Actos Side Effects & Drug Interactions

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Actos - Side Effects & Drug Interactions [Pioglitazone]

Serum Transaminase Levels:

During placebo-controlled clinical trials in the U. S., a total of 4 of 1526 (0.26%) patients treated with ACTOS and 2 of 793 (0.25%) placebo-treated patients had ALT values 3 times the upper limit of normal. During all clinical studies in the U. S., 11 of 2561 (0.43%) patients treated with ACTOS had ALT values 3 times the upper limit of normal. All patients with follow-up values had reversible elevations in ALT. In the population of patients treated with ACTOS, mean values for bilirubin, AST, ALT, alkaline phosphatase, and GGT were decreased at the final visit compared with baseline. Fewer than 0.12% of patients treated with ACTOS were withdrawn from clinical trials in the U. S. due to abnormal liver function tests. In pre-approval clinical trials, there were no cases of idiosyncratic drug reactions lead-ing to hepatic failure (see PRECAUTIONS, Hepatic Effects).

CPK Levels:

During required laboratory testing in clinical trials, sporadic, transient eleva-tions in creatine phosphokinase levels (CPK) were observed. A single, isolated elevation to greater than 10 times the upper limit of normal (values of 2150 to 8610) was noted in 7 patients. Five of these patients continued to receive ACTOS and the other two patients had completed receiving study medication at the time of the elevated value. These elevations resolved without any apparent clinical sequelae. The relationship of these events to ACTOS therapy is unknown.

Drug Interactions

Oral Contraceptives:

Administration of another thiazolidinedione with an oral contraceptive containing ethinyl estradiol and norethindrone reduced the plasma concentrations of both hormones by approximately 30%, which could result in loss of contraception. The pharma-cokinetics of coadministration of ACTOS and oral contraceptives have not been evaluated in patients receiving ACTOS and an oral contraceptive. Therefore, additional caution regarding contraception should be exercised in patients receiving ACTOS and an oral contraceptive. In vivo drug-drug interaction studies have suggested that pioglitazone may be a weak inducer of CYP 450 isoform 3A4 substrate (see CLINICAL PHARMACOLOGY, Metabolism and Drug-Drug Interactions).