Ritonavir Atazanavir

Jacobson IM, Everson GT, Gordon SC, Kauffman R, McNair L, Muir A, McHutchison JG (2007) Interim analysis results from a phase 2 study of telaprevir with peginterferon alfa-2A and ribavirin in treatment-naive subjects with hepatitis C. AASLD 58th Annual Meet, Abstract 177 Johnson M (2006) Response to Atazanavir/ritonavir versus lopinavir/ritonavir equivalent or different efficacy profiles by HUl. AIDS 20 1987... 

Lopinavir/ritonavir or atazanavir/ritonavir and (zidovudine or fosamprenavir/ritonavir or tenofovir) and (lamivudine or emtricitabine). 

Other protease inhibitors-The coadministration of atazanavir/ritonavir and other protease inhibitors would be expected to increase exposure to the other protease inhibitor. Such coadministration is not recommended. 

Etravirine NNRTI 200 mg bid Take after a meal do not take on an empty stomach. Rash, nausea, diarrhea See footnote 4 for contraindicated medications. Do not administer with other NNRTIs, indinavir, atazanavir-ritonavir, fosamprenavir-ritonavir, tipranavir-ritonavir, or any unboosted PI... 

Atazanavir Ritonavir Fosamprenavir, didanosine, efavirenz, etravirine, stavudine, tenofovir... 

Preferred regimen Efivarenz Atazanavir + ritonavir Fosamprenavir + ritonavir Lopinavir/ ritonavir Tenofovir/ emtricitabine Zidovudine/ lamivudine... 

CLARITHROMYCIN, ERYTHROMYCIN PROTEASE INHIBITORS Possibly t adverse effects of macrolide with atazanavir, ritonavir (with or without lopinavir) and saquinavir Inhibition of CYP3A4- and possibly CYP1 A2-mediated metabolism. Altered transport via P-gp may be involved. Amprenavir and indinavir are also possibly t by erythromycin Consider alternatives unless there is Mycobacterium avium intracellulare infection if combined, 1 dose by 50% (75% in the presence of renal failure with a creatinine clearance of <30mL/min)... 

RIFABUTIN PROTEASE INHIBITORS t efficacy and t adverse effects of rifabutin Inhibition of CYP3A4-mediated metabolism. Nelfinavir also competitively inhibits 2C19 1 rifabutin dose by at least 50% when given with amprenavir, indinavir or nelfinavir, and by 75% with atazanavir, ritonavir (with or without lopinavir) or tipranavir... 

Atazanavir, atazanavir/ritonavir, lopinavir/ritonavir and saquinavir markedly increased the AUC of maraviroc by about three to fivefold in healthy subjects. Ritonavir-boosted saquinavir had an even greater effect (alraut tenfold). In contrast, tiprana-vir/ritonavir had no effect. Ketoconazole caused a fivefold increase. The manufacturer su ests that the dose of maraviroc should be halved when used with protease inhibitors. 

Atazanavir 400 mg daily inereased the AUC and maximum level of maraviroe by 257% and 109%, respeetively. Atazanavir/ritonavir 300/100 mg inereased the AUC of maraviroe by almost fivefold. In a study in HIV-positive patients, the AUC of a single 300-mg oral dose of... 

Atazanavir/Ritonavir 400/100 mg once dailyl (UK) 300/100 mg once daily (US) In the absence of data, avoid... 

Proton pump inhibitors. The AUC of atazanavir was reduced by 76% and the trough plasma level by 78% when atazanavir/ritonavir 300/100 mg was given with omeprazole 40 mg. Increasing the dose of atazanavir/ritonavir to 400/100 mg did not negate the effects of this interaction. An even greater effect (94% reduction in AUC) was seen when atazanavir alone was given with omeprazole, and the same effect was seen with lansoprazole. Similar results were found in another study with omeprazole ritonavir levels were not affected. ... 

Atazanavir trough levels were significantly lower in patients taking proton pump inhibitors than in those taking H2-receptor antagonists in another studyA 65-year-old HIV-positive man had a marked reduction in atazanavir trough levels and AUC in a 12-hour study while receiving esomeprazole and atazanavir/ritonavir. ... 

Quinidine sulphate 200 mg was given to 10 healthy subjects, followed 1 hour later by a single 400-mg dose of indinavir. Quinidine had no clinically significant effects on the pharmacokinetics of indinavir. However, indinavir is predicted to increase quinidine levels, and the US manufacturer recommends caution and monitoring of quinidine ieveis. Lopinavir/ritonavir is also predicted to increase quinidine levels, and the combination should be monitored. Similarly, atazanavir/ritonavir, darunavir/ritonavir, amprenavir and fosamprenavir ate predieted to increase quinidine levels, and the UK manufacturers contraindieate the combinations "" while the US manufacturers recommend monitoring quinidine concentrations. Conversely, for saquinavir/ritonavir, the UK manufacturer recommends caution and monitoring quinidine levels, and the US manufacturer eontraindicates the combination. Both the UK and US manufacturers contraindicate the use of quinidine with nelfinavir, ritonavir or tipranavir/ritonavir. ... 

The manufacturer notes that combining atazanavir 300 mg once daily with darunavir/ritonavir 400/100 mg twice daily did not significantly alter the AUC and minimum level of darunavir. In addition, the AUC and minimum level of atazanavir were not significantly changed, when compared with atazanavir/ritonavir 300/100 mg once daily alone, although the minimum level was increased by 52%. ... 

Rifampicin (rifampin) bioavaiiabiiity is increased by indinavir, but amprenavir has no effect. Rifampicin markedly reduces the bioavailability of amprenavir, atazanavir/ritonavir, indinavir, indinavir with ritonavir, iopinavir/ritonavir, nelfinavir and saquinavir, but oniy modestiy reduces that of ritonavir. The effects of rifampicin on iopinavir/ritonavir and saquinavir/ritona-vir can be overcome by increasing the protease inhibitor dose, but this appears to increase adverse effects (hepatotoxicity). 

Atazanavir/ritonavir Rifabutin dose reduced by up to 75% (150 mg every other day or three times per week). Atazanavir/ritonavir dose unchanged. Not recommended (atazanavir levels markedly reduced). 3, 12, 13... 

Atazanavir/ritonavir, darunavir/ritonavir and lopinavir/ritonavir modestly increased the levels of tenofovir, and there is at least one case report of nephrotoxicity with the combination of tenofovir, didanosine, and lopinavir/ritonavir. Saquinavir/ritonavir, ti-pranavir/ritonavir, and probably also fosamprenavir/ritonavir, have little effect on tenofovir levels. Tenofovir modestly decreased atazanavir levels, and this was minimised when ritonavir was also given. Tenofovir had no important effect on ritonavir-boosted darunavir, lopinavir, and tipranavir levels, and modestly increased those of ritonavir-boosted saquinavir in one of two studies. Indinavir and nelfinavir do not interact pharmacokineti-cally with tenofovir. 

When atazanavir 300 mg once daily was given with ritonavir 100 mg once daily (as a pharmacokinetic booster), tenofovir disoproxil fumarate 300 mg once daily reduced the AUC of atazanavir by a similar amount (25%), but had less effect on the trough level (23% reduction), when compared with atazanavir/ritonavir alone. Similarly, the pharmacokinetics of atazanavir/ritonavir did not differ significantly between patients taking tenofovir and those not. Combined use increased the tenofovir AUC by 37% and the minimum level by 29%. - ... 

The interaction of methadone (20-175 mg/ day) and atazanavir/ritonavir (300/100 mg/ day) has been investigated in 24 HIV-1-positive patients, who were randomized to methadone or just the antiretroviral drugs [125. The dose of methadone correlated significantly with the maximum plasma concentration of atazanavir, resulting in a reduced plasma concentration. 

Van Luin M, Van der Ende ME, Richter C, Visser M, Faraj D, Van der Ven A, Gelinck L, Kroon F, Wit FW, Van Schaik RHN, Kuks PFM, Burger DM. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritona-vir or atazanavir/ritonavir. AIDS 2010 24... 

Nevirapine Co-administration of atazanavir- -ritonavir 300/100 mg/day plus nevirapine 200 mg bd resulted in a reduction in atazanavir by nearly half [110 ]. Monitoring of atazanavir concentrations is recommended in patients taking this drug combination, and it might be necessary to increase the dose of atazanavir. 

HIV-infected adults receiving atazanavir and atazanavir/ritonavir systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2010 65(9) 1878-88. 

Molto J, Deig E, Valle M, Maria Llibre J, Miranda C, Cedeno S, Valero S, Negredo E, Clotet B. Effect of nevirapine on the steady-state trough concentrations of atazanavir in HTV-infected patients receiving atazanavir/ritonavir. Ther Drug Monit 2010 32(1) 93-6. 

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