Fluvastatin drug interactions

Fischer, V., Johanson, L., Heitz, F., Tullmann, R., Graham, E., Baldeck, J.P. and Robinson, W.T., The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab. Dispos., 1999, 27, 410 16. 

Most drug interactions associated with rhabdomyolysis occur when ciclosporin is combined with simvastatin or lovastatin. It has been suggested that if a statin is to be combined with ciclosporin, pravastatin or fluvastatin should be chosen instead (80). 

Andrus MR. Oral anticoagulant drug interactions with statins case report of fluvastatin and review of the literature. Pharmacotherapy 2004 24(2) 285-90. 

Noe, J., Portmann, R., Brun, M., and Funk, C. (2007) Substrate dependent drug-drug interactions between gemfibrozil, fluvastatin and other OATP substrates on OATPIBI, OATP2B1 and OATP1B3. Drug Metabolism and Disposition, 35, 1308-1314. 

All other statins, which entered the market, are produced by total synthesis (Fig. 5.153). Fluvastatin is marketed as the racemate. After the Lipobay scandal, cerivastatin was withdrawn from the market worldwide in 2001, due to reports of fatal rhabdomyolysis associated with renal failure. The reasons behind these toxicities were a too narrow therapeutic window (effective dose compared to toxic dose) and the drug interaction with fibrates, especially with gemfibrozil. 

Physicians should check for lipid-lowering drugs before treating elderly individuals with itraconazole (73). Susceptibility to this interaction varies from statin to statin, in that simvastatin is more affected than pravastatin (74). Concomitant use of simvastatin with itraconazole should be avoided, and the same holds true for atorvastatin (75). In another study, the blood concentration of fluvastatin was not significantly increased, whereas that of lovastatin was (76). 

The rate of myopathy with a statin alone in the general population is 0.1-0.5% and 0.2-2.5% with combination therapy. Rhabdomyolysis is very rare at 0.02-0.04%. However, the latter carries a significant morbidity and mortality. In a review of Food and Drug Administration (FDA) reports published in 2002, there were 38 deaths in 631 patients (6.3%) [31]. Pravastatin and fluvastatin have been less frequently implicated in fatal cases of rhabdomyolysis [31]. It is postulated that the more hepatoselective hydrophilic statins, such as pravastatin, are less likely to penetrate muscle cells than are lipophilic statins, and therefore represent a lower risk for myopathy, particularly in the event of an interacting drug increasing their blood levels to within the toxic range [26, 32]. 

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. 

In a randomised, erossover study 32 otherwise healthy subjects with hy-pereholesterolaemia were given either ezetimibe 10 mg daily, fluvastatin 20 mg daily or both drugs in combination for 14 days. The combination was well tolerated, no significant pharmacokinetic interaction occurred, and an enhanced lowering of LDL-cholesterol was noted, which was considered to be clinically favourable. However, a case report describes a 52-year-old man taking fluvastatin 80 mg daily who developed elevated creatinine kinase levels 8 weeks after ezetimibe 10 mg daily was added. 

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