Ritonavir Atorvastatin

C4H7CIO 79-30-1) see Atorvastatin calcium Flutamide Ibopamine Mibefradil hydrochloride Ritonavir isochroman... 

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... 

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. 

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

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

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... 

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... 

Transporter efflux transporter effects predominant Examples Amiodarone Atorvastatin Azithromycin Carbamazepine Carvediioi Chlorpromazine Ciprofloxacin Cisapride Cyciosporine Danazoi Dapsone Diclofenac Diflunisal Digoxin Erythromycin Flurbiprofen Glipizide Glyburide Griseofulvin Ibuprofen Indinavir Indomethacin Itraconazole Ketoconazole Lansoprazole Lovastatin Mebendazole Naproxen Nelfinavir Ofloxacin Oxaprozin Phenazopyridine Phenytoin Piroxicam Raloxifene Ritonavir Saquinavir Saquinavir Sirolimus Sirolimus Spironolactone Spironolactone Tacrolimus Tacrolimus ... 

Mah Ming JB, Gill MJ. Drug-induced rhabdomyolysis after concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir in a tient with HIV AIDS Patient Care STDS (2003) 17,207-10. 

The levels of atorvastatin and simvastatin are markedly increased by lopinavir and saquinavir (with ritonavir), nelfinavir, and ritonavir alone. Pravastatin seems only moderately affected. Several cases of rhabdomyolysis have been attributed to this interaction. 

Either atorvastatin 20 mg daily or pravastatin 20 mg daily were given to 24 healthy subjects for 4 days during a 14-day course of lopinavir/ritonavir 400/100 mg twice daily. The maximum serum levels and AUC of atorvastatin were increased by between 4.7- and 5.9-fold and the maximum serum levels and AUC of pravastatin were only increased by about 30%. Atorvastatin and pravastatin had no effect on the pharmacokinetics of lopinavir or ritonavir. ... 

Ritonavir 300 mg twice daily and saquinavir 400 mg twice daily were given to healthy subjects for 3 days, after which the dose was increased to ritonavir 400 mg twice daily and saquinavir 400 mg twice daily for a further 11 days. On the last 4 days atorvastatin, pravastatin, or simvastatin (all 40 mg daily) were also given. The mean pravastatin AUC was approximately halved (13 subjects), the mean atorvastatin AUC was increased approximately fourfold (14 subjects) and the mean simvastatin acid AUC was increased approximately 32-fold (14 subjects). No cases of rhabdomyolysis were noted. ... 

The protease inhibitors, especially ritonavir, are known to be strong inhibitors of the cytochrome P450 isoenzyme CYP3A4. The levels of statins metabolised by this isoenzyme (notably simvastatin, and to some extent atorvastatin) are therefore increased. See Lipid regulating drugs , (p.l086) for information on the metabolism of the individual statins. 

Carr RA, Andre AK, Bertz RJ, Hsu A, Lam W, Chai M, Chen P, Williams L, Bernstein B, Sun E. Concomitant administration of ABT-378/ritonavir (ABT-378/r) results in a clinically important pharmacdcinetic (PK) interaction with atorvastatin (ATO) but not xavastatin (PRA). Intersci ConfAntimicrob Agents Chemother (2000) 40, 334. 

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