Avandia Information
Avandia (Rosiglitazone)
Avandia (Rosiglitazone) Indications And Usage
Avandia (Rosiglitazone) is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes mellitus.
Avandia (Rosiglitazone) Dosage And Administration
The management of antidiabetic therapy should be individualized.
All patients should start Avandia (Rosiglitazone) at the lowest recommended dose. Further
increases in the dose of Avandia (Rosiglitazone) should be accompanied by careful monitoring for
adverse events related to fluid retention .
Avandia (Rosiglitazone) may be administered at a starting dose of 4 mg either as a single
daily dose or in 2 divided doses. For patients who respond inadequately
following 8 to 12 weeks of treatment, as determined by reduction in fasting
plasma glucose (FPG), the dose may be increased to 8 mg daily as monotherapy or
in combination with metformin, sulfonylurea, or sulfonylurea plus metformin.
Reductions in glycemic parameters by dose and regimen are described under . Avandia (Rosiglitazone) may be taken with or
without food.
The total daily dose of Avandia (Rosiglitazone) should not exceed 8 mg.
The usual starting dose of Avandia (Rosiglitazone) is 4 mg administered either as
a single dose once daily or in divided doses twice daily. In clinical trials,
the 4-mg twice-daily regimen resulted in the greatest reduction in FPG and
hemoglobin A1c (HbA1c).
When Avandia (Rosiglitazone) is added to existing therapy, the current dose(s) of
the agent(s) can be continued upon initiation of therapy with Avandia (Rosiglitazone) .
When used in combination with sulfonylurea, the usual starting dose of
Avandia (Rosiglitazone) is 4 mg administered as either a single dose once daily or in divided
doses twice daily. If patients report hypoglycemia, the dose of the sulfonylurea
should be decreased.
The usual starting dose of Avandia (Rosiglitazone) in combination with metformin is 4 mg
administered as either a single dose once daily or in divided doses twice daily.
It is unlikely that the dose of metformin will require adjustment due to
hypoglycemia during combination therapy with Avandia (Rosiglitazone) .
The usual starting dose of Avandia (Rosiglitazone) in combination with a
sulfonylurea plus metformin is 4 mg administered as either a single dose once
daily or divided doses twice daily. If patients report hypoglycemia, the dose of
the sulfonylurea should be decreased.
No dosage adjustment is necessary when Avandia (Rosiglitazone) is used as monotherapy in
patients with renal impairment. Since metformin is contraindicated in such
patients, concomitant administration of metformin and Avandia (Rosiglitazone) is also
contraindicated in patients with renal impairment.
Liver enzymes should be measured prior to initiating treatment with Avandia (Rosiglitazone) .
Therapy with Avandia (Rosiglitazone) should not be initiated if the patient exhibits clinical
evidence of active liver disease or increased serum transaminase levels (ALT
>2.5X upper limit of normal at start of therapy). After initiation of
Avandia (Rosiglitazone) , liver enzymes should be monitored periodically per the clinical
judgment of the healthcare professional.
Data are insufficient to recommend pediatric use of Avandia (Rosiglitazone) .
Avandia (Rosiglitazone) Dosage Forms And Strengths
Pentagonal film-coated TILTAB tablet
contains rosiglitazone as the maleate as follows:
Avandia (Rosiglitazone) Contraindications
Initiation of Avandia (Rosiglitazone) in patients with established New York Heart Association
(NYHA) Class III or IV heart failure is contraindicated .
Avandia (Rosiglitazone) Warnings And Precautions
Avandia (Rosiglitazone) , like other thiazolidinediones, alone or in combination
with other antidiabetic agents, can cause fluid retention, which may exacerbate
or lead to heart failure. Patients should be observed for signs and symptoms of
heart failure. If these signs and symptoms develop, the heart failure should be
managed according to current standards of care. Furthermore, discontinuation or
dose reduction of rosiglitazone must be considered .
Patients with congestive heart failure (CHF) NYHA Class I and II treated with
Avandia (Rosiglitazone) have an increased risk of cardiovascular events. A 52-week,
double-blind, placebo-controlled echocardiographic study was conducted in 224
patients with type 2 diabetes mellitus and NYHA Class I or II CHF (ejection
fraction ≤45%) on background antidiabetic and CHF therapy. An independent
committee conducted a blinded evaluation of fluid-related events (including
congestive heart failure) and cardiovascular hospitalizations according to
predefined criteria (adjudication). Separate from the adjudication, other
cardiovascular adverse events were reported by investigators. Although no
treatment difference in change from baseline of ejection fractions was observed,
more cardiovascular adverse events were observed following treatment with
Avandia (Rosiglitazone) compared to placebo during the 52-week study. (See Table 1.)
Initiation of Avandia (Rosiglitazone) in patients with established NYHA Class III or IV heart
failure is contraindicated. Avandia (Rosiglitazone) is not recommended in patients with
symptomatic heart failure.
Patients experiencing acute coronary syndromes have not been studied in
controlled clinical trials. In view of the potential for development of heart
failure in patients having an acute coronary event, initiation of Avandia (Rosiglitazone) is not
recommended for patients experiencing an acute coronary event, and
discontinuation of Avandia (Rosiglitazone) during this acute phase should be considered.
Patients with NYHA Class III and IV cardiac status (with or without CHF) have
not been studied in controlled clinical trials. Avandia (Rosiglitazone) is not recommended in
patients with NYHA Class III and IV cardiac status.
A meta-analysis was conducted retrospectively to assess cardiovascular
adverse events reported across 42 double-blind, randomized, controlled clinical
trials (mean duration 6 months). These studies had been
conducted to assess glucose-lowering efficacy in type 2 diabetes, and
prospectively planned adjudication of cardiovascular events had not occurred in
the trials. Some trials were placebo-controlled and some used active oral
antidiabetic drugs as controls. Placebo-controlled studies included monotherapy
trials (monotherapy with Avandia (Rosiglitazone) versus placebo monotherapy) and add-on trials
(Avandia (Rosiglitazone) or placebo, added to sulfonylurea, metformin, or insulin). Active
control studies included monotherapy trials (monotherapy with Avandia (Rosiglitazone) versus
sulfonylurea or metformin monotherapy) and add-on trials (Avandia (Rosiglitazone) plus
sulfonylurea or Avandia (Rosiglitazone) plus metformin, versus sulfonylurea plus metformin). A
total of 14,237 patients were included (8,604 in treatment groups containing
Avandia (Rosiglitazone) , 5,633 in comparator groups), with 4,143 patient-years of exposure to
Avandia (Rosiglitazone) and 2,675 patient-years of exposure to comparator. Myocardial ischemic
events included angina pectoris, angina pectoris aggravated, unstable angina,
cardiac arrest, chest pain, coronary artery occlusion, dyspnea, myocardial
infarction, coronary thrombosis, myocardial ischemia, coronary artery disease,
and coronary artery disorder. In this analysis, an increased risk of myocardial
ischemia with Avandia (Rosiglitazone) versus pooled comparators was observed (2% Avandia (Rosiglitazone) versus
1.5% comparators, odds ratio 1.4, 95% confidence interval [CI] 1.1, 1.8). An
increased risk of myocardial ischemic events with Avandia (Rosiglitazone) was observed in the
placebo-controlled studies, but not in the active-controlled studies. (See
Figure 1.)
A greater increased risk of myocardial ischemic events was observed in
studies where Avandia (Rosiglitazone) was added to insulin (2.8% for Avandia (Rosiglitazone) plus insulin versus
1.4% for placebo plus insulin, [OR 2.1, 95% CI 0.9, 5.1]). This increased risk
reflects a difference of 3 events per 100 patient-years (95% CI -0.1, 6.3)
between treatment groups.
Figure 1. Forest Plot of Odds Ratios (95% Confidence
Intervals) for Myocardial Ischemic Events in the Meta-Analysis of 42 Clinical
Trials
A greater increased risk of myocardial ischemia was also observed in patients
who received Avandia (Rosiglitazone) and background nitrate therapy. For Avandia (Rosiglitazone) (N = 361)
versus control (N = 244) in nitrate users, the odds ratio was 2.9 (95% CI 1.4,
5.9), while for non-nitrate users (about 14,000 patients total), the odds ratio
was 1.3 (95% CI 0.9, 1.7). This increased risk represents a difference of 12
myocardial ischemic events per 100 patient-years (95% CI 3.3, 21.4). Most of the
nitrate users had established coronary heart disease. Among patients with known
coronary heart disease who were not on nitrate therapy, an increased risk of
myocardial ischemic events for Avandia (Rosiglitazone) versus comparator was not demonstrated.
Avandia (Rosiglitazone)
Avandia (Rosiglitazone) Adverse Reactions
In clinical trials, approximately 9,900 patients with type 2 diabetes have
been treated with Avandia (Rosiglitazone) .
The incidence and types of adverse events reported in short-term clinical
trials of Avandia (Rosiglitazone) as monotherapy are shown in Table 4.
Overall, the types of adverse reactions without regard to causality reported
when Avandia (Rosiglitazone) was used in combination with a sulfonylurea or metformin were
similar to those during monotherapy with Avandia (Rosiglitazone) .
Events of anemia and edema tended to be reported more frequently at higher
doses, and were generally mild to moderate in severity and usually did not
require discontinuation of treatment with Avandia (Rosiglitazone) .
In double-blind studies, anemia was reported in 1.9% of patients receiving
Avandia (Rosiglitazone) as monotherapy compared to 0.7% on placebo, 0.6% on sulfonylureas, and
2.2% on metformin. Reports of anemia were greater in patients treated with a
combination of Avandia (Rosiglitazone) and metformin (7.1%) and with a combination of Avandia (Rosiglitazone)
and a sulfonylurea plus metformin (6.7%) compared to monotherapy with Avandia (Rosiglitazone) or
in combination with a sulfonylurea (2.3%). Lower pre-treatment
hemoglobin/hematocrit levels in patients enrolled in the metformin combination
clinical trials may have contributed to the higher reporting rate of anemia in
these studies .
In clinical trials, edema was reported in 4.8% of patients receiving Avandia (Rosiglitazone)
as monotherapy compared to 1.3% on placebo, 1.0% on sulfonylureas, and 2.2% on
metformin. The reporting rate of edema was higher for Avandia (Rosiglitazone) 8 mg in
sulfonylurea combinations (12.4%) compared to other combinations, with the
exception of insulin. Edema was reported in 14.7% of patients receiving Avandia (Rosiglitazone)
in the insulin combination trials compared to 5.4% on insulin alone. Reports of
new onset or exacerbation of congestive heart failure occurred at rates of 1%
for insulin alone, and 2% (4 mg) and 3% (8 mg) for insulin in combination with
Avandia (Rosiglitazone) .
In controlled combination therapy studies with sulfonylureas, mild to
moderate hypoglycemic symptoms, which appear to be dose related, were reported.
Few patients were withdrawn for hypoglycemia (less than 1%) and few episodes of
hypoglycemia were considered to be severe (less than 1%). Hypoglycemia was the most
frequently reported adverse event in the fixed-dose insulin combination trials,
although few patients withdrew for hypoglycemia (4 of 408 for Avandia (Rosiglitazone) plus
insulin and 1 of 203 for insulin alone). Rates of hypoglycemia, confirmed by
capillary blood glucose concentration less than or equal to 50 mg/dL, were 6% for insulin alone and
12% (4 mg) and 14% (8 mg) for insulin in combination with Avandia (Rosiglitazone) .
A 4- to 6-year study (ADOPT) compared the use of Avandia (Rosiglitazone) (n = 1,456),
glyburide (n = 1,441), and metformin (n = 1,454) as monotherapy in patients
recently diagnosed with type 2 diabetes who were not previously treated with
antidiabetic medication. Table 5 presents adverse reactions without regard to
causality; rates are expressed per 100 patient-years (PY) exposure to account
for the differences in exposure to study medication across the 3 treatment
groups.
In ADOPT, fractures were reported in a greater number of women treated with
Avandia (Rosiglitazone) (9.3%, 2.7/100 patient-years) compared to glyburide (3.5%, 1.3/100
patient-years) or metformin (5.1%, 1.5/100 patient-years). The majority of the
fractures in the women who received rosiglitazone were reported in the upper
arm, hand, and foot. The observed incidence of fractures for male patients was similar
among the 3 treatment groups.
Avandia (Rosiglitazone) has been evaluated for safety in a single, active-controlled trial of
pediatric patients with type 2 diabetes in which 99 were treated with Avandia (Rosiglitazone)
and 101 were treated with metformin. The most common adverse reactions (greater than 10%)
without regard to causality for either Avandia (Rosiglitazone) or metformin were headache (17%
versus 14%), nausea (4% versus 11%), nasopharyngitis (3% versus 12%), and
diarrhea (1% versus 13%). In this study, one case of diabetic ketoacidosis was
reported in the metformin group. In addition, there were 3 patients in the
rosiglitazone group who had FPG of ∼300 mg/dL, 2+ ketonuria, and an elevated
anion gap.
Decreases in mean hemoglobin and hematocrit occurred in a dose-related
fashion in adult patients treated with Avandia (Rosiglitazone) (mean decreases in individual
studies as much as 1.0 g/dL hemoglobin and as much as 3.3% hematocrit). The
changes occurred primarily during the first 3 months following initiation of
therapy with Avandia (Rosiglitazone) or following a dose increase in Avandia (Rosiglitazone) . The time course
and magnitude of decreases were similar in patients treated with a combination
of Avandia (Rosiglitazone) and other hypoglycemic agents or monotherapy with Avandia (Rosiglitazone) .
Pre-treatment levels of hemoglobin and hematocrit were lower in patients in
metformin combination studies and may have contributed to the higher reporting
rate of anemia. In a single study in pediatric patients, decreases in hemoglobin
and hematocrit (mean decreases of 0.29 g/dL and 0.95%, respectively) were
reported. Small decreases in hemoglobin and hematocrit have also been reported
in pediatric patients treated with Avandia (Rosiglitazone) . White blood cell counts also
decreased slightly in adult patients treated with Avandia (Rosiglitazone) . Decreases in
hematologic parameters may be related to increased plasma volume observed with
treatment with Avandia (Rosiglitazone) .
Changes in serum lipids have been observed following treatment with Avandia (Rosiglitazone)
in adults . Small
changes in serum lipid parameters were reported in children treated with Avandia (Rosiglitazone)
for 24 weeks.
In pre-approval clinical studies in 4,598 patients treated with Avandia (Rosiglitazone)
(3,600 patient-years of exposure) and in a long-term 4- to 6-year study in 1,456
patients treated with Avandia (Rosiglitazone) (4,954 patient-years exposure), there was no
evidence of drug-induced hepatotoxicity.
In pre-approval controlled trials, 0.2% of patients treated with Avandia (Rosiglitazone) had
elevations in ALT >3X the upper limit of normal compared to 0.2% on placebo
and 0.5% on active comparators. The ALT elevations in patients treated with
Avandia (Rosiglitazone) were reversible. Hyperbilirubinemia was found in 0.3% of patients
treated with Avandia (Rosiglitazone) compared with 0.9% treated with placebo and 1% in patients
treated with active comparators. In pre-approval clinical trials, there were no
cases of idiosyncratic drug reactions leading to hepatic failure.
In the 4- to 6-year ADOPT trial, patients treated with Avandia (Rosiglitazone) (4,954
patient-years exposure), glyburide (4,244 patient-years exposure), or metformin
(4,906 patient-years exposure), as monotherapy, had the same rate of ALT
increase to greater than 3X upper limit of normal (0.3 per 100 patient-years exposure).
In addition to adverse reactions reported from clinical trials,
the events described below have been identified during post-approval use of
Avandia (Rosiglitazone) . Because these events are reported voluntarily from a population of
unknown size, it is not possible to reliably estimate their frequency or to
always establish a causal relationship to drug exposure.
In patients receiving thiazolidinedione therapy, serious adverse events with
or without a fatal outcome, potentially related to volume expansion (e.g.,
congestive heart failure, pulmonary edema, and pleural effusions) have been
reported .
There are postmarketing reports with Avandia (Rosiglitazone) of hepatitis, hepatic enzyme
elevations to 3 or more times the upper limit of normal, and hepatic failure
with and without fatal outcome, although causality has not been established.
There are postmarketing reports with Avandia (Rosiglitazone) of rash, pruritus, urticaria,
angioedema, anaphylactic reaction, Stevens-Johnson syndrome, and new onset or
worsening diabetic macular edema with decreased visual acuity .
Avandia (Rosiglitazone) Drug Interactions
An inhibitor of CYP2C8 (e.g., gemfibrozil) may increase the AUC
of rosiglitazone and an inducer of CYP2C8 (e.g., rifampin) may decrease the AUC
of rosiglitazone. Therefore, if an inhibitor or an inducer of CYP2C8 is started
or stopped during treatment with rosiglitazone, changes in diabetes treatment
may be needed based upon clinical response.
Avandia (Rosiglitazone) Use In Specific Populations
Pregnancy Category C.
All pregnancies have a background risk of birth defects, loss, or other
adverse outcome regardless of drug exposure. This background risk is increased
in pregnancies complicated by hyperglycemia and may be decreased with good
metabolic control. It is essential for patients with diabetes or history of
gestational diabetes to maintain good metabolic control before conception and
throughout pregnancy. Careful monitoring of glucose control is essential in such
patients. Most experts recommend that insulin monotherapy be used during
pregnancy to maintain blood glucose levels as close to normal as possible.
Rosiglitazone has been reported to cross the human placenta and be detectable
in fetal tissue. The clinical significance of these findings is unknown. There
are no adequate and well-controlled studies in pregnant women. Avandia (Rosiglitazone) should
not be used during pregnancy.
There was no effect on implantation or the embryo with rosiglitazone
treatment during early pregnancy in rats, but treatment during mid-late
gestation was associated with fetal death and growth retardation in both rats
and rabbits. Teratogenicity was not observed at doses up to 3 mg/kg in rats and
100 mg/kg in rabbits (approximately 20 and 75 times human AUC at the maximum
recommended human daily dose, respectively). Rosiglitazone caused placental
pathology in rats (3 mg/kg/day). Treatment of rats during gestation through
lactation reduced litter size, neonatal viability, and postnatal growth, with
growth retardation reversible after puberty. For effects on the placenta,
embryo/fetus, and offspring, the no-effect dose was 0.2 mg/kg/day in rats and 15
mg/kg/day in rabbits. These no-effect levels are approximately 4 times human AUC
at the maximum recommended human daily dose. Rosiglitazone reduced the number of
uterine implantations and live offspring when juvenile female rats were treated
at 40 mg/kg/day from 27 days of age through to sexual maturity (approximately
68 times human AUC at the maximum recommended daily dose). The no-effect level
was 2 mg/kg/day (approximately 4 times human AUC at the maximum recommended
daily dose). There was no effect on pre- or post-natal survival or growth.
The effect of rosiglitazone on labor and delivery in humans is
not known.
Drug-related material was detected in milk from lactating rats.
It is not known whether Avandia (Rosiglitazone) is excreted in human milk. Because many drugs
are excreted in human milk, Avandia (Rosiglitazone) should not be administered to a nursing
woman.
After placebo run-in including diet counseling, children with
type 2 diabetes mellitus, aged 10 to 17 years and with a baseline mean body mass
index (BMI) of 33 kg/m, were randomized to treatment
with 2 mg twice daily of Avandia (Rosiglitazone) (n = 99) or 500 mg twice daily of metformin
(n = 101) in a 24-week, double-blind clinical trial. As expected, FPG decreased
in patients naïve to diabetes medication (n = 104) and increased in patients
withdrawn from prior medication (usually metformin) (n = 90) during the run-in
period. After at least 8 weeks of treatment, 49% of patients treated with
Avandia (Rosiglitazone) and 55% of metformin-treated patients had their dose doubled if FPG
>126 mg/dL. For the overall intent-to-treat population, at week 24, the mean
change from baseline in HbA1c was -0.14% with Avandia (Rosiglitazone) and -0.49% with metformin.
There was an insufficient number of patients in this study to establish
statistically whether these observed mean treatment effects were similar or
different. Treatment effects differed for patients naïve to therapy with
antidiabetic drugs and for patients previously treated with antidiabetic therapy
(Table 6).
* Change from baseline means are least squares means adjusting for baseline HbA1c,
gender, and region.
Treatment differences depended on baseline BMI or weight such that the
effects of Avandia (Rosiglitazone) and metformin appeared more closely comparable among heavier
patients. The median weight gain was 2.8 kg with rosiglitazone and 0.2 kg with
metformin .
Fifty-four percent of patients treated with rosiglitazone and 32% of patients
treated with metformin gained ≥2 kg, and 33% of patients treated with
rosiglitazone and 7% of patients treated with metformin gained ≥5 kg on
study.
Figure 3. Mean HbA1c Over Time in a 24-Week Study of
Avandia (Rosiglitazone) and Metformin in Pediatric Patients — Drug-Naïve Subgroup
Results of the population pharmacokinetic analysis showed that
age does not significantly affect the pharmacokinetics of rosiglitazone . Therefore, no dosage
adjustments are required for the elderly. In controlled clinical trials, no
overall differences in safety and effectiveness between older (greater than or equal to 65 years) and
younger (less than 65 years) patients were observed.
Avandia (Rosiglitazone) Overdosage
Limited data are available with regard to overdosage in humans. In clinical
studies in volunteers, Avandia (Rosiglitazone) has been administered at single oral doses of up
to 20 mg and was well-tolerated. In the event of an overdose, appropriate
supportive treatment should be initiated as dictated by the patient’s clinical
status.
Avandia (Rosiglitazone) Description
Avandia (Rosiglitazone) (rosiglitazone maleate) is an oral antidiabetic agent
which acts primarily by increasing insulin sensitivity. Avandia (Rosiglitazone) improves
glycemic control while reducing circulating insulin levels.
Rosiglitazone maleate is not chemically or functionally related to the
sulfonylureas, the biguanides, or the alpha-glucosidase inhibitors.
The molecular formula is CHNOS•CHO.
Rosiglitazone maleate is a white to off-white solid with a melting point range
of 122° to 123°C. The pKa values of rosiglitazone maleate are 6.8 and 6.1. It is
readily soluble in ethanol and a buffered aqueous solution with pH of 2.3;
solubility decreases with increasing pH in the physiological range.
Each pentagonal film-coated TILTAB tablet contains rosiglitazone maleate
equivalent to rosiglitazone, 2 mg, 4 mg, or 8 mg, for oral administration.
Inactive ingredients are: Hypromellose 2910, lactose monohydrate, magnesium
stearate, microcrystalline cellulose, polyethylene glycol 3000, sodium starch
glycolate, titanium dioxide, triacetin, and 1 or more of the following:
Synthetic red and yellow iron oxides and talc.
Avandia (Rosiglitazone) Clinical Pharmacology
Rosiglitazone, a member of the thiazolidinedione class of
antidiabetic agents, improves glycemic control by improving insulin sensitivity.
Rosiglitazone is a highly selective and potent agonist for the peroxisome
proliferator-activated receptor-gamma (PPARγ). In humans, PPAR receptors are
found in key target tissues for insulin action such as adipose tissue, skeletal
muscle, and liver. Activation of PPARγ nuclear receptors regulates the
transcription of insulin-responsive genes involved in the control of glucose
production, transport, and utilization. In addition, PPARγ-responsive genes also
participate in the regulation of fatty acid metabolism.
Insulin resistance is a common feature characterizing the pathogenesis of
type 2 diabetes. The antidiabetic activity of rosiglitazone has been
demonstrated in animal models of type 2 diabetes in which hyperglycemia and/or
impaired glucose tolerance is a consequence of insulin resistance in target
tissues. Rosiglitazone reduces blood glucose concentrations and reduces
hyperinsulinemia in the ob/ob obese mouse, db/db diabetic mouse, and fa/fa fatty
Zucker rat.
In animal models, the antidiabetic activity of rosiglitazone was shown to be
mediated by increased sensitivity to insulin’s action in the liver, muscle, and
adipose tissues. Pharmacological studies in animal models indicate that
rosiglitazone inhibits hepatic gluconeogenesis. The expression of the
insulin-regulated glucose transporter GLUT-4 was increased in adipose tissue.
Rosiglitazone did not induce hypoglycemia in animal models of type 2 diabetes
and/or impaired glucose tolerance.
Patients with lipid abnormalities were not excluded from clinical
trials of Avandia (Rosiglitazone) . In all 26-week controlled trials, across the recommended dose
range, Avandia (Rosiglitazone) as monotherapy was associated with increases in total
cholesterol, LDL, and HDL and decreases in free fatty acids. These changes were
statistically significantly different from placebo or glyburide controls (Table
7).
Increases in LDL occurred primarily during the first 1 to 2 months of therapy
with Avandia (Rosiglitazone) and LDL levels remained elevated above baseline throughout the
trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL
ratio peaked after 2 months of therapy and then appeared to decrease over time.
Because of the temporal nature of lipid changes, the 52-week
glyburide-controlled study is most pertinent to assess long-term effects on
lipids. At baseline, week 26, and week 52, mean LDL/HDL ratios were 3.1, 3.2,
and 3.0, respectively, for Avandia (Rosiglitazone) 4 mg twice daily. The corresponding values
for glyburide were 3.2, 3.1, and 2.9. The differences in change from baseline
between Avandia (Rosiglitazone) and glyburide at week 52 were statistically significant.
The pattern of LDL and HDL changes following therapy with Avandia (Rosiglitazone) in
combination with other hypoglycemic agents were generally similar to those seen
with Avandia (Rosiglitazone) in monotherapy.
The changes in triglycerides during therapy with Avandia (Rosiglitazone) were variable and
were generally not statistically different from placebo or glyburide controls.
Maximum plasma concentration (C) and
the area under the curve (AUC) of rosiglitazone increase in a dose-proportional
manner over the therapeutic dose range (Table 8). The elimination half-life is 3
to 4 hours and is independent of dose.
The absolute bioavailability of rosiglitazone is 99%. Peak plasma
concentrations are observed about 1 hour after dosing. Administration of
rosiglitazone with food resulted in no change in overall exposure (AUC), but
there was an approximately 28% decrease in C and a
delay in T (1.75 hours). These changes are not likely
to be clinically significant; therefore, Avandia (Rosiglitazone) may be administered with or
without food.
The mean (CV%) oral volume of distribution (Vss/F) of rosiglitazone is
approximately 17.6 (30%) liters, based on a population pharmacokinetic analysis.
Rosiglitazone is approximately 99.8% bound to plasma proteins, primarily
albumin.
Rosiglitazone is extensively metabolized with no unchanged drug excreted in
the urine. The major routes of metabolism were N-demethylation and
hydroxylation, followed by conjugation with sulfate and glucuronic acid. All the
circulating metabolites are considerably less potent than parent and, therefore,
are not expected to contribute to the insulin-sensitizing activity of
rosiglitazone.
In vitro data demonstrate that rosiglitazone is predominantly metabolized by
Cytochrome P450 (CYP) isoenzyme 2C8, with CYP2C9 contributing as a minor
pathway.
Following oral or intravenous administration of [C]rosiglitazone maleate, approximately 64% and 23% of the
dose was eliminated in the urine and in the feces, respectively. The plasma
half-life of [C]related material ranged from 103 to
158 hours.
Population pharmacokinetic analyses from 3 large clinical trials including
642 men and 405 women with type 2 diabetes (aged 35 to 80 years) showed that the
pharmacokinetics of rosiglitazone are not influenced by age, race, smoking, or
alcohol consumption. Both oral clearance (CL/F) and oral steady-state volume of
distribution (Vss/F) were shown to increase with increases in body weight. Over
the weight range observed in these analyses (50 to 150 kg), the range of
predicted CL/F and Vss/F values varied by less than 1.7-fold and less than 2.3-fold,
respectively. Additionally, rosiglitazone CL/F was shown to be influenced by
both weight and gender, being lower (about 15%) in female patients.
Results of the population pharmacokinetic analysis (n = 716 less than 65 years;
n = 331 greater than or equal to 65 years) showed that age does not significantly affect the
pharmacokinetics of rosiglitazone.
Results of the population pharmacokinetics analysis showed that the mean oral
clearance of rosiglitazone in female patients (n = 405) was approximately 6%
lower compared to male patients of the same body weight (n = 642).
As monotherapy and in combination with metformin, Avandia (Rosiglitazone) improved glycemic
control in both males and females. In metformin combination studies, efficacy
was demonstrated with no gender differences in glycemic response.
In monotherapy studies, a greater therapeutic response was observed in
females; however, in more obese patients, gender differences were less evident.
For a given body mass index (BMI), females tend to have a greater fat mass than
males. Since the molecular target PPARγ is expressed in adipose tissues, this
differentiating characteristic may account, at least in part, for the greater
response to Avandia (Rosiglitazone) in females. Since therapy should be individualized, no dose
adjustments are necessary based on gender alone.
Unbound oral clearance of rosiglitazone was significantly lower in patients
with moderate to severe liver disease (Child-Pugh Class B/C) compared to healthy
subjects. As a result, unbound C and AUC were increased 2- and 3-fold, respectively. Elimination
half-life for rosiglitazone was about 2 hours longer in patients with liver
disease, compared to healthy subjects.
Therapy with Avandia (Rosiglitazone) should not be initiated if the patient exhibits clinical
evidence of active liver disease or increased serum transaminase levels (ALT
greater than 2.5X upper limit of normal) at baseline .
Pharmacokinetic parameters of rosiglitazone in pediatric patients were
established using a population pharmacokinetic analysis with sparse data from 96
pediatric patients in a single pediatric clinical trial including 33 males and
63 females with ages ranging from 10 to 17 years (weights ranging from 35 to
178.3 kg). Population mean CL/F and V/F of rosiglitazone were 3.15 L/hr and 13.5
L, respectively. These estimates of CL/F and V/F were consistent with the
typical parameter estimates from a prior adult population analysis.
There are no clinically relevant differences in the pharmacokinetics of
rosiglitazone in patients with mild to severe renal impairment or in
hemodialysis-dependent patients compared to subjects with normal renal function.
No dosage adjustment is therefore required in such patients receiving Avandia (Rosiglitazone) .
Since metformin is contraindicated in patients with renal impairment,
coadministration of metformin with Avandia (Rosiglitazone) is contraindicated in these
patients.
Results of a population pharmacokinetic analysis including subjects of
Caucasian, black, and other ethnic origins indicate that race has no influence
on the pharmacokinetics of rosiglitazone.
In vitro drug metabolism studies suggest that rosiglitazone does not inhibit
any of the major P450 enzymes at clinically relevant concentrations. In vitro
data demonstrate that rosiglitazone is predominantly metabolized by CYP2C8, and
to a lesser extent, 2C9. Avandia (Rosiglitazone) (4 mg twice daily) was shown to have no
clinically relevant effect on the pharmacokinetics of nifedipine and oral
contraceptives (ethinyl estradiol and norethindrone), which are predominantly
metabolized by CYP3A4.
Concomitant administration of gemfibrozil (600 mg twice daily), an inhibitor
of CYP2C8, and rosiglitazone (4 mg once daily) for 7 days increased
rosiglitazone AUC by 127%, compared to the administration of rosiglitazone (4 mg
once daily) alone. Given the potential for dose-related adverse events with
rosiglitazone, a decrease in the dose of rosiglitazone may be needed when
gemfibrozil is introduced .
Rifampin administration (600 mg once a day), an inducer of CYP2C8, for 6 days
is reported to decrease rosiglitazone AUC by 66%, compared to the administration
of rosiglitazone (8 mg) alone .
Avandia (Rosiglitazone) (2 mg twice daily) taken concomitantly with glyburide (3.75 to
10 mg/day) for 7 days did not alter the mean steady-state 24-hour plasma glucose
concentrations in diabetic patients stabilized on glyburide therapy. Repeat
doses of Avandia (Rosiglitazone) (8 mg once daily) for 8 days in healthy adult Caucasian
subjects caused a decrease in glyburide AUC and C of
approximately 30%. In Japanese subjects, glyburide AUC and C slightly increased following coadministration of
Avandia (Rosiglitazone) .
Single oral doses of glimepiride in 14 healthy adult subjects had no
clinically significant effect on the steady-state pharmacokinetics of Avandia (Rosiglitazone) .
No clinically significant reductions in glimepiride AUC and C were observed after repeat doses of Avandia (Rosiglitazone) (8 mg once
daily) for 8 days in healthy adult subjects.
Concurrent administration of Avandia (Rosiglitazone) (2 mg twice daily) and metformin (500 mg
twice daily) in healthy volunteers for 4 days had no effect on the steady-state
pharmacokinetics of either metformin or rosiglitazone.
Coadministration of acarbose (100 mg three times daily) for 7 days in healthy
volunteers had no clinically relevant effect on the pharmacokinetics of a single
oral dose of Avandia (Rosiglitazone) .
Repeat oral dosing of Avandia (Rosiglitazone) (8 mg once daily) for 14 days did not alter the
steady-state pharmacokinetics of digoxin (0.375 mg once daily) in healthy
volunteers.
Repeat dosing with Avandia (Rosiglitazone) had no clinically relevant effect on the
steady-state pharmacokinetics of warfarin enantiomers.
A single administration of a moderate amount of alcohol did not increase the
risk of acute hypoglycemia in type 2 diabetes mellitus patients treated with
Avandia (Rosiglitazone) .
Pretreatment with ranitidine (150 mg twice daily for 4 days) did not alter
the pharmacokinetics of either single oral or intravenous doses of rosiglitazone
in healthy volunteers. These results suggest that the absorption of oral
rosiglitazone is not altered in conditions accompanied by increases in
gastrointestinal pH.
Avandia (Rosiglitazone) Nonclinical Toxicology
A 2-year carcinogenicity study was conducted in Charles River CD-1 mice at
doses of 0.4, 1.5, and 6 mg/kg/day in the diet (highest dose equivalent to
approximately 12 times human AUC at the maximum recommended human daily dose).
Sprague-Dawley rats were dosed for 2 years by oral gavage at doses of 0.05, 0.3,
and 2 mg/kg/day (highest dose equivalent to approximately 10 and 20 times human
AUC at the maximum recommended human daily dose for male and female rats,
respectively).
Rosiglitazone was not carcinogenic in the mouse. There was an increase in
incidence of adipose hyperplasia in the mouse at doses ≥1.5 mg/kg/day
(approximately 2 times human AUC at the maximum recommended human daily dose).
In rats, there was a significant increase in the incidence of benign adipose
tissue tumors (lipomas) at doses ≥0.3 mg/kg/day (approximately 2 times human AUC
at the maximum recommended human daily dose). These proliferative changes in
both species are considered due to the persistent pharmacological
overstimulation of adipose tissue.
Rosiglitazone was not mutagenic or clastogenic in the in vitro bacterial
assays for gene mutation, the in vitro chromosome aberration test in human
lymphocytes, the in vivo mouse micronucleus test, and the in vivoin vitro rat UDS assay. There was a small (about 2-fold)
increase in mutation in the in vitro mouse lymphoma assay in the presence of
metabolic activation.
Rosiglitazone had no effects on mating or fertility of male rats given up to
40 mg/kg/day (approximately 116 times human AUC at the maximum recommended human
daily dose). Rosiglitazone altered estrous cyclicity (2 mg/kg/day) and reduced
fertility (40 mg/kg/day) of female rats in association with lower plasma levels
of progesterone and estradiol (approximately 20 and 200 times human AUC at the
maximum recommended human daily dose, respectively). No such effects were noted
at 0.2 mg/kg/day (approximately 3 times human AUC at the maximum recommended
human daily dose). In juvenile rats dosed from 27 days of age through to sexual
maturity (at up to 40 mg/kg/day), there was no effect on male reproductive
performance, or on estrous cyclicity, mating performance or pregnancy incidence
in females (approximately 68 times human AUC at the maximum recommended human
daily dose). In monkeys, rosiglitazone (0.6 and 4.6 mg/kg/day; approximately 3
and 15 times human AUC at the maximum recommended human daily dose,
respectively) diminished the follicular phase rise in serum estradiol with
consequential reduction in the luteinizing hormone surge, lower luteal phase
progesterone levels, and amenorrhea. The mechanism for these effects appears to
be direct inhibition of ovarian steroidogenesis.
Heart weights were increased in mice (3 mg/kg/day), rats
(5 mg/kg/day), and dogs (2 mg/kg/day) with rosiglitazone treatments
(approximately 5, 22, and 2 times human AUC at the maximum recommended human
daily dose, respectively). Effects in juvenile rats were consistent with those
seen in adults. Morphometric measurement indicated that there was hypertrophy in
cardiac ventricular tissues, which may be due to increased heart work as a
result of plasma volume expansion.
Avandia (Rosiglitazone) Clinical Studies
In clinical studies, treatment with Avandia (Rosiglitazone) resulted in an
improvement in glycemic control, as measured by FPG and HbA1c, with a concurrent
reduction in insulin and C-peptide. Postprandial glucose and insulin were also
reduced. This is consistent with the mechanism of action of Avandia (Rosiglitazone) as an
insulin sensitizer.
The maximum recommended daily dose is 8 mg. Dose-ranging studies suggested
that no additional benefit was obtained with a total daily dose of 12 mg.
A total of 2,315 patients with type 2 diabetes, previously treated with diet
alone or antidiabetic medication(s), were treated with Avandia (Rosiglitazone) as monotherapy in
6 double-blind studies, which included two 26-week placebo-controlled studies,
one 52-week glyburide-controlled study, and 3 placebo-controlled dose-ranging
studies of 8 to 12 weeks duration. Previous antidiabetic medication(s) were
withdrawn and patients entered a 2 to 4 week placebo run-in period prior to
randomization.
Two 26-week, double-blind, placebo-controlled trials, in patients with type 2
diabetes (n = 1,401) with inadequate glycemic control (mean baseline FPG
approximately 228 mg/dL [101 to 425 mg/dL] and mean baseline HbA1c 8.9% [5.2% to
16.2%]), were conducted. Treatment with Avandia (Rosiglitazone) produced statistically
significant improvements in FPG and HbA1c compared to baseline and relative to
placebo. Data from one of these studies are summarized in Table 9.
When administered at the same total daily dose, Avandia (Rosiglitazone) was generally more
effective in reducing FPG and HbA1c when administered in divided doses twice
daily compared to once daily doses. However, for HbA1c, the difference between
the 4 mg once daily and 2 mg twice daily doses was not statistically
significant.
Long-term maintenance of effect was evaluated in a 52-week, double-blind,
glyburide-controlled trial in patients with type 2 diabetes. Patients were
randomized to treatment with Avandia (Rosiglitazone) 2 mg twice daily (N = 195) or Avandia (Rosiglitazone) 4 mg
twice daily (N = 189) or glyburide (N = 202) for 52 weeks. Patients receiving
glyburide were given an initial dosage of either 2.5 mg/day or 5.0 mg/day. The
dosage was then titrated in 2.5 mg/day increments over the next 12 weeks, to a
maximum dosage of 15.0 mg/day in order to optimize glycemic control. Thereafter,
the glyburide dose was kept constant.
Figure 5. Mean HbA1c Over Time in a 52-Week
Glyburide-Controlled Study
Hypoglycemia was reported in 12.1% of glyburide-treated patients versus 0.5%
(2 mg twice daily) and 1.6% (4 mg twice daily) of patients treated with Avandia (Rosiglitazone) .
The improvements in glycemic control were associated with a mean weight gain of
1.75 kg and 2.95 kg for patients treated with 2 mg and 4 mg twice daily of
Avandia (Rosiglitazone) , respectively, versus 1.9 kg in glyburide-treated patients. In patients
treated with Avandia (Rosiglitazone) , C-peptide, insulin, pro-insulin, and pro-insulin split
products were significantly reduced in a dose-ordered fashion, compared to an
increase in the glyburide-treated patients.
A Diabetes Outcome Progression Trial (ADOPT) was a multicenter, double-blind,
controlled trial (N = 4,351) conducted over 4 to 6 years to compare the safety
and efficacy of Avandia (Rosiglitazone) , metformin, and glyburide monotherapy in patients
recently diagnosed with type 2 diabetes mellitus (≤3 years) inadequately
controlled with diet and exercise. The mean age of patients in this trial was
57 years and the majority of patients (83%) had no known history of
cardiovascular disease. The mean baseline FPG and HbA1c were 152 mg/dL and 7.4%,
respectively. Patients were randomized to receive either Avandia (Rosiglitazone) 4 mg once
daily, glyburide 2.5 mg once daily, or metformin 500 mg once daily, and doses
were titrated to optimal glycemic control up to a maximum of 4 mg twice daily
for Avandia (Rosiglitazone) , 7.5 mg twice daily for glyburide, and 1,000 mg twice daily for
metformin. The primary efficacy outcome was time to consecutive FPG
>180 mg/dL after at least 6 weeks of treatment at the maximum tolerated dose
of study medication or time to inadequate glycemic control, as determined by an
independent adjudication committee.
The cumulative incidence of the primary efficacy outcome at 5 years was 15%
with Avandia (Rosiglitazone) , 21% with metformin, and 34% with glyburide (hazard ratio 0.68 [95%
CI 0.55, 0.85] versus metformin, HR 0.37 [95% CI 0.30, 0.45] versus
glyburide).
Cardiovascular and adverse event data (including effects on body weight and
bone fracture) from ADOPT for Avandia (Rosiglitazone) , metformin, and glyburide are described in
and
, respectively. As with all
medications, efficacy results must be considered together with safety
information to assess the potential benefit and risk for an individual
patient.
The addition of Avandia (Rosiglitazone) to either metformin or sulfonylurea
resulted in significant reductions in hyperglycemia compared to either of these
agents alone. These results are consistent with an additive effect on glycemic
control when Avandia (Rosiglitazone) is used as combination therapy.
A total of 670 patients with type 2 diabetes participated in two 26-week,
randomized, double-blind, placebo/active-controlled studies designed to assess
the efficacy of Avandia (Rosiglitazone) in combination with metformin. Avandia (Rosiglitazone) , administered in
either once daily or twice daily dosing regimens, was added to the therapy of
patients who were inadequately controlled on a maximum dose (2.5 grams/day) of
metformin.
In one study, patients inadequately controlled on 2.5 grams/day of metformin
(mean baseline FPG 216 mg/dL and mean baseline HbA1c 8.8%) were randomized to
receive 4 mg of Avandia (Rosiglitazone) once daily, 8 mg of Avandia (Rosiglitazone) once daily, or placebo in
addition to metformin. A statistically significant improvement in FPG and HbA1c
was observed in patients treated with the combinations of metformin and 4 mg of
Avandia (Rosiglitazone) once daily and 8 mg of Avandia (Rosiglitazone) once daily, versus patients continued on
metformin alone (Table 10).
In a second 26-week study, patients with type 2 diabetes inadequately
controlled on 2.5 grams/day of metformin who were randomized to receive the
combination of Avandia (Rosiglitazone) 4 mg twice daily and metformin (N = 105) showed a
statistically significant improvement in glycemic control with a mean treatment
effect for FPG of -56 mg/dL and a mean treatment effect for HbA1c of -0.8% over
metformin alone. The combination of metformin and Avandia (Rosiglitazone) resulted in lower
levels of FPG and HbA1c than either agent alone.
Patients who were inadequately controlled on a maximum dose (2.5 grams/day)
of metformin and who were switched to monotherapy with Avandia (Rosiglitazone) demonstrated loss
of glycemic control, as evidenced by increases in FPG and HbA1c. In this group,
increases in LDL and VLDL were also seen.
A total of 3,457 patients with type 2 diabetes participated in ten 24- to
26-week randomized, double-blind, placebo/active-controlled studies and one
2-year double-blind, active-controlled study in elderly patients designed to
assess the efficacy and safety of Avandia (Rosiglitazone) in combination with a sulfonylurea.
Avandia (Rosiglitazone) 2 mg, 4 mg, or 8 mg daily was administered, either once daily (3
studies) or in divided doses twice daily (7 studies), to patients inadequately
controlled on a submaximal or maximal dose of sulfonylurea.
In these studies, the combination of Avandia (Rosiglitazone) 4 mg or 8 mg daily (administered
as single or twice daily divided doses) and a sulfonylurea significantly reduced
FPG and HbA1c compared to placebo plus sulfonylurea or further up-titration of
the sulfonylurea. Table 11 shows pooled data for 8 studies in which Avandia (Rosiglitazone)
added to sulfonylurea was compared to placebo plus sulfonylurea.
One of the 24- to 26-week studies included patients who were inadequately
controlled on maximal doses of glyburide and switched to 4 mg of Avandia (Rosiglitazone) daily
as monotherapy; in this group, loss of glycemic control was demonstrated, as
evidenced by increases in FPG and HbA1c.
In a 2-year double-blind study, elderly patients (aged 59 to 89 years) on
half-maximal sulfonylurea (glipizide 10 mg twice daily) were randomized to the
addition of Avandia (Rosiglitazone) (n = 115, 4 mg once daily to 8 mg as needed) or to continued
up-titration of glipizide (n = 110), to a maximum of 20 mg twice daily. Mean
baseline FPG and HbA1c were 157 mg/dL and 7.72%, respectively, for the Avandia (Rosiglitazone)
plus glipizide arm and 159 mg/dL and 7.65%, respectively, for the glipizide
up-titration arm. Loss of glycemic control (FPG ≥180 mg/dL) occurred in a
significantly lower proportion of patients (2%) on Avandia (Rosiglitazone) plus glipizide
compared to patients in the glipizide up-titration arm (28.7%). About 78% of the
patients on combination therapy completed the 2 years of therapy while only 51%
completed on glipizide monotherapy. The effect of combination therapy on FPG and
HbA1c was durable over the 2-year study period, with patients achieving a mean
of 132 mg/dL for FPG and a mean of 6.98% for HbA1c compared to no change on the
glipizide arm.
In two 24- to 26-week, double-blind, placebo-controlled, studies
designed to assess the efficacy and safety of Avandia (Rosiglitazone) in combination with
sulfonylurea plus metformin, Avandia (Rosiglitazone) 4 mg or 8 mg daily, was administered in
divided doses twice daily, to patients inadequately controlled on submaximal
(10 mg) and maximal (20 mg) doses of glyburide and maximal dose of metformin
(2 g/day). A statistically significant improvement in FPG and HbA1c was observed
in patients treated with the combinations of sulfonylurea plus metformin and
4 mg of Avandia (Rosiglitazone) and 8 mg of Avandia (Rosiglitazone) versus patients continued on sulfonylurea
plus metformin, as shown in Table 12.
Avandia (Rosiglitazone) How Supplied/storage And Handling
Each pentagonal film-coated TILTAB tablet contains rosiglitazone
as the maleate as follows: 2 mg–pink, debossed with SB on one side and 2 on the
other; 4 mg–orange, debossed with SB on one side and 4 on the other; 8
mg–red-brown, debossed with SB on one side and 8 on the other.
2 mg bottles of 30: NDC 54868-5249-02 mg bottles of 60: NDC 54868-5249-1
4 mg bottles of 30: NDC 54868-4198-04 mg bottles of 60: NDC 54868-4198-1
8 mg bottles of 30: NDC 54868-4221-0
Store at 25°C (77°F); excursions 15° to 30°C (59° to 86°F). Dispense in a
tight, light-resistant container.
Avandia (Rosiglitazone) Patient Counseling Information
Patients should be informed of the following:
See separate leaflet.
Avandia (Rosiglitazone) and TILTAB are registered trademarks of
GlaxoSmithKline.
GlaxoSmithKline
Research Triangle Park, NC 27709
©2009, GlaxoSmithKline. All rights reserved.
Read this Medication Guide carefully before you start taking Avandia (Rosiglitazone) and each
time you get a refill. There may be new information. This information does not
take the place of talking with your doctor about your medical condition or your
treatment. If you have any questions about Avandia (Rosiglitazone) , ask your doctor or
pharmacist.
Avandia (Rosiglitazone) is a prescription medicine to treat adults with diabetes. It helps to
control high blood sugar. (See “What is Avandia (Rosiglitazone) ?”). It is important that you
take Avandia (Rosiglitazone) exactly how it is prescribed by your doctor to best treat your
diabetes.
Avandia (Rosiglitazone) may cause serious side effects, including:
Call your doctor right away if you have any of the following:
Avandia (Rosiglitazone) may raise the risk of heart problems related to reduced blood flow to
the heart. These include possible increases in the risk of heart-related chest
pain (angina) or "heart attack" (myocardial infarction). This risk seemed to be
higher in people who took Avandia (Rosiglitazone) with insulin or with nitrate medicines. Most
people who take insulin or nitrate medicines should not also take Avandia (Rosiglitazone) .
Avandia (Rosiglitazone) can have other serious side effects. Be sure to read the section
below “What are possible side effects of Avandia (Rosiglitazone) ?”.
Avandia (Rosiglitazone) is a prescription medicine used with diet and exercise to treat
adults with type 2 (“adult-onset” or “non-insulin dependent”) diabetes mellitus
(“high blood sugar”). Avandia (Rosiglitazone) helps to control high blood sugar. Avandia (Rosiglitazone) may be
used alone or with other diabetes medicines. Avandia (Rosiglitazone) can help your body respond
better to insulin made in your body. Avandia (Rosiglitazone) does not cause your body to make
more insulin.
Many people with heart failure should not start taking Avandia (Rosiglitazone) . See “What
should I tell my doctor before taking Avandia (Rosiglitazone) ?”.
Before starting Avandia (Rosiglitazone) , ask your doctor about what the choices are for
diabetes medicines, and what the expected benefits and possible risks are for
you in particular.
Before taking Avandia (Rosiglitazone) , tell your doctor about all your medical conditions,
including if you:
Tell your doctor about all the medicines you take including prescription and
non-prescription medicines, vitamins or herbal supplements. Avandia (Rosiglitazone) and certain
other medicines can affect each other and may lead to serious side effects
including high or low blood sugar, or heart problems. Especially tell your
doctor if you take:
Know the medicines you take. Keep a list of your medicines and show it to
your doctor and pharmacist before you start a new medicine. They will tell you
if it is alright to take Avandia (Rosiglitazone) with other medicines.
The most common side effects of Avandia (Rosiglitazone) reported in clinical trials included
cold-like symptoms and headache.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use Avandia (Rosiglitazone) for a condition for which it was not
prescribed. Do not give Avandia (Rosiglitazone) to other people, even if they have the same
symptoms you have. It may harm them.
This Medication Guide summarizes important information about Avandia (Rosiglitazone) . If you
would like more information, talk with your doctor. You can ask your doctor or
pharmacist for information about Avandia (Rosiglitazone) that is written for healthcare
professionals. You can also find out more about Avandia (Rosiglitazone) by calling
1-888-825-5249 or visiting the website www.Avandia (Rosiglitazone) .com.
Active Ingredient: Rosiglitazone maleate.
Inactive Ingredients: Hypromellose 2910, lactose monohydrate, magnesium
stearate, microcrystalline cellulose, polyethylene glycol 3000, sodium starch
glycolate, titanium dioxide, triacetin, and 1 or more of the following:
Synthetic red and yellow iron oxides and talc.
Always check to make sure that the medicine you are taking is the correct
one. Avandia (Rosiglitazone) tablets are triangles with rounded corners and look like this:
2 mg strength tablets – pink with “SB” on one side and “2” on the other.
4 mg strength tablets – orange with “SB” on one side and “4” on the
other.
8 mg strength tablets – red-brown with “SB” on one side and “8” on the
other.
Avandia (Rosiglitazone) is a registered trademark of GlaxoSmithKline.
REZULIN is a registered trademark of Parke-Davis Pharmaceuticals Ltd.
GlaxoSmithKline
Research Triangle Park, NC 27709
©2008, GlaxoSmithKline. All rights reserved.
October 2008
AVD:4MG
Avandia (Rosiglitazone) Principal Display Panel
Avandia (Rosiglitazone)
ROSIGLITAZONE MALEATE TABLETS
Avandia (Rosiglitazone)
ROSIGLITAZONE MALEATE TABLETS
Avandia (Rosiglitazone)
ROSIGLITAZONE MALEATE TABLETS
