Lovastatin was compared to placebo in 8245 patients with hypercholesterolemia (total cholesterol 6.2 – 7.8mmol/L) in a randomized, double-blind, parallel, 48-week expanded clinical evaluation of lovastatin (EXCEL study). Clinical adverse reactions reported as possibly, probably or definitely drug-related in any treatment group is shown in the table as follows. (See table.)
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Other clinical adverse reactions reported as possibly, probably or definitely drug-related in 0.5 to 1.0% of patients in any drug-related group are listed as follows. In all these cases, the incidence on drug and placebo was not statistically significant.
Body as a whole:
acid regurgitation, dry mouth, vomiting.
leg pain, shoulder pain, arthralgia.
No significant difference was found among the different treatment groups including placebo in the incidence of serious clinical adverse experiences including death due to CHD, non-fatal myocardial infarction, cancer, and deaths due to all causes. This study was not designed or powered to evaluate the incidence of these serious clinical adverse experiences. The EXCEL study included a minority of patients at risk of or with coronary artery disease; however, its findings cannot be extrapolated in this respect to other segments of the high-risk population.
Marked persistent increases of serum transaminases have been noted.
Other liver function test abnormalities including elevated phosphatase and bilirubin have been reported. In the EXCEL study, 7.3% of the patients on lovastatin had elevations of CPK levels of at least twice the normal value on one or more occasions compared to 6.2% on placebo.
The EXCEL study, however, excluded patients with factors known to be associated with an increased risk of myopathy.
Visual evoked response, nerve conduction measurements and electromyography in 30 patients showed no evidence of neurotoxic effects of lovastatin.
Effect on the Lens:
Current long-term data from clinical trials do not indicate an adverse effect of lovastatin on the human lens.
Post Marketing Experience:
The following additional side effects have been reported since lovasatin was marketed: hepatitis, cholestatic jaundice, vomiting, anorexia, paresthesia and psychic disturbances including anxiety, erythema multiform, including Stevens-John syndrome; toxic epidermal necrolysis.
An apparent hypersensitivity syndrome has been reported rarely which has included one or more of the following features: anaphylaxis, angioedema, lupus-like syndrome, polymyalgia, rheumatica, vasculities, thrombocytopenia, leucopenia, eosinophilia, hemolytic anemia, positive ANA, ESR increase, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, flushing, chills, dyspnea and malaise.
There have been rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally non-serious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Increases in HbA1c and fasting serum glucose level have been reported with statins.