AVANDARYL- rosiglitazone maleate and glimepiride tablet, film coated
GlaxoSmithKline LLC
WARNING: CONGESTIVE HEART FAILURE
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Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions ]. After initiation of AVANDARYL? 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 AVANDARYL must be considered.
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AVANDARYL is not recommended in patients with symptomatic heart failure. Initiation of AVANDARYL in patients with established NYHA Class III or IV heart failure is contraindicated
DESCRIPTION
AVANDARYL contains oral antidiabetic drugs used in the management of type diabetes: rosiglitazone maleate and glimepiride. Rosiglitazone maleate is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity.Glimepiride is an oral antidiabetic drug of the sulfonylurea class.
Mechanism of Action
AVANDARYL combines antidiabetic agents with different mechanisms of action to improve glycemic control in patients with type diabetes: Rosiglitazone maleate, member of the thiazolidinedione class, and glimepiride, member of the sulfonylurea class. Thiazolidinediones are insulin-sensitizing agents that act primarily by enhancing peripheral glucose utilization, whereas sulfonylureas act primarily by stimulating release of insulin from functioning pancreatic beta cells
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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AVANDARYL is not recommended in 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 rosiglitazone compared with placebo. Data from long-term clinical trials of rosiglitazone 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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AVANDARYL 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 also 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 (HbA1c) tested. It can take weeks to see reduction in blood glucose and to months to see the full effect of AVANDARYL.
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The risks 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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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 AVANDARYL should immediately report these symptoms to their physician.
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AVANDARYL should be taken with the first meal of the day.
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Therapy with rosiglitazone, 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 AVANDARYL. 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.
AVANDARYL is registered trademark of the GSK group of companies
INDICATIONS AND USAGE
AVANDARYL is 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, rosiglitazone is active only in the presence of endogenous insulin. Therefore, AVANDARYL should not be used in patients with type diabetes or for the treatment of diabetic ketoacidosis.
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Coadministration of AVANDARYL with insulin is not recommended
DOSAGE AND ADMINISTRATION
? Therapy with AVANDARYL should be individualized for each patient. The risk-benefit of initiating monotherapy versus dual therapy with AVANDARYL should be considered.
? No studies have been performed specifically examining the safety and efficacy of AVANDARYL in patients previously treated with other oral hypoglycemic agents and switched to AVANDARYL. Any change in therapy of type diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur. [See Indications and USAge .]
2.1 Starting Dose
The recommended starting dose is mg/1 mg administered once daily with the first meal of the day. For adults already treated with sulfonylurea or rosiglitazone, starting dose of mg/2 mg may be considered.
Maximum Dose
The maximum recommended daily dose is mg rosiglitazone and mg glimepiride.
DOSAGE FORMS AND STRENGTHS
Each rounded triangular tablet contains rosiglitazone maleate and glimepiride as follows:
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4 mg/1 mg yellow, gsk debossed on one side and 4/1 on the other.
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4 mg/2 mg orange, gsk debossed on one side and 4/2 on the other.
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4 mg/4 mg pink, gsk debossed on one side and 4/4 on the other.
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8 mg/2 mg pale pink, gsk debossed on one side and 8/2 on the other.
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8 mg/4 mg red, gsk debossed on one side and 8/4 on the other.
CONTRAINDICATIONS
Initiation of AVANDARYL in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Boxed Warning].
? AVANDARYL is contraindicated in patients with history of hypersensitivity reaction to rosiglitazone or glimepiride or any of the product?s ingredients.
? Patients who have developed an allergic reaction to sulfonamide derivatives may develop an allergic reaction to AVANDARYL. Do not use AVANDARYL in patients who have history of an allergic reaction to sulfonamide derivatives. Reported hypersensitivity reactions include cutaneous eruptions with or without pruritis as well as more serious reactions (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome, dyspnea)
WARNINGS AND PRECAUTIONS
5.1 Cardiac Failure With Rosiglitazone
5.3 Hypoglycemia
5.4 Edema
5.5 Weight Gain
5.6 Hepatic Effects
5.7 Macular Edema
5.8 Fractures
5.9 Hypersensitivity Reactions
5.10 Hematologic Effects
5.11 Hemolytic Anemia
5.12 Increased Risk of Cardiovascular Mortality With Sulfonylureas
5.13 Diabetes and Blood Glucose Control
5.14 Ovulation
Drugs Metabolized by Cytochrome P450
Rosiglitazone: 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 (12.4).]
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the IV, topical, or vaginal preparations of miconazole is not known. Potential interactions of glimepiride with other drugs metabolized by cytochrome P450 2C9 also include phenytoin, diclofenac, ibuprofen, naproxen, and mefenamic acid. [See Clinical Pharmacology (12.4).]
Glimepiride: There may be an interaction between glimepiride and inhibitors (e.g., fluconazole) and inducers (e.g., rifampin) of CYP 2C9. Fluconazole may inhibit the metabolism of glimepiride, causing increased plasma concentrations of glimepiride which may lead to hypoglycemia. Rifampin may induce the metabolism of glimepiride, causing decreased plasma concentrations of glimepiride which may lead to worsening glycemic control.
7.2 Drugs Affecting Glucose Metabolism
A number of medications affect glucose metabolism and may require glimepiride dose adjustment and particularly close monitoring for hypoglycemia or worsening glycemic control
7.3 Miconazole
A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported. Whether this interaction also occurs with other dosage forms of miconazole is not known.
7.4 Concomitant Administration of Colesevelam
Colesevelam can reduce the maximum plasma concentration and total exposure of glimepiride when the two are coadministered. However, absorption is not reduced when glimepiride is administered hours prior to colesevelam. Therefore, AVANDARYL should be administered at least hours prior to colesevelam.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
