Statins myotoxicity

A potential drug interaction between simvastatin and danazol, causing rhabdomyolysis and acute renal insufficiency, has been reported (43). Rhabdomyolysis can occur with all statins when they are used alone and particularly when they are combined with other drugs that are themselves myotoxic or that increase the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral systemic availability. 

It has been proposed that the risk of myotoxicity increases when statins are prescribed concurrently with erythromycin (83). There are no data for any pharmacokinetic interaction with fluvastatin or pravastatin, but as in the case of simvastatin the major route of metabolism of these drugs is by CYP3A4 and there is potential for an adverse interaction. 

Drugs that cause unintended muscle injury can also exhibit fiber-type specificity (Bakhtiar, 2008 Kuncl, 2009). Again the statins serve as an instructive example. Preclinical studies in rats have shown that statin-induced muscle injury predominately affects the fast glycolytic fibers (Smith et al., 1991 Westwood et al., 2005). Conversely, fibrates have been shown to exhibit a type 1 fiber specificity both for efficacy and myotoxicity (De Souza et al., 2006). The differences in protein expression, metabolism, and mitochondrial function and number between the fiber types have been implicated in the differences seen in the sensitivity to particular drugs (Sirvent et al., 2008 Kuncl, 2009 Anadon et al., 2014). Identifying a fiber-type specific effect is currently done by immunohistochemistry, which is labor intensive and limits the feasibility of assessing routinely in preclinical studies. Further, a muscle biopsy would be required in clinical studies, which is impractical in most situations. 

Sirvent, P, J. Mercier, and A. Lacampagne (2008). New insights into mechanisms of statin-associated myotoxicity. Curr Opin Pharmacol 8(3) 333-338. 

Weakness can result from medications that have a direct myotoxic effect, such as blockade of myocyte glycoprotein synthesis and eleetron transport eaused by statins (inhibitors of the hydroxy-methylglutaryl-coenzyme A reduetase) used in patients with hyperlipidemia or nucleoside analogues used in patients with human immunodefieieney virus (40). Weakness can also result from neuromuscular blocking agents and aminoglyeosides, which interfere with neuromuscular transmission. 

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