Rosuvastatin-Associated Adverse Effects and Drug-Drug Interactions in the Clinical Setting of Dyslipidemia

Abstract

HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with an...

Beta-glucan- or rice bran-enriched foods: a comparative crossover clinical trial on lipidic pattern in mildly hypercholesterolemic men

“…The use of statins, the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that are the mainstay in the pharmacological management of dyslipidemia, has been reserved in patients with at least one other risk of CVD. Moreover, the unwanted side effects of statins are numerous, frequent and dangerous (Kostapanos et al, 2010). On the contrary, the consumption of foods enriched in beta-glucans has no known side effects, and, moreover, permits a higher intake per serving with a minimum decrease in palatability (Jenkins et al, 2002).…”

Statins and gastrointestinal cancers

“…A CORONA tanulmány eredményei szerint napi 10 mg rosuvastatin nem okozott általános tumorincidenciacsökkenést a placebóval kezelt csoporthoz képest 32,8 hónap átlagos követési idő mellett. A JUPITER vizsgálat sem mutatott ki 10 mg-os rosuvastatindózis kapcsán eltérő előfordulást a daganatos betegségek vonatkozásá-ban a placebóhoz képest, 20 mg-os dózisnál azonban szignifi kánsan kevesebben haltak meg rákos megbetegedés miatt, mint a placebót kapó csoportban [50].…”

Therapeutic options for statin-intolerant patients

“…Most frequent statin-specific adverse events include musculoskeletal symptoms (e.g., myalgia or muscle weakness) as well as asymptomatic elevations of the plasma activities of creatine kinase (CK) and liver enzymes [aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)] [1][2][3] . Myalgia and elevation of transaminases activities may account for two-thirds of statin-related adverse effects in clinical trials 3 .…”

“…Myalgia and elevation of transaminases activities may account for two-thirds of statin-related adverse effects in clinical trials 3 . Furthermore, central nervous system (e.g., headache or dizziness) and gastrointestinal tract (e.g., nausea or diarrhoea) symptoms are commonly reported by statin-treated patients [1][2][3] . Severe adverse events of statins include myositis, rhabdomyolysis, as well as a clinically relevant rise in AST and/or ALT activity 1,2 .…”

“…Furthermore, central nervous system (e.g., headache or dizziness) and gastrointestinal tract (e.g., nausea or diarrhoea) symptoms are commonly reported by statin-treated patients [1][2][3] . Severe adverse events of statins include myositis, rhabdomyolysis, as well as a clinically relevant rise in AST and/or ALT activity 1,2 . Moderate elevations in serum CK activity during statin treatment are common but often not associated with myalgia or myositis 2 .…”