Trade Names:Avandia- Tablets 2 mg- Tablets 4 mg- Tablets 8 mg
Increases insulin sensitivity in liver, muscle, and adipose tissue.
Bioavailability is 99%. T max is 1 h. When administered with food, C max is lowered 28%, with a delay in T max by 1.75 h. Administration with food does not affect the AUC, but the C max may be decreased by approximately 28% and the T max delayed by 1.75 h. However, rosiglitazone may be taken without regard to meals.
Vd is about 17.6 L. Protein binding is 99.8%, primarily to albumin.
Extensively metabolized by isoenzyme CYP2C8, with CYP2C9 as minor pathway.
Eliminated in urine (64%) and feces (23%). Plasma half-life is 103 to 158 h. Elimination half-life is 3 to 4 h.
No dosage adjustments are needed.Hepatic Function Impairment
In moderate to severe liver disease (Child-Pugh class B/C), unbound oral Cl was significantly lower, C max and AUC were increased 2- and 3-fold, respectively, and elimination half-life was about 2 h longer.Children
Pharmacokinetic parameters studied in children were consistent with parameter estimates in adult patients.Gender
Mean oral Cl in women was about 6% lower.Race
Race does not affect pharmacokinetics.
Improved glycemic control of type 2 diabetes mellitus as monotherapy and as an adjunct to diet and exercise.
Increased ovulation frequency in women with polycystic ovary syndrome; reduced in-stent restenosis in patients with diabetes.
Established New York Heart Association class III or IV heart failure; hypersensitivity to any component of the product.
Individualize therapy.Combination TherapyMetformin Adults
PO In combination with metformin, initiate therapy with rosiglitazone 4 mg as a single dose or 2 divided doses. Following 8 to 12 weeks of treatment, dosage may be increased to 8 mg daily if needed.Sulfonylureas Adults
PO In combination with sulfonylureas, the recommended dose of rosiglitazone is 4 mg as a single dose or 2 divided doses. Following 8 to 12 weeks of treatment, dosage may be increased to 8 mg daily if needed. If patient reports hypoglycemia, decrease the sulfonylurea dose.Sulfonylurea and Metformin Adults
PO In combination with a sulfonylurea and metformin, initiate therapy with rosiglitazone 4 mg as a single dose or 2 divided doses. Following 8 to 12 wk of treatment, dosage may be increased to 8 mg daily if needed. If patient develops hypoglycemia, decrease the sulfonylurea dose.Hepatic Function ImpairmentAdults
PO Treatment should not be initiated in patients exhibiting evidence of active liver disease or increased serum transaminase levels (ALT more than 2.5 × ULN at the start of therapy).MonotherapyAdults
PO Initiate therapy at 4 mg/day, administered as a single dose or 2 divided doses. For patients who respond inadequately following 8 to 12 wk of treatment, the dosage may be increased to 8 mg daily.
Store at 59° to 86°F. Dispense in light-resistent containers.
May decrease rosiglitazone AUC; changes in diabetes treatment may be needed when the CYP2C8 inducer is started or stopped.CYP2C8 inhibitors (eg, azole antifungal agents [ketoconazole], fluvoxamine, gemfibrozil, trimethoprim)
May elevate rosiglitazone plasma levels, increasing the pharmacologic effects and adverse reactions.Insulin
Risk of edema may be increased, even after several months of therapy. Increased risk of CHF and MI.Nitrates
Increased risk of myocardial ischemia.
None well documented.
Hypertension (4%); CHF (postmarketing).
Headache (6%); fatigue (4%).
Pruritus, rash, Stevens-Johnson syndrome, urticaria (postmarketing)
Nasopharyngitis (6%); sinusitis (3%); macular edema (postmarketing).
Anemia (2%); decreased WBC, dose-related decreases in Hgb and Hct.
Hepatic enzyme elevation 3 or more × ULN; hepatitis (postmarketing).
Decrease in free fatty acids; increase in HDL, LDL, and total cholesterol.
Hyperglycemia (4%); hypoglycemia (3%).
Bone fractures (9%); arthralgia, back pain (5%).
Upper respiratory tract infection (10%); pleural effusion, pulmonary edema (postmarketing).
Injury (8%); edema (5%); anaphylactic reactions, angioedema (postmarketing).
May occur or be exacerbated. Observe patients for signs and symptoms of heart failure after starting therapy or increasing the dose. Manage heart failure according to current standards of care. Consider discontinuation or dose reduction. Use of drug is not recommended in patients with symptomatic heart failure.Myocardial ischemia
Risk of myocardial ischemia events (eg, angina, MI) may be increased; however, data are inconclusive.
Monitor for signs and symptoms of heart failure. Obtain periodic fasting blood glucose and HbA 1c concentrations to monitor therapeutic response. Assess liver enzymes prior to initiation of therapy and periodically thereafter.
Category C .
Safety and efficacy not established.
No dosage adjustments are needed.
Use with caution. Do not initiate therapy in patients with clinical evidence of active liver disease or baseline ALT more than 2.5 × ULN. Discontinue therapy if ALT increases to more than 3 × ULN and persists.
Increased incidence of bone fractures noted in women, but not in men.
Use with caution; can cause fluid retention.
Decreases in Hgb (1 g/dL or less) and Hct (3.3% or less) have been reported; may be related to dose-related increases in plasma volume associated with rosiglitazone therapy.
May increase risk of hypoglycemia when used in combination with other hypoglycemic agents; may need dose reduction of concomitant agent.
Has been reported in postmarketing experience.
May result in resumption of ovulation in premenopausal anovulatory women.
Dose-related weight gain has been seen alone and in combination with other hypoglycemic agents. Unusually rapid increases in weight may be caused by fluid accumulation; assess such patients for fluid accumulation and volume-related events.
Limited data are available.
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