|Drug Name:||PRAVASTATIN SODIUM|
|Manufacturer:||Watson Laboratories, Inc.|
|Other Info:||Manufactured for:Watson Laboratories, Inc.Corona, CA 92880 USAManufactured by:Bristol-Myers Squibb CompanyPrinceton, NJ 08543 USA1200044A1Revised: June 2007|
Hypersensitivity to any component of this medication.Active liver disease or unexplained, persistent elevations of serum transaminases (see WARNINGS).Pregnancy and Lactation.
Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Cholesterol and other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Since HMG-CoA reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, they are contraindicated during pregnancy and in nursing mothers.
Pravastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.If the patient becomes pregnant while taking this class of drug, therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus (see PRECAUTIONS: Pregnancy).
HMG-CoA reductase inhibitors, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function.
In three long-term (4.8-5.9 years), placebo-controlled clinical trials (WOS, LIPID, CARE; see CLINICAL PHARMACOLOGY: Clinical Studies), 19,592 subjects (19,768 randomized), were exposed to pravastatin or placebo.
In an analysis of serum transaminase values (ALT, AST), incidences of marked abnormalities were compared between the pravastatin and placebo treatment groups; a marked abnormality was defined as a post-treatment test value greater than three times the upper limit of normal for subjects with pretreatment values less than or equal to the upper limit of normal, or four times the pretreatment value for subjects with pretreatment values greater than the upper limit of normal but less than 1.5 times the upper limit of normal.
Marked abnormalities of ALT or AST occurred with similar low frequency (?1.2%) in both treatment groups.
Overall, clinical trial experience showed that liver function test abnormalities observed during pravastatin therapy were usually asymptomatic, not associated with cholestasis, and did not appear to be related to treatment duration.
In a 320-patient placebo-controlled clinical trial, subjects with chronic (>6 months) stable liver disease, due primarily to hepatitis C or non-alcoholic fatty liver disease, were treated with 80 mg pravastatin or placebo for up to 9 months.
The primary safety endpoint was the proportion of subjects with at least one ALT ?2 times the upper limit of normal for those with normal ALT (? the upper limit of normal) at baseline or a doubling of the baseline ALT for those with elevated ALT (> the upper limit of normal) at baseline.
By Week 36, 12 out of 160 (7.5%) subjects treated with pravastatin met the prespecified safety ALT endpoint compared to 20 out of 160 (12.5%) subjects receiving placebo.
Conclusions regarding liver safety are limited since the study was not large enough to establish similarity between groups (with 95% confidence) in the rates of ALT elevation.It is recommended that liver function tests be performed prior to the initiation of therapy and when clinically indicated.Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of pravastatin (see CONTRAINDICATIONS). Caution should be exercised when pravastatin is administered to patients who have a recent (<6 months) history of liver disease, have signs that may suggest liver disease (e.g., unexplained aminotransferase elevations, jaundice), or are heavy users of alcohol (see CLINICAL PHARMACOLOGY: Pharmacokinetics/Metabolism).
Such patients should be closely monitored, started at the lower end of the recommended dosing range (see DOSAGE AND ADMINISTRATION: Adult Patients), and titrated to the desired therapeutic effect.Patients who develop increased transaminase levels or signs and symptoms of active liver disease while taking pravastatin should be evaluated with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return to normal.Should an increase in AST or ALT of three times the upper limit of normal or greater persist, withdrawal of pravastatin therapy is recommended.