Pravastatin Cyclosporine

Concomitant immunosuppressants- In patients taking immunosuppressive drugs such as cyclosporine concomitantly with pravastatin, begin therapy with pravastatin 10 mg once/day at bedtime and titrate to higher doses with caution. Most patients treated with this combination received a maximum pravastatin dose of 20 mg/day. 

Drugs that may interact with orlistat include cyclosporine, fat-soluble vitamins, pravastatin, and warfarin. 

The catabolism of lovastatin, simvastatin, and atorvastatin proceeds chiefly through CYP3A4, whereas that of fluvastatin and rosuvastatin is mediated by CYP2C9. Pravastatin is catabolized through other pathways, including sulfation. The 3A4-dependent reductase inhibitors tend to accumulate in plasma in the presence of drugs that inhibit or compete for the 3A4 cytochrome. These include the macrolide antibiotics, cyclosporine, ketoconazole and its congeners, HIVprotease inhibitors, tacrolimus, nefazodone, fibrates, and others (see Chapter 4). Concomitant use of reductase inhibitors with amiodarone or verapamil also causes an increased risk of myopathy. 

Regazzi MB, Iacona I, Campana C, et al. Altered disposition of pravastatin following concomitant dmg therapy with cyclosporine A in transplant recipients. Transplant Proc 1993 25 2732-2734. 

Inhibitors of OATP transport are typically ster-ically bulky compounds, including anions, cations, and neutral compounds (95). Various medications have been shown to interact with OATPs, including HMG CoA reductase inhibitors, cyclosporine, quinidine, rifampin, ketoconazole, verapamil, and certain protease inhibitors. Cyclosporine and rifampin have relatively high ratios of plasma concentration to Ki, suggesting the potential for clinically significant drug-drug interactions via modulation of OATP. On the other hand, plasma concentrations of pravastatin are... 

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

Olbricht C, Wanner C, Eisenhauer T, Khem V, Doll R, Boddaert M, O Grady P, Krekler M, Mangold B, Christians U. Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses. Chn Pharmacol Ther 1997 62(3) 311-21. 

Li C, Yang CW, Park JFI, Lim SW, Sun BK, Jung JY, Kim SB, Kim YS, Kim J, Bang BK. Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy. Am J Physiol Renal Physiol 2004 286 F46-57. 

Li C, Lim SW, Choi BS, Lee SFI, Cha JFI, Kim IS, Kim J, Yang CW. Inhibitory effect of pravastatin on transforming growth factor betal-inducible gene h3 expression in a rat model of chronic cyclosporine nephropathy. Am J Nephrol 2005 25 611-620. 

Clinically important, potentially hazardous interactions with astemizole, atorvastatin, cyclosporine, fluvastatin, lovastatin, pimozide, pravastatin, rifabutin, simvastatin, warfarin... 

Clinically important, potentially hazardous interactions with alprazolam, aprepitant, astemizole, atorvastatin, benzodiazepines, carbamazepine, chlordiazepoxide, cilostazol, clonazepam, clorazepate, colchicine, conivaptan, cyclosporine, dabigatran, dasatinib, diazepam, digoxin, dihydroergotamine, disopyramide, ergot alkaloids, fesoterodine, fluoxetine, flurazepam, fluvastatin, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lorazepam, lovastatin, methylprednisolone, methysergide, midazolam, nilotinib, oxazepam, paroxetine, pimozide, pravastatin, prednisone, quazepam, repaglinide, rimonabant, rivaroxaban, sertraline, silodosin, simvastatin, solifenacin, temazepam, temsirolimus, tolvaptan, trabectedin, triazolam, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

Figure 11.9 Different effects of itraconazole and obtained from the previous literature. The details cyclosporin A on the plasma AUC of pravastatin, are described in the Section 11.7.1. BA simvastatin, and atorvastatin [210, 221-224], bioavailability, Fa Fg fraction of dose absorbed The fold-increase in the plasma AUC of statins from the small intestine to the portal vein, Fh was expressed after coadministration of hepatic availability,...

Regazzi, M.B., Iacona, I., Campana, C., Raddato, V., Lesi, C., Perani, G., Gavazzi, A. and Vigano, M. (1993) Altered disposition of pravastatin following concomitant drug therapy with cyclosporin A in transplant recipients. 

MRP2 GSH conjugates, glucuronides, sulfate conjugates, methotrexate, temocaprilat, CPT11 carboxylate, SN38 carboxylate, cisplatin, pravastatin MK571, cyclosporin A... 

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). 

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