Ritonavir Darunavir

Qotet B, Bellos N, Mohna JM, Cooper D, et al. 2007. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2 A pooled subgroup analysis of data from two randomized trials. Lancet. 369 1169-1178. 

Darunavir/Ritonavir 300/100 mg twice daily 21% increase 31 % decrease in Cmin (darunavir) 12... 

Darunavir/Ritonavir Care No dose adjustments required... 

Pharmacokinetic changes have been seen with the concurrent use of ketoconazole and darunavir/ritonavir the darunavir AUC was raised by 42% and the ketoconazole AUC was increased about threefold. ... 

Proton pump inhibitors (marked effect) and H2-receptor antagonists (modest effect) reduce atazanavir levels. Other drugs that increase gastric pH are also predicted to reduce plasma levels of atazanavir. Fosamprenavir may be similarly affected (moderate effects seen with ranitidine), although antacids and esomeprazole had little effect in one study. Omeprazole decreases indinavir levels and an antacid modestly decreased tipranavir levels. Neither ranitidine nor omeprazole had any effect on darunavir/ritonavir or lopinavir/ritonavir levels. In contrast, cimetidine, ranitidine and omeprazole have been shown to increase saquinavir levels. 

In a crossover study in 16 healthy subjects, neither omeprazole 20 mg daily nor ranitidine 150 mg twice daily had a significant effect on the AUC or minimum level of darunavir after darunavir/ritonavir 400/100 mg was given twice daily for 5 days. ... 

Omeprazole and ranitidine do not appear to alter the pharmacokinetics of darunavir/ritonavir or lopinavir/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%. ... 

The manufaeturer notes that eombining lopinavir/ritonavir 400/100 mg with darunavir/ritonavir 300/100 mg, both twice daily, increased the AUC and minimum level of lopinavir by 37% and 72%, respectively, whereas the AUC and minimum level of damnavir were decreased by 53% and 65%, respectively. 

Although there are no data, the manufacturer predicts that rifabutin will decrease ritonavir-boosted darunavir levels, and that darunavir/ritonavir will increase rifabutin levels. They also predict that rifampicin will markedly reduce ritonavir-boosted darunavir levels. ... 

Darunavir/ritonavir Rifabutin dose reduced to 150 mg every other day. Not recommended (darunavir levels predicted to be markedly reduced). 14, 15... 

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. 

The manufacturer notes that concurrent use of darunavir/ritonavir 300/100 mg twice daily with tenofovir disoproxil fumarate 300 mg once daily modestly increased the tenofovir AUC and minimum level by 22% and 37%, respectively. Darunavir levels were not significantly changed (minimum level increased by 24%). ... 

Darunavir+ritonavir Darunavir+ritonavir had no effects on the pharmacokinetics of etravirine 400 mg/day in a multicenter, open, phase Ha trial in 21 treatment-naive patients aged 18 years and over with HTV-1 infections [93 ]. 

Dejesus E, Lalezari JP, Osiyemi OO, Ruane PJ, Ryan R, Kakuda TN, Witek J. Pharmacokinetics of once-daily etravirine without and with once-daily darunavir/ ritonavir in antiretroviral-naive HIV type-1-infected adults. Antivir Ther 2010 15(5) 711-20. 

Blanche S, Bologna R, Cahn P, Rugina S, Flyim P, Fortuny C, Vis P, Sekar V, Van Baelen B, Dierynck I, Spinosa-Guzman S. Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents. AIDS 2009 23(15) 2005-13. 

Sekar V, Lavreys L, Van de Casteele T, Berckmans C, Spinosa-Guzman S, Vangeneugden T, De Pauw M, Hoetelmans R. Pharmacokinetics of darunavir/ritonavir and rifabutin... 

Moltd J, Valle M, Miranda C, Cedeno S, Negredo E, Barbanoj MJ, Qotet B. Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother 2011 55(1) 326-30. 

Darunavir The interaction of ketoconazole with darunavir alone and in combination with low-dose ritonavir has been investigated in HIV-negative volunteers, who took ketoconazole 200 mg bd, darunavir 400 mg bd, darunavir 400 mg bd plus ketoconazole 200 mg bd, darunavir + ritonavir 400/ 100 mg bd, or darunavir + ritonavir 400/ 100 mg bd plus ketoconazole 200 mg bd all the treatments were taken with food for 6 days [3P]. Ketoconazole increased the AUCo uh Cmax tmd C in of darunavir by 155% (80, 261), 78% (28, 147), and 179% (58, 393) respectively. Darunavir AUCo uh... 

Cmcm Cmin increased by 42% (23, 65), 21% (4, 40), and 73% (39, 114) respectively during darunavir + ritonavir and keto-conazole co-administration. Ketoconazole pharmacokinetics were unchanged by coadministration of darunavir alone. Ketoconazole AUCq—,22h> max, and Cnun increased by 212% (165, 268), 111% (81,144), and 868% (544,1355) respectively during co-administration of darunavir + ritonavir. The increase in darunavir exposure by ketoconazole was lower than that observed previously with ritonavir. A maximum ketoconazole dose of 200 mg/day is recommended if it is used concomitantly with darunavir + ritonavir, and no dose adjustments of darunavir + ritonavir is required. 

Sekar VJ, Lefebvre E, De Pauw M, Vangeneugden T, Hoetelmans RM. Pharmacokinetics of darunavir/ritonavir and ketoconazole following co-administration in HIV-healthy volunteers. Br J Clin Pharmacol 2008 66 215-21. 

Darunavir ritonavir The interaction of etravirine 100 or 200 mg bd with darunavir -I- low-dose ritonavir 600/100 mg bd has been evaluated in an open, randomized, two-way crossover phase I study in 23 HIV-negative volunteers [160. Darunavir -I- ritonavir reduced the AUCo—izh of etravirine 100 mg bd by 37%, the C ax by 32%,... 

Comparative studies In an open randomized comparison of darunavir - - ritonavir and lopinavir - - ritonavir in 689 patients the former was associated with fewer possibly treatment-related grade 2-4 gastrointestinal adverse events (7 versus 14%) and specifically treatment-related moderate-to-severe diarrhea (4 versus 10%) adverse events that led to withdrawal occurred in 3% and 7% respectively [173. ... 

Oral contraceptives Norethindrone and ethinylestradiol concentrations were considerably reduced by the combination of darunavir + ritonavir in healthy volunteers [180 ]. 

Saquinavir The combination of saquinavir with darunavir + ritonavir is not recommended, as plasma concentrations of darunavir are increased [181 ]. 

Schbller-Gyiire M, Kakuda TN, Sekar V, Woodfall B, De Smedt G, Lefebvre E, Peelers M, Hoetehnans RM. Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HTV-negative volunteers. Antivir Ther 2007 12(5) 789-96. 

Ortiz R, Dejesus E, Khanlou H, Voronin E, van Lunzen J, Andrade-Villanueva J, Fourie J, De Meyer S, De Pauw M, Lefebvre E, Vangeneugden T, Spinosa-Guzman S. Efficacy and safety of once-daily darunavir/ritonavir versus lopi-navir/ritonavir in treatment-naive HIV-1-... 

Aouri M, Decosterd LA, Buclin T, Hirschel B, Calmy A, livio F. Drug interactions between voriconazole, darunavir/ritonavir and etravirine in an HIV-infected patient with Aspergillus pneumonia. AIDS 2012 26(6) 776-8. 

Nishijima T, Komatsu H, Teruya K, Tanuma J, Tsukada K, Gatanaga H, et al. Once-daily darunavir/ritonavir and abacavir/lamivudine versus tenofovir/emtridtabine for treatment-naive patients with a baseline viral load of more than 100000copies/mL. AIDS 2013 27(5) 839-42. 

Lorber M. A case of possible darunavir/ritonavir-induced peripheral neuropathy case description and review of the literature. J Int Assoc Provid AIDS Care 2013 12(3) 162-5. 

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