Lipid-lowering drugs: are adverse effects predictable and reversible?
Most of the currently available statins and fibric acid derivatives have been implicated in causing complications either in monotherapy or in combination therapy. Adverse events occur more often with the statins that are metabolized via the CYP enzyme system and its 3A4, 2C9 or 2C19 paths. All compounds interfering with the same cytochrome system may either impair or enhance the elimination of statins. Other factors predisposing to adverse effects are age, female sex, renal insufficiency, electrolyte disturbances, infections and trauma. Complications chiefly concern the hepatic function, skeletal muscles and peripheral nerves. The major adverse effect is myopathy, up to rhabdomyolysis with ensuing acute renal insufficiency. Fibrates bind to peroxisome proliferator-activated nuclear receptors alpha, with subsequent stimulation of fatty acid oxidation and reduction in the rate of hepatic lipid generation. Fibrates are associated with a number of adverse effects, including liver enzyme elevations, gastrointestinal side effects and rhabdomyolysis. The combination of statins with fibrates may cause serious complications and should be avoided when possible. In order to prevent or minimize adverse clinical outcomes, patients should be closely monitored and informed of the most common symptoms.
Muscari
Antonio
A
Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Italy. amuscari@med.unibo.it
Puddu
Giovanni M
GM
Puddu
Paolo
P
D001189:Aryl Hydrocarbon Hydroxylases; D001629:Bezafibrate; D008078:Cholesterol, LDL / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004064:Digestive System / Q000187:drug effects; D004359:Drug Therapy, Combination; D015248:Gemfibrozil; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D008099:Liver / Q000201:enzymology; D051437:Renal Insufficiency / Q000139:chemically induced; D012206:Rhabdomyolysis / Q000139:chemically induced; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D015248:Gemfibrozil; D001629:Bezafibrate