Simvastatin Ritonavir

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Chemotherapy Cyclophosphamide, erlotlnlb, ifos-famide, paclitaxel, tamoxifen, vinblastine, vincristine HIV protease inhibitors Amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir HMG-CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin... 

St. John s wort Alprazolam, cyclosporine, digoxin, indinavir, oral contraceptives, ritonavir, simvastatin, tacrolimus, warfarin... 

Itraconazole Alfentanil, alprazolam, astemizole, atorvastatin, buspirone, cisapride, cyclosporine, delavirdine, diazepam, digoxin, felodipine, indinavir, loratadine, lovastatin, midazolam, nisoldipine, phenytoin, quinidine, ritonavir, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, triazolam, verapamil, warfarin... 

Tipranavir both inhibits and induces the CYP3A4 system. When used in combination with ritonavir, its net effect is inhibition. Tipranavir also induces P-glycoprotein transporter and thus may alter the disposition of many other drugs (Table 49-4). Concurrent administration of tipranavir with fosamprenavir or saquinavir should be avoided owing to decreased blood levels of the latter drugs. Tipranavir/ritonavir may also decrease serum levels of valproic acid and omeprazole. Levels of lovastatin, simvastatin, atorvastatin, and rosuvastatin may be increased, increasing the risk for rhabdomyolysis and myopathy. 

Healthy volunteers were given protease inhibitors and statins, and the authors concluded that simvastatin should be avoided and that atorvastatin could be used with caution in people taking ritonavir and saquinavir (111). Dosage adjustment of pravastatin may be necessary with co-administration of ritonavir and saquinavir. Pravastatin does not alter the pharmacokinetics of nelfinavir, and thus appears to be safe for co-administration. 

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... 

A4/3A5 Midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, triazolam Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Rifampin, carbamazepine... 

CYP3A4 Inhibition Amiodarone, clarithromycin, erythromycin, cimetidine, cyclosporine, fluoxetine fluvoxamine, itraconazole, ketoconazole, nefazodone, verapamil, diltiazem HIV antivirals delaviridine, indanavire, nelfmavire, ritonavire, sequinavire Atorvastatin Lovastatin Simvastatin ... 

An interaction of ritonavir with simvastatin reportedly resulted in rhabdomyolysis (32). 

A 51-year-old woman taking zidovudine, lamivudine, indinavir, and simvastatin started to take ritonavir and after 1 week developed diffuse muscle weakness and body aches. Creatine kinase (total and the MB isozyme), lactate dehydrogenase, and transaminases were all raised. There were crystals and hemoglobin in the urine. 

Cheng CH, Miller C, Lowe C, Pearson VE. Rhabdomyolysis due to probable interaction between simvastatin and ritonavir. Am J Health Syst Pharm 2002 59(8) 728-30. 

There has been a study of the effects of ritonavir 400 mg bd plus saquinavir soft-gel capsules 400 mg bd on the pharmacokinetics of pravastatin, simvastatin, and atorvas-tatin (40 mg/day each), and of the effect of pravastatin on the pharmacokinetics of nelfinavir in a randomized, open study in 56 healthy HIV-negative adults (46). Ritonavir - -saquinavir reduced the steady-state AUC of pravastatin, markedly increased the AUC of simvastatin, and slightly increased the AUC of total active atorvastatin. The AUCs of nelfinavir and its active M8 metabolite were not altered by pravastatin. The authors concluded that simvastatin (and by implication lovastatin, which in... 

GR is a 55-year-old HIV positive man currently receiving ritonavir/lopinavir, nevirapine, and lamivudine. You would like to start simvastatin to decrease his triglycerides. Which of his ARVs will interact with simvastatin ... 

E Simvastatin is metabolized by CYP3A4. Nevirapine is an inducer of CYP3A4, whereas lopinavir and ritonavir are inhibitors of CYP3A4. Thus, the effect of these two drugs on simvastatin levels is unpredictable. Lamivudine is not metabolized by the CYP450 system and will not affect simvastatin levels. 

Clinically important, potentially hazardous interactions with abarelix, acenocoumarol, amisulpride, amprenavir, anisindione, anticoagulants, arsenic, astemizole, carbimazole, celiprolol, ciprofloxacin, dabigatran, degarelix, dicumarol, digoxin, diltiazem, enoxacin, fentanyl, fosamprenavir, gatifloxacin, grapefruit juice, lomefloxacin, methotrexate, moxifloxacin, nilotinib, norfloxacin, ofloxacin, oxprenolol, quinidine, quinolones, rifabutin, rifampin, rifapentine, ritonavir, simvastatin, sparfloxacin, sulpiride, tacrolimus, tipranavir, verapamil, warfarin, zuclopenthixol... 

Clinically important, potentially hazardous interactions with bepridil, cisapride, dasatinib, dofetilide, ergot derivatives, etravirine, fentanyl, fesoterodine, garlic, indinavir, irinotecan, ixabepilone, lapatinib, lovastatin, marihuana, midazolam, pimozide, proton-pump inhibitors, raltegravir, rifampin, ritonavir, sildenafil, simvastatin, solifenacin, St John s wort, temsirolimus, triazolam... 

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 cyclosporine, diltiazem, dofetilide, erythromycin, grapefruit, ketoconazole, quinidine, ritonavir, simvastatin, sotalol, thioridazine, verapamil, ziprasidone... 

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