Recurrence and Severe Worsening of Hepatotoxicity After Reintroduction of Atorvastatin in Combination With Ezetimibe

Abstract

Severe hepatotoxicity is a rare but well-known adverse reaction to statins. However, despite the widespread use of statins, only a few cases describing statin reexposure or switch to another statin after liver injury have been published. The literature on hepatotoxicity with ezetimibe alone or in combination with statins is also scarce. We report a case where a patient with a history of elevated liver enzymes while using atorvastatin, but prior and subsequent good tolerance to simvastatin and pravastatin, developed drug-induced liver injury on reexposure to a combination of atorvastatin and ezetimibe. The hepatotoxicity in our patient was most likely caused by reexposure to atorvastatin, although we cannot exclude ezetimibe as a contributing factor. This case highlights the risk of hepatotoxicity recurrence on rechallenge with the same statin. The tolerance to other statins in this case also strengthens the suspicion that statin-induced liver injury may not be a class effect, although the current data are too scarce to draw any definite conclusions.

Autoimmune-like Drug-induced Liver Injury Caused by Fenofibrate, Atorvastatin, and Ezetimibe: A Case Report and Literature Review

“…There is no reason to doubt the cross sensitivity of ezetimibe to liver injury with other cholesterol lowering drugs. Compared with statin therapy, severe side effects are very rare, particularly when the drug is used as monotherapy in patients with statin intolerance [26].In fact,a lot of previous published cases of ezetimibe-induced liver injury have been reported in combination with a statin [27][28][29]. Reports of severe acute liver injury caused by the sole use of Ezetimibe are very rare.…”

Механизмы Гепатотоксического Действия Лекарственных Средств

“…Ýòè èññëåäîâàíèÿ ÿâíî ïîäòâåðaeäàþò èììóííóþ îñíîâó ÃÒÄ. Äëÿ âñå áîëüøåãî ÷èñëà ïðåïàðàòîâ (íàïðèìåð, ôëóêëîêñàöèëëèí [9], àóãìåíòèí (àìîêñèöèëëèí + êëàâóëàíîâàÿ êèñëîòà) [10], ëþìèðàêîêñèá [44], ëàïàòèíèá [4], êñèìåëàãàòðàí [40], èçîíèàçèä [16], òèêëîïèäèí [34], ìèíîöèêëèí [6], òåðáèíàôèí [5]) èññëåäîâàíèÿ ãåíîìíîé àññîöèàöèè âûÿâèëè ñïåöèôè-÷åñêèå àëëåëè HLA êàê âàaeíûå ôàêòîðû âîñïðèèì÷èâîñòè. Ýòè äàííûå ñâèäåòåëüñòâóþò î òîì, ÷òî ëåêàðñòâåííûé àíòèãåí âçàèìîäåéñòâóåò ñ ìîëåêóëîé HLA äëÿ àêòèâàöèè Ò-êëåòîê ó âîñïðèèì÷èâûõ ïàöèåíòîâ.…”

The problem of safety of lipid-lowering therapy

“…При выраженных нарушениях функции печени возвращение к терапии статинами является мало освещенной проблемой. Имеются малочисленные и противоречивые публикации о результатах возобновлении терапии статинами после выраженного повреждения печени, которые не позволяют выработать единого подхода [52,63].…”

“…Другие липидснижающие препараты (фибраты и в особенности фенофибрат) [51], эзетемиб также способны вызвать нарушение функции печени [64,65]. Совместное применение эзетемиба и статинов может усилить пагубное воздействие на печень [63].…”