Avandamet and Avandaryl are not indicated for use in combination with
insulin
-- Avandia, Avandamet, and Avandaryl are not recommended in patients with
NYHA Class 3 and 4 cardiac status
ADDITIONAL CARDIAC CONSIDERATIONS FOR AVANDARYL:
-- The UGDP trial found that tolbutamide, a sulfonylurea, was associated
with increased risk of cardiovascular mortality. Glimepiride was not
studied in this trial; however, it is prudent to consider that this
warning may apply to all sulfonylureas
OTHER CONSIDERATIONS:
HEPATIC:
-- Check liver enzymes prior to initiation of Avandia, Avandamet, or
Avandaryl and periodically per clinical judgment
-- Avandia, Avandamet, and Avandaryl should not be started in patients
with active liver disease or with ALT levels >2.5X the
upper limit of normal
-- Postmarketing reports of hepatitis and ALT >3X the upper limit of
normal have been received for rosiglitazone. Very rarely, these reports
have involved hepatic failure with and without fatal outcome, although
causality has not been established
ADDITIONAL HEPATIC CONSIDERATIONS FOR AVANDAMET:
-- Since impaired hepatic function has been associated with some cases of
lactic acidosis, Avandamet should generally be avoided in patients with
clinical or laboratory evidence of hepatic disease
GENERAL:
-- Postmarketing reports of new onset or worsening macular edema have been
received for patients taking rosiglitazone or another
thiazolidinedione. In some cases, patients' symptoms improved following
discontinuation of their thiazolidinedione
-- An increased incidence of bone fracture has been observed in women
taking rosiglitazone. The majority of the fractures were reported in
the upper arm (humerus), hand, and foot
-- Anemia, hypoglycemia, resumption of ovulation, and weight gain
ADDITIONAL CONSIDERATIONS FOR AVANDARYL:
-- As with all sulfonylureas, severe hypoglycemia may occur. Elderly,
debilitated, or malnourished patients, or patients with adrenal,
pituitary, renal, or hepatic insufficiency may be more sensitive to the
glucose-lowering effect of sulfonylureas and should be started on
Avandaryl 4 mg/1 mg. If hypoglycemia occurs, a reduction in the dose of
the sulfonylurea component may be necessary.]
SOURCE GlaxoSmithKline
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CONTACT:
UK Media, Phil Thomson, +020-8047-5502, or
Joss Mathieson, +020-8047-5502, or Gwenan White, +020-8047-5502,
or US Media, Nancy Pekarek, +1-215-751-7709, or Mary Anne Rhyne,
+1-919-483-2839, or Alice Hunt, +1-215-751-7709, or US Analysts
and Investors, Frank Murdolo, +1-215-751-7002, or Tom Curry,
+1-215-751 5419, or European Analysts and Investors, Anita
Kidgell, +020-8047-5542, or David Mawdsley, +020-8047-5564, or
Sally Ferguson, +020-8047-5543, all of GlaxoSmithKline
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