Pharmacological interactions of statins
Introduction
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the so-called statins: atorvastatin, cerivastatin,1 fluvastatin, pravastatin, lovastatin, and simvastatin, can achieve relatively large reductions in plasma cholesterol levels and are a well-established class of drugs for the treatment of hypercholesterolemia [1], [2]. It has been widely demonstrated that cholesterol-lowering therapy with statins reduces cardiovascular events and total mortality rates. Overall, the statins are very selective inhibitors of HMG-CoA reductase and do not show any relevant affinity towards other enzymes or receptor systems [3]. In general, statin monotherapy is well tolerated and has a low frequency of adverse events, as documented by their clinical use for more than 15 years. The most important adverse effects, although rare, associated with statins are myopathy, which can progress to rhabdomyolysis, and asymptomatic increase in hepatic transaminases. The effect on hepatic function for the various HMG-CoA reductase inhibitors is roughly dose-related and 1–3% of patients experience an increase in hepatic enzyme levels [2]. The majority of liver abnormalities occur within the first 3 months of therapy and require monitoring. However, since statins are prescribed on a long-term basis, possible interactions with other drugs deserve attention as many patients will typically receive multiple-drug treatment for concomitant conditions during the course of statin therapy. At the pharmacodynamic level, statins are not prone to interference with other drugs [1]. At the pharmacokinetic level, however, interactions can affect the processes by which statins are absorbed, distributed, metabolized, and excreted. Rhabdomyolysis is an uncommon syndrome and occurs in approximately 0.1% of patients who receive statin in monotherapy [4]. However, the incidence of myopathy or rhabdomyolysis is dose-dependent and is increased when HMG-CoA reductase inhibitors are used in combination with agents that share common metabolic pathways [2]. The issue of safety and drug tolerance is particularly important in primary and secondary prevention of cardiovascular disease, where the risks of long-term therapy, together with the co-prescription of other drugs, must be considered in the context of achievable benefits.
Section snippets
Drug interaction with statins
A drug interaction generally occurs when either the pharmacokinetics or pharmacodynamics of one drug is altered by another [5]. Many drug–drug interactions have been demonstrated in clinical experience with statins and in many respects these interactions are qualitatively and quantitatively comparable for all agents of this class. Some of these interactions are indeed of minor clinical consequence because they neither compromise cholesterol-lowering activity nor increase toxicity. Due to
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