Liver enzymes
HMG-CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated
with biochemical abnormalities of liver function. The incidence of persistent elevations (>3
times the upper limit of normal [ULN] occurring on 2 or more consecutive occasions) in serum
transaminases in fixed dose studies was 0.4, 0, 0, and 0.1% in patients who received rosuvastatin
5, 10, 20, and 40 mg, respectively. In most cases, the elevations were transient and resolved or
improved on continued therapy or after a brief interruption in therapy. There were two cases of
jaundice, for which a relationship to rosuvastatin therapy could not be determined, which
resolved after discontinuation of therapy. There were no cases of liver failure or irreversible liver
disease in these trials.
It is recommended that liver function tests be performed before and at 12 weeks following
both the initiation of therapy and any elevation of dose, and periodically (e.g.,
semiannually) thereafter. Liver enzyme changes generally occur in the first 3 months of
treatment with rosuvastatin. Patients who develop increased transaminase levels should be
monitored until the abnormalities have resolved. Should an increase in ALT or AST of >3 times
ULN persist, reduction of dose or withdrawal of rosuvastatin is recommended.
Rosuvastatin should be used with caution in patients who consume substantial quantities of
alcohol and/or have a history of liver disease (see CLINICAL PHARMACOLOGY, Special
Populations, Hepatic Insufficiency). Active liver disease or unexplained persistent transaminase
elevations are contraindications to the use of rosuvastatin (see CONTRAINDICATIONS).