Long-term safety and efficacy profile of simvastatin.
Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions. Approximately 10% of this population received simvastatin for a period of greater than or equal to 2 years. The population on whom this safety analysis is based had a mean age of 50 years; 62% were men and approximately 27% had preexisting coronary artery disease. Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56% of the study population (last recorded dose). The most frequently reported drug-related clinical adverse experiences were constipation (2.5%), abdominal pain (2.2%), flatulence (2.0%) and headaches (1%). Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1% of this cohort with only 0.1% of the total population requiring discontinuation of therapy. There were no clinically apparent episodes of hepatitis. Discontinuation of therapy due to myopathy was extremely rare (0.08%). Only minimal increases in the frequency of lens opacities (1%) were observed from baseline to the last lens examination during follow-up, consistent with the expected increase in lens opacity development due to normal aging. Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population.(ABSTRACT TRUNCATED AT 250 WORDS)
Boccuzzi
S J
SJ
Merck Sharp & Dohme Research Laboratories, Merck & Co. Inc., Rahway, New Jersey 07065-0914.
Bocanegra
T S
TS
Walker
J F
JF
Shapiro
D R
DR
Keegan
M E
ME
D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002386:Cataract / Q000139:chemically induced; D003327:Coronary Disease / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D019821:Simvastatin
D000924:Anticholesteremic Agents; D008148:Lovastatin; D019821:Simvastatin