Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy

Pogson, G W; Kindred, Lynn H.; Carper, Bradford G

doi:10.1016/s0002-9149(99)00034-x

Cited by 94 publications

(42 citation statements)

References 12 publications

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“…This is of particular importance with agents that are also metabolized by cytochrome P450 3A4 such as gemfibrozil. 33,37,55,[60][61][62][63][64][65][66] Thus, the statins are functionally equivalent and the choice of drug is largely determined by individual patient needs and tolerability.…”

Section: The Statin Family Of Drugsmentioning

confidence: 99%

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

et al. 2002

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The statin family of drugs target HMG-CoA reductase, the ratelimiting enzyme of the mevalonate pathway, and have been used successfully in the treatment of hypercholesterolemia for the past 15 years. Experimental evidence suggests this key biochemical pathway holds an important role in the carcinogenic process. Moreover, statin administration in vivo can provide an oncoprotective effect. Indeed, in vitro studies have shown the statins can trigger cells of certain tumor types, such as acute myelogenous leukemia, to undergo apoptosis in a sensitive and specific manner. Mechanistic studies show bcl-2 expression is down-regulated in transformed cells undergoing apoptosis in response to statin exposure. In addition, the apoptotic response is in part due to the depletion of the downstream product geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate or other products of the mevalonate pathway including cholesterol. Clinically, preliminary phase I clinical trials have shown the achievable plasma concentration corresponds to the dose range that can trigger apoptosis of tumor types in vitro. Moreover, little toxicity was evident in vivo even at high concentrations. Clearly, additional clinical trials are warranted to further assess the safety and efficacy of statins as novel and immediately available anti-cancer agents. In this article, the experimental evidence supporting a role for the statin family of drugs to this new application will be reviewed.

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Section: The Statin Family Of Drugsmentioning

confidence: 99%

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

et al. 2002

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“…Fatal rhabdomyolysis after cerivastatin treatment was reported most frequently when the drug was combined with the lipid lowering fibrate gemfibrozil (Pogson et al, 1999;Farmer, 2001;Staffa et al, 2002). Gemfibrozil increases the risk of myopathy associated with simvastatin and lovastatin, too.…”

mentioning

confidence: 99%

Gemfibrozil Inhibits CYP2C8-Mediated Cerivastatin Metabolism in Human Liver Microsomes

Wang¹,

Neuvonen²,

Xia³

et al. 2002

Drug Metab Dispos

167

159

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“…Cases of rhabdomyolysis associated with cerivastatin used in combination with other drugs, such as gemfibrozil and cyclosporins [1][2][3], have been reported, and in some cases rhabdomyolysis has led to acute renal failure (ARF) [4]. Here we report the case of a patient treated with cerivastatin only, who developed rhabdomyolysis and ARF.…”

mentioning

confidence: 92%

Cerivastatin Induces Rhabdomyolysis and Acute Renal Failure

Paolo

Monaci

Cappelletti

et al. 2002

Nephron

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Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy

Cited by 94 publications

References 12 publications

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

Gemfibrozil Inhibits CYP2C8-Mediated Cerivastatin Metabolism in Human Liver Microsomes

Cerivastatin Induces Rhabdomyolysis and Acute Renal Failure

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