Cyclosporine with statins

Launay-Vacher V, Izzedine H, Deray G (2005) Statins dosage in patients with renal failure and cyclosporine drug-drug interactions in transplant recipient patients. Int J Cardiol 101 9-17. 

Clinically important, potentially hazardous interactions with cyclosporine, HMG CoA reductase inhibitors (statins), MAO inhibitors... 

Clinically important, potentially hazardous interactions with atorvastatin, bexarotene, cyclosporine, dicumarol, ezetimibe, fluvastatin, interferon alfa, lovastatin, nicotinic acid, pioglitazone, pravastatin, repaglinide, rosuvastatin, roxithromycin, simvastatin, statins, warfarin... 

OATPIBI, 1B3, and OATP2B1, in particular, are highly expressed in the human liver and are involved in the active hepatic uptake of various drugs. This active hepatic drug uptake process can be subject to inhibition resulting in higher blood levels and in a range of severe side effects such as those reported for statins after coadministration with the OATP inhibitor cyclosporin [22]. 

Drug interactions mediated by CYP3A inhibition can be severe e.g., nephrotoxicity induced by cyclosporine and tacrolimus and rhabdomyolysis resulting from increased levels of statins). Whenever an inhibitor of the CYP3A isoforms is administered, the clinician must be cognizant of the potential for serious interactions with drugs metabolized by CYP3A. 

Cyclosporine increases the systemic exposure of all statins (lovastatin, simvastatin, pravastatin, cerivastatin, and rosuvastatin), due to drug-drug interaction (via either CYPs or transporters like P-gp and OATP) in the liver. Rosuvastatin has been shown to be a substrate for the human liver transporter OATP2 and BCRP, but not P-gp. It s metabolic clearance is low and mainly mediated by CYP2C9. CsA treatment in transplant recipients increased AUCq 2h and Cmax of rosuvastatin (10 mg) by 7.1 and 10.6-fold, respectively, compared with control values, due to CsA inhibition of OATP2-mediated rosuvastatin hepatic uptake (Simonson et al., 2004). 

Some inducers of CYP3A4 are also inducers of P-glycoprofein These include dexamethasone, rifampin and St. John s wort. The last two have been implicated in the induction of the metabolism of cyclosporin, certain HMG-CoA reductase inhibitors (statins) and several HIV protease inhibitors, with resulting loss of efficacy of these compounds. 

---