Parke-Davis, United States of America. The manufacturer of the diabetes drug, troglitazone (Rezulin: Parke Davis), has strengthened the requirements for liver enzyme monitoring in order to reduce the risk of rare but serious liver injury, including liver failure leading to transplant or death, that has been reported in association with this product.
Patients with moderately elevated alanine aminotransferase (ALT) levels at the start of therapy (greater than 1.5 times the upper limit of normal) should not be initiated on troglitazone therapy.
ALT levels should be measured at the start of troglitazone therapy and monthly for eight months, then every two months for the remainder of the first year of therapy and periodically thereafter.
Patients whose ALT levels are found to be moderately elevated (greater than 1.5-2 times the upper limit of normal) during troglitazone therapy should have ALT levels retested within a week then weekly until they either return to normal levels or rise to about 3 times the upper limit of normal, at which point troglitazone should be discontinued.
For patients not responding to 400 mg, the troglitazone dose should be increased to 600 mg after one month. For patients not responding adequately to 600 mg after one month, troglitazone should be discontinued and alternative therapeutic options should be pursued.
Since liver enzyme monitoring recommendations were originally implemented in November 1997, there have been few new cases of severe hepatocellular events and these primarily involved patients who may not have been monitored as recommended in the labelling.
[See also DRS Information Exchange System Alert No. 66 dated 7 November 1997 and Alert No. 67 dated 4 December 1997]
Reference: Letter to Healthcare Professionals, Parke- Davis, 28 July 1998.