AVANDIA- rosiglitazone maleate tablet, film coated
AVANDIA 2MG- rosiglitazone maleate tablet, film coated
AVANDIA 4MG- rosiglitazone maleate tablet, film coated
AVANDIA 8MG- rosiglitazone maleate tablet, film coated
GlaxoSmithKline LLC
WARNING: CONGESTIVE HEART FAILURE
? Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions ]. After initiation of AVANDIA , and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of AVANDIA must be considered.
? AVANDIA is not recommended in patients with symptomatic heart failure. Initiation of AVANDIA in patients with established NYHA Class III or IV heart failure is contraindicated. [See Contraindications , Warnings and Precautions .]
DESCRIPTION
AVANDIA (rosiglitazone maleate) is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. AVANDIA 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.
Mechanism of Action
Rosiglitazone, member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. Rosiglitazone is highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPAR?). In humans, PPAR receptors are found in key target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR? nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In addition, PPAR?-responsive genes also participate in the regulation of fatty acid metabolism.
INDICATIONS AND USAGE
AVANDIA is thiazolidinedione antidiabetic agent indicated as an adjunct to diet and exercise to improve glycemic control in adults with type diabetes mellitus.
Important Limitations of Use:
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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 diabetes mellitus or for the treatment of diabetic ketoacidosis.
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The coadministration of AVANDIA and insulin is not recommended
DOSAGE AND ADMINISTRATION
AVANDIA may be administered at starting dose of mg either as single daily dose or in divided doses. For patients who respond inadequately following to 12 weeks of treatment, as determined by reduction in fasting plasma glucose (FPG), the dose may be increased to mg daily. Increases in the dose of AVANDIA should be accompanied by careful monitoring for adverse events related to fluid retention [see Boxed Warning, Warnings and Precautions ]. AVANDIA may be taken with or without food.
The total daily dose of AVANDIA should not exceed mg.
Patients receiving AVANDIA in combination with other hypoglycemic agents may be at risk for hypoglycemia, and reduction in the dose of the concomitant agent may be necessary.
2.1 Specific Patient Populations
Renal Impairment: No dosage adjustment is necessary when AVANDIA is used as monotherapy in patients with renal impairment. Since metformin is contraindicated in such patients, concomitant administration of metformin and AVANDIA is also contraindicated in patients with renal impairment.
Hepatic Impairment: Liver enzymes should be measured prior to initiating treatment with AVANDIA. Therapy with AVANDIA 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, liver enzymes should be monitored periodically per the clinical judgment of the healthcare professional. [See Warnings and Precautions , Clinical Pharmacology (12.3).]
Pediatric: Data are insufficient to recommend pediatric use of AVANDIA
DOSAGE FORMS AND STRENGTHS
Pentagonal film-coated TILTAB? tablet contains rosiglitazone as the maleate as follows:
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2 mg pink, debossed with GSK on one side and on the other
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4 mg orange, debossed with GSK on one side and on the other
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8 mg red-brown, debossed with GSK on one side and on the other
CONTRAINDICATIONS
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Initiation of AVANDIA in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Boxed Warning].
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Use in patients with history of hypersensitivity reaction to rosiglitazone or any of the product?s ingredients.
ADVERSE REACTIONS
The following adverse reactions are discussed in more detail elsewhere in the labeling:
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Cardiac Failure
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Major Adverse Cardiovascular Events
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Edema
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Weight Gain
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Hepatic Effects
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Macular Edema
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Fractures
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Hematologic Effects
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Ovulation
DRUG INTERACTIONS
7.1 CYP2C8 Inhibitors and Inducers
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. [See Clinical Pharmacology
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C.
PATIENT COUNSELING info.
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
There are multiple medications available to treat type diabetes. The benefits and risks of each available diabetes medication should be taken into account when choosing particular diabetes medication for given patient.
Patients should be informed of the following:
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AVANDIA is not recommended for patients with symptomatic heart failure.
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A meta-analysis of mostly short-term trials suggested an increased risk for myocardial infarction with AVANDIA compared with placebo. Data from long-term clinical trials of AVANDIA versus other antidiabetes agents (metformin or sulfonylureas), including cardiovascular outcome trial (RECORD), observed no difference in overall mortality or in major adverse cardiovascular events (MACE) and its components.
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AVANDIA is not recommended for patients who are taking insulin.
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Management of type diabetes should include diet control. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient because they help improve insulin sensitivity. This is important not only in the primary treatment of type diabetes, but in maintaining the efficacy of drug therapy.
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It is important to adhere to dietary instructions and to regularly have blood glucose and glycosylated hemoglobin tested. It can take weeks to see reduction in blood glucose and to months to see the full effect of AVANDIA.
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Blood will be drawn to check their liver function prior to the start of therapy and periodically thereafter per the clinical judgment of the healthcare professional. Patients with unexplained symptoms of nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine should immediately report these symptoms to their physician.
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Patients who experience an unusually rapid increase in weight or edema or who develop shortness of breath or other symptoms of heart failure while on AVANDIA should immediately report these symptoms to their physician.
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AVANDIA can be taken with or without meals.
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When using AVANDIA in combination with other hypoglycemic agents, the risk of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and their family members.
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Therapy with AVANDIA, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. As 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 trials so the frequency of this occurrence is not known.
AVANDIA and TILTAB are registered trademarks of the GSK group of companies.
