Simvastatin Bosentan

Concomitant treatment with simvastatin and bosentan (the first orally active endothelin receptor antagonist) reduces exposure to simvastatin by about 40%, suggesting that in vivo bosentan is a mild inducer of CYP3A4 (38). 

Dingemanse J. Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Chn Pharmacokinet 2003 42 293-301. 

Isoniazid Avasimibe Bosentan Carbam- a2epine" Clotrimazole Cyproterone acetate Hyperforin Lovastatin Mifepristone Nelfinavir Nifedipine Omeprazole Paclitaxel Phenobarbital Phenytoin Rifabutin Rifampin"" Rifapentine Ritonavir Simvastatin Sulfinpyrazole Topotecan Troglitazone Troleandomycin Vitamin E Vitamin K2 Yin zhi wuang... 

VASODILATOR ANTIHYPERTENSIVES LIPID-LOWERING DRUGS Bosentan lowers simvastatin levels Uncertain bosentan moderately inhibits CYP3A4 Monitor lipid profile closely look for poor response to simvastatin... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

Bosentan modestly reduces the AUC of simvastatin and its active metabolite, which could lead to a reduction in simvastatin efficacy. 

In a three-way, erossover study, 9 healthy subjects were given either bosentan 125 mg twiee daily for 5.5 days, simvastatin 40 mg daily for 6 days, or both treatments together. Simvastatin had no effect on the phar-macokineties of bosentan, but bosentan reduced the AUC of simvastatin and its p-hydroxyacid metabolite by 34% and 46%, respectively. ... 

Bosentan is known to be a mild indueer of the cytochrome P450 isoenzyme CYP3A4, which is involved in the metabolism of simvastatin. In-duetion of simvastatin metabolism may have led to the redueed levels seen. See Lipid regulating drugs , (p.l086) for more information on the metabolism of all the statins. 

A 40% reduction in the AUC of simvastatin is potentially clinically significant. If bosentan and simvastatin are used eoncurrently it would seem prudent to monitor the outcome to ensure that simvastatin is effective. 

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