Issue 136 Item 11 Liver Function Testing Crucial with Thiazolidinediones, New Gu

Testing frequency might be safely modified or reduced based on the particular drug prescribed and trends in (ALT) levels. Preliminary results of a study were presented December 11th at the clinical meeting of the American Society of Health-System Pharmacists.

Frequent liver function monitoring is recommended for patients taking thiazolidinediones, the drugs used as monotherapy or in combination with other medications in treatment of type II diabetes. Recently updated guidelines from the American Association of Clinical Endocrinologists (AACE) call for monitoring liver function every two months for the first year of treatment with thiazolidinediones-and periodically thereafter-because of the high risk of hepatocellular injury.

Researchers at the Central Alabama Veterans Health Care System (CAVHCS) in Montgomery, Alabama, United States, are conducting an ongoing study to determine whether liver function in patients taking one of commonly prescribed thiazolidinediones, rosiglitazone (Avansia) and pioglitazone (Actos), is appropriately monitored. The AACE recommends that rosiglitazone be discontinued if ALT levels exceed three times the upper limit of normal on two samples, and that pioglitazone be discontinued if ATL exceeds 2.5 times the upper limit of normal.

A total of 53 patients, with a mean age of 67 and predominantly male, were evaluated in a retrospective, randomised, observational analysis. The researchers sought to determine whether the patients were being monitored appropriately and whether significant ALT increases prompted discontinuation of the medication. The results were based on the monitoring activities during the first year following initiation of treatment.

The researchers found that although ALT values declined steadily over the course of the first year of treatment, indicating efficacy of treatment and no need to discontinue the medications, patients’ liver function was not being monitored according to AACE guidelines. The average time between liver checks, after baseline, ranged from 84 days to 157 days, and six patients were monitored only at baseline.

However, the researchers noted that the average ALT values in the study group (from 21 at first check to 19 at third check) might indicate that rosiglitazone and pioglitazone do not require the liver monitoring frequency required by an earlier thiazolidinedione, troglitazone (Rezulin), which was voluntarily removed from the market in 2000 because of the high incidence of liver injury.