Simvastatin 4- Saquinavir

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... 

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... 

Interactions with drugs have also been demonstrated for flavonoids from citrus. Naringin and naringenin were shown to interact with simvastatin and saquinavir in in vitro experiments (41,42) and caused alterations in the pharmacokinetics of quinine in rats (44). Moreover, naringenin and naringin were found to inhibit the OATP-B-mediated uptake of estrone-3-sulfate into human embryonic kidney cells (23). 

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. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

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. 

Grapefruit juice has also been shown to inhibit CYP3A4 and P-gp in the small intestine, and hence, can elevate the oral bioavailability of lipophilic drugs [98,99]. Concomitant intake of grapefruit juice with the lipophilic cholesterol-lowering medication simvastatin caused a 16-fold increase in the AUC of simvastatin [100]. The oral bioavailability of the lipophilic HIV protease inhibitor saquinavir was doubled following concomitant administration with grapefruit juice [101]. 

This approach can be easily reproduced with other CYP3A-sensitive substrates, such as buspirone, triazolam, and eplerenone, and yields quantitative examination of the relationship between these sensitive substrates and midazolam. This question was pursued in some depth by Ragueneau-Majlessi et al. (22) and showed that classification of inhibitors (five moderate and eight potent) was substrate independent in 74% to 83% of the instances. Exceptions pertained to buspirone and simvastatin that seemed to be systematically more sensitive than midazolam and saquinavir that appeared less sensitive (22). Furthermore, results of this analysis allow an extrapolation of the inhibitory effect of a compound from one probe to another avoiding a duplication of studies (i.e., effects of inhibitor on simvastatin calculated from its effect on midazolam). 

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

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 astemizole, carbamazepine, cisapride, dihydroergotamine, ergotamine, lovastatin, midazolam, phenobarbital, phenytoin, pimozide, pravastatin, rifampin, saquinavir, simvastatin, St John s wort, terfenadine, triazolam... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Methylprednisolone Midazolam Nisoldipine Phenytoin Pimozide Quinidine Ritonavir Saquinavir Sildenafil Simvastatin SiroUmus Sulfonylureas (glyburide, others) Tacrolimus Triazolam Trimetrexate Verapamil Ritonavir... 

---