Actos - Warnings & Precautions

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Pioglitazone is structurally related to troglitazone, a thiazolidinedione no longer marketed in the United States, which was associated with idiosyncratic hepatotoxicity and rare cases of liver failure, liver transplants and death during postmarketing clinical use.

Pending the availability of the results of additional large, long-term controlled clinical trials and additional postmarketing safety data, it is recommended that patients treated with ACTOS undergo periodic monitoring of liver enzymes. Serum ALT (alanine aminotransferase) levels should be evaluated prior to the initiation of therapy with ACTOS in all patients, every two months for the first year of therapy, and periodically thereafter. Liver function tests should also be obtained for patients if symptoms suggestive of hepatic dysfunction occur, e. g., nausea, vomiting, abdominal pain, fatigue, anorexia or dark urine. The decision whether to continue the patient on therapy with ACTOS should be guided by clinical judgement pending laboratory evaluations. If jaundice is observed, drug therapy should be discontinued.

Therapy with ACTOS should not be initiated if the patient exhibits clinical evidence of active liver disease or the ALT levels exceed 2.5 times the upper limit of normal. Patients with mildly elevated liver enzymes (ALT levels at 1 to 2.5 times the upper limit of normal) at baseline or any time during therapy with ACTOS should be evaluated to determine the cause of the liver enzyme elevation. Initiation or continuation of therapy with ACTOS in patients with mildly elevated liver enzymes should proceed with caution and include appro-priate clinical follow-up which may include more frequent liver enzyme monitoring.

If serum transaminase levels are increased (ALT > 2.5 times the upper limit of normal), liver function tests should be evaluated more frequently until the levels return to normal or pretreatment values. If ALT levels exceed 3 times the upper limit of normal, the test should be repeated as soon as possible. If ALT levels remain > 3 times the upper limit of normal or if the patient is jaundiced, ACTOS therapy should be discontinued. There are no data available to evaluate the safety of ACTOS in patients who experi-enced liver abnormalities, hepatic dysfunction, or jaundice while on troglitazone.

ACTOS should not be used in patients who experienced jaundice while taking troglitazone. Laboratory Tests FBG and HbA1c measurements should be performed periodically to monitor glycemic con-trol and the therapeutic response to ACTOS. Liver enzyme monitoring is recommended prior to initiation of therapy with ACTOS in all patients and periodically thereafter (see PRECAUTIONS, General, Hepatic Effects and ADVERSE REACTIONS, Serum Transaminase Levels).