Ezetimibe-associated adverse effects: what the clinician needs to know

Florentin, Matilda; Liberopoulos, Evangelos N.; Elisaf, Moses

doi:10.1111/j.1742-1241.2007.01592.x

Cited by 65 publications

(47 citation statements)

References 85 publications

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“…Combination treatment was well-tolerated (three withdrawals) 30 . These findings are in accordance with most studies showing that ezetimibe, alone or in combination with statins, was not associated with increased rates of myopathy or rhabdomyolysis 31 . A meta-analysis of randomized controlled trials, which involved 5039 patients, assessed the efficacy and safety of adding ezetimibe 10 mg/day to ongoing statin treatment 32 .…”

Section: Efficacysupporting

confidence: 82%

Therapeutic options for statin-intolerant patients

Kostapanos

Athyros

Karagiannis

et al. 2012

Current Medical Research and Opinion

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Section: Efficacysupporting

confidence: 82%

Therapeutic options for statin-intolerant patients

Kostapanos

Athyros

Karagiannis

et al. 2012

Current Medical Research and Opinion

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“…(42) The FDC of atorvastatin plus ezetimibe in our study was well-tolerated, with a safety profile comparable to that of atorvastatin monotherapy. Mild dyspepsia was the only adverse event encountered in this study.…”

Section: Discussionmentioning

confidence: 78%

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

Padhy¹,

Yadav²,

Gupta³

2013

SMedJ

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ResUlTsOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference −14.4 ± 6.5, 95% confidence interval [CI] −1.0 to −27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference −19.9 ± 6.1, 95% CI −7.4 to −32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.CONClUsION Combination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and antiinflammatory efficacy than atorvastatin monotherapy. Keywords: atorvastatin, ezetimibe, high sensitivity C-reactive protein, intercellular cell adhesion moleculeSingapore Med J 2013; 54(2): 90-95

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“…Deficiency of acid SMase in hepatic cells may increase the risk of inflammation and proliferation, due to the resistance to apoptosis. Although ezetimibe is considered as a safe drug, case reports recently showed that it may induce liver swelling, hepatitis, and abnormal changes in liver enzymes [34][35][36][37]. How the reduction of acid SMase by ezetimibe may be involved in these phenomena is unknown.…”

Section: Discussionmentioning

confidence: 99%

Ezetimibe Inhibits Expression of Acid Sphingomyelinase in Liver and Intestine

Cheng

Liu

et al. 2009

Lipids

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Ezetimibe inhibits cholesterol absorption in the intestine. Sphingomyelin has strong interactions with cholesterol. We investigated the effects of ezetimibe on Sphingomyelinase (SMase) expression in intestine and liver. After feeding rats with ezetimibe (5 mg/kg per day) for 14 days, acid SMase activities in the liver and in the proximal part of small intestine were reduced by 34 and 25%, respectively. Alkaline SMase (alk-SMase) was increased in the proximal part of the small intestine. Administration of lower doses of ezetimibe reduced acid SMase only in the liver by 14% (P < 0.05). In cell culture studies, ezetimibe decreased acid SMase activity in Hep G2 and Caco-2 cells dose-dependently. The reductions were more rapid for Hep G2 cells than for Caco-2 cells. Western blot showed that acid SMase protein was decreased in both Hep G2 and Caco-2 cells by 100 microM ezetimibe. The SM content was increased in Hep G2 cells but not Caco-2 cells, and total cholesterol content was increased in both cell lines 24 h after stimulation with 100 microM ezetimibe. Mevastatin, the inhibitor of cholesterol synthesis, induced a mild increase in acid SMase activity in Hep G2 cells but not Caco-2 cells. Following the reduction of acid SMase, ezetimibe at high dose slightly increased alk-SMase activity. In conclusion, the study demonstrates an inhibitory effect of ezetimibe on acid SMase activity and expression in both liver and intestine.

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Ezetimibe-associated adverse effects: what the clinician needs to know

Cited by 65 publications

References 85 publications

Therapeutic options for statin-intolerant patients

Therapeutic options for statin-intolerant patients

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

Ezetimibe Inhibits Expression of Acid Sphingomyelinase in Liver and Intestine

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