Skeletal muscle
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria
have been reported with pravastatin and other drugs in this class. Uncomplicated
myalgia has also been reported in pravastatin-treated patients (see ADVERSE
REACTIONS). Myopathy, defined as muscle aching or muscle weakness in conjunction
with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper
normal limit, was rare (<0.1%) in pravastatin clinical trials. Myopathy should be
considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or
marked elevation of CPK. Patients should be advised to report promptly unexplained
muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Pravastatin therapy should be discontinued if markedly elevated CPK levels occur
or myopathy is diagnosed or suspected. Pravastatin therapy should also be
temporarily withheld in any patient experiencing an acute or serious condition
predisposing to the development of renal failure secondary to rhabdomyolysis, e.g.,
sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or
electrolyte disorders; or uncontrolled epilepsy.
The risk of myopathy during treatment with another HMG-CoA reductase inhibitor is
increased with concurrent therapy with either erythromycin, cyclosporine, niacin, or
fibrates. However, neither myopathy nor significant increases in CPK levels have been
observed in three reports involving a total of 100 post-transplant patients (24 renal and 76
cardiac) treated for up to two years concurrently with pravastatin 10-40 mg and
cyclosporine. Some of these patients also received other concomitant immunosuppressive
therapies. Further, in clinical trials involving small numbers of patients who were treated
concurrently with pravastatin and niacin, there were no reports of myopathy. Also,
myopathy was not reported in a trial of combination pravastatin (40 mg/day) and
gemfibrozil (1200 mg/day), although 4 of 75 patients on the combination showed marked
CPK elevations versus one of 73 patients receiving placebo. There was a trend toward
more frequent CPK elevations and patient withdrawals due to musculoskeletal symptoms
in the group receiving combined treatment as compared with the groups receiving
placebo, gemfibrozil, or pravastatin monotherapy (see PRECAUTIONS: Drug
Interactions). The use of fibrates alone may occasionally be associated with
myopathy. The combined use of pravastatin and fibrates should be avoided unless
the benefit of further alterations in lipid levels is likely to outweigh the increased
risk of this drug combination.
Pravachol
Cholesterol
Liver enzymes
Drug interactions
Dosage and administration
Pharmacokinetics metabolism
Skeletal muscle
Clinical pharmacology