Avandia - Clinical Pharmacology

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Special Populations

Age: Results of the population pharmacokinetic analysis (n = 716 <65 years; n = 331 65 years) showed that age does not significantly affect the pharmacokinetics of rosiglitazone.

Gender

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 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 PPAR is expressed in adipose tissues, this differentiating characteristic may account, at least in part, for the greater response to AVANDIA in females. Since therapy should be individualized, no dose adjustments are necessary based on gender alone.

Hepatic Impairment

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 Cmax and AUC0-inf 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 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 baseline (see PRECAUTIONS, General, Hepatic Effects).

Renal Impairment

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. Since metformin is contraindicated in patients