Possible side effects
Heart failure. Avandia can cause your body to keep extra fluid (fluid retention), which leads to swelling and weight gain. Extra body fluid can make some heart problems worse or leadto heart failure.
Swelling (edema) from fluid retention. Call your doctor right away if you have symptoms such as:
- swelling or fluid retention, especially in the ankles or legs
- shortness of breath or trouble breathing, especially when you lie down
- an unusually fast increase in weight
- unusual tiredness
Low blood sugar (hypoglycemia). Lightheadedness, dizziness, shakiness or hunger may mean that your blood sugar is too low. This can happen if you skip meals, if you use another medicine that lowers blood sugar, or if you have certain medical problems. Call your doctor if low blood sugar levels are a problem for you.
Fractures, usually in the hand, upper arm or foot, in females. Talk to your doctor for advice on how to keep your bones healthy.
Weight gain. Avandia can cause weight gain that may be due to fluid retention or extra body fat. Weight gain can be a serious problem for people with certain conditions including heart problems. Call your doctor if you have an unusually fast increase in weight.
Low red blood cell count (anemia).
Ovulation (release of egg from an ovary in a woman) leading to pregnancy. Ovulation may happen in premenopausal women who do not have regular monthly periods. This can increase the chance of pregnancy.
Liver problems. It is important for your liver to be working normally when you take Avandia. Your doctor should do blood tests to check your liver before you start taking Avandia and during treatment as needed.Call your doctor right away if you have unexplained symptoms such as:
- nausea or vomiting
- stomach pain
- unusual or unexplained tiredness
- loss of appetite
- dark urine
- yellowing of your skin or the whites of your eyes.
The most common side effects of Avandia included cold-like symptoms, injury, and headache.
What other drugs will affect Avandia (Rosiglitazone)?
You may be more likely to have hyperglycemia (high blood sugar) if you are taking Avandia with other drugs that raise blood sugar. Drugs that can raise blood sugar include:
- isoniazid;
- diuretics (water pills);
- steroids (prednisone and others);
- phenothiazines (Compazine and others);
- thyroid medicine (Synthroid and others);
- birth control pills and other hormones;
- seizure medicines (Dilantin and others); and
- diet pills or medicines to treat asthma, colds or allergies.
You may be more likely to have hypoglycemia (low blood sugar) if you are taking Avandia with other drugs that lower blood sugar. Drugs that can lower blood sugar include:
- nonsteroidal anti-inflammatory drugs (NSAIDs);
- aspirin or other salicylates (including Pepto-Bismol);
- sulfa drugs (Bactrim and others);
- a monoamine oxidase inhibitor (MAOI);
- beta-blockers (Tenormin and others); or
- probenecid (Benemid).
Some medications may interact with Avandia. Tell your doctor if you are using any of the following drugs:
- gemfibrozil (Gemcor); or
- rifampin (Rifater, Rifadin, Rimactane).
If you are using any of these drugs, you may not be able to take Avandia, or you may require a dosage adjustment or special monitoring.
There may be other drugs not listed that can affect Avandia. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
What should I avoid while taking Avandia (Rosiglitazone)?
Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.
Avoid alcohol. It lowers blood sugar and may interfere with your diabetes treatment.
Tell your doctor and dentist that you are taking this medication before you undergo any surgery.
Do not take any over-the-counter cough, cold, allergy, pain, or weight-loss medications without first talking to your doctor.
Contraindications
Initiation of Avandia in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated.
Avandia is contraindicated in patients with known hypersensitivity to this product or any of its components.
Warnings
Avandia, 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. In combination with insulin, thiazolidinediones may also increase the risk of other cardiovascular adverse events. Avandia should be discontinued if any deterioration in cardiac status occurs.
Patients with congestive heart failure (CHF) NYHA Class I and II treated with Avandia have an increased risk of cardiovascular events.
Patients treated with combination Avandia and insulin should be monitored for cardiovascular adverse events. This combination therapy should be discontinued in patients who do not respond as manifested by a reduction in HbA1c or insulin dose after 4 to 5 months of therapy or who develop any significant adverse events.
Precautions
Due to its mechanism of action, Avandia is active only in the presence of endogenous insulin. Therefore, Avandia should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Hypoglycemia
Patients receiving Avandia in combination with other hypoglycemic agents may be at risk for hypoglycemia, and a reduction in the dose of the concomitant agent may be necessary.
Edema
Avandia should be used with caution in patients with edema. In a clinical study in healthy volunteers who received 8 mg of Avandia once daily for 8 weeks, there was a statistically significant increase in median plasma volume compared to placebo.
Since thiazolidinediones, including rosiglitazone, can cause fluid retention, which can exacerbate or lead to congestive heart failure, Avandia should be used with caution in patients at risk for heart failure. Patients should be monitored for signs and symptoms of heart failure.
In controlled clinical trials of patients with type 2 diabetes, mild to moderate edema was reported in patients treated with Avandia, and may be dose related. Patients with ongoing edema are more likely to have adverse events associated with edema if started on combination therapy with insulin and Avandia.
Macular Edema
Macular edema has been reported in postmarketing experience in some diabetic patients who were taking Avandia or another thiazolidinedione. Some patients presented with blurred vision or decreased visual acuity, but some patients appear to have been diagnosed on routine ophthalmologic examination. Most patients had peripheral edema at the time macular edema was diagnosed. Some patients had improvement in their macular edema after discontinuation of their thiazolidinedione. Patients with diabetes should have regular eye exams by an ophthalmologist, per the Standards of Care of the American Diabetes Association. Additionally, any diabetic who reports any kind of visual symptom should be promptly referred to an ophthalmologist, regardless of the patient�s underlying medications or other physical findings.
Fractures
In a 4- to 6-year comparative study (ADOPT) of glycemic control with monotherapy in drug-naive patients recently diagnosed with type 2 diabetes mellitus, an increased incidence of bone fracture was noted in female patients taking Avandia. Over the 4- to 6-year period, the incidence of bone fracture in females was 9.3% (60/645) for Avandia versus 3.5% (21/605) for glyburide and 5.1% (30/590) for metformin. This increased incidence was noted after the first year of treatment and persisted during the course of the study. The majority of the fractures in the women who received Avandia occurred in the upper arm, hand, and foot. These sites of fracture are different from those usually associated with postmenopausal osteoporosis (e.g., hip or spine). No increase in fracture rates was observed in men treated with Avandia. The risk of fracture should be considered in the care of patients, especially female patients, treated with Avandia, and attention given to assessing and maintaining bone health according to current standards of care.
Weight Gain
Dose-related weight gain was seen with Avandia alone and in combination with other hypoglycemic agents. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation.
Hematologic
Across all controlled clinical studies in adults, decreases in hemoglobin and hematocrit (mean decreases in individual studies ?1.0 gram/dL and ?3.3%, respectively) were observed for Avandia alone and in combination with other hypoglycemic agents. The changes occurred primarily during the first 3 months following initiation of therapy with Avandia or following a dose increase in Avandia. White blood cell counts also decreased slightly in adult patients treated with Avandia. Small decreases in hemoglobin and hematocrit have also been reported in pediatric patients treated with Avandia. The observed changes may be related to the increased plasma volume observed with treatment with Avandia and may be dose related.
Ovulation
Therapy with Avandia, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. As a result, these patients may be at an increased risk for pregnancy while taking Avandia. Thus, adequate contraception in premenopausal women should be recommended. This possible effect has not been specifically investigated in clinical studies so the frequency of this occurrence is not known.
Although hormonal imbalance has been seen in preclinical studies, the clinical significance of this finding is not known. If unexpected menstrual dysfunction occurs, the benefits of continued therapy with Avandia should be reviewed.
Hepatic Effects
Another drug of the thiazolidinedione class, troglitazone, was associated with idiosyncratic hepatotoxicity, and very rare cases of liver failure, liver transplants, and death were reported during clinical use. In pre-approval controlled clinical trials in patients with type 2 diabetes, troglitazone was more frequently associated with clinically significant elevations in liver enzymes (ALT >3X upper limit of normal) compared to placebo. Very rare cases of reversible jaundice were also reported.
Information For Patients
Carcinogenesis/ Mutagenesis/ Impairment of Fertility
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 vivo/in 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 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.
Animal Toxicology
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.
Pregnancy
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.
Human Data
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 should not be used during pregnancy.
Animal Studies
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.
Nursing Mothers
Drug-related material was detected in milk from lactating rats. It is not known whether Avandia is excreted in human milk. Because many drugs are excreted in human milk, Avandia should not be administered to a nursing woman.
Pediatric Use
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/m2, were randomized to treatment with 2 mg twice daily of Avandia (n = 99) or 500 mg twice daily of metformin (n = 101) in a 24-week, double-blind clinical trial. As expected, fasting plasma glucose (FPG) decreased in patients naive 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 Avandia-treated patients 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 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 naive to therapy with antidiabetic drugs and for patients previously treated with antidiabetic therapy.
Geriatric Use
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 (>65 years) and younger (<65 years) patients were observed.
Product Description
Most important information about Avandia
Pharmacokinetics
Possible Side Effects
More information about AVANDIA (Rosiglitazone):
AVANDIA (Rosiglitazone): What You Should Know
Can Avandia or other drugs prevent diabetes?
Actos beats Avandia in sugar, fat control: study
Avandia approved for combination with insulin in type 2 diabetes treatment
Avandia Reduces Risk of Progresson from Pre-Diabetes to Type 2 Diabetes by 62 percent
EMEA Statement on Recent Publication on Cardiac Safety of Rosiglitazone (Avandia, Avandamet, Avaglim)
GSK Revises US Labeling for Avandia
Data Affirms Avandia (Rosiglitazone maleate) Cardiovascular Safety Profile
Reaction to Avandia Warnings Stronger Among Internists Than Endocrinologists, According to Study by GfK Market Measures
Texas Family Sues GlaxoSmithKline (GSK) Over Man’s Heart Attack Death Following Avandia Use
To buy AVANDIA click HERE: My Family Drugstore
![[Image]](http://www.myfamilydrugstore.com/img2/Avandia_1.jpg)