Tipranavir Lopinavir

Zidovudine Didanosine Stavudine Lamivudine Abacavir Tenofovir Emtricitabine Nevirapine Efavirenz TMC125 Saquinavir Indinavir Lopinavir Fosamprenavir Atazanavir Tipranavir Darunavir Raltegravir Elvitegravir Enluvirtide Maraviroc Vicriviroc Bevirimat... 

Women of reproductive potential prescribed efavirenz should be counseled on its potentially teratogenic effects and the importance of birth control. Additionally, nevirapine, nelfinavir, ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir have been shown to decrease the concentrations of estrogens and/or progestins in oral contraceptives, which could lead to failure.2 For patients prescribed these drugs, barrier forms of contraception are preferred to prevent pregnancy. DepoProvera may be... 

TC, lamivudine ABC, abacavir APV, amprenavir AST, aspartate aminotransferase ALT, alanine aminotransferase ATV, atazanavir CBC, complete blood cell count D/C, discontinue ddl, didano-sine d4T, stavudine EFV, efavirenz FTC, emtricitabine P1BV, hepatitis B virus F1CV, hepatitis C vims HIV, human immunodeficiency virus IDV, indinavir IV, intravenous LFT, liver function tests LPV/r, lopinavir + ritonavir NNRTI, nonnucleoside reverse transcriptase inhibitor NRTI, nucleoside reverse transcriptase inhibitor NVP, nevirapine PI, protease inhibitor PT, prothrombin time T.bili, total bilirubin TDF, tenofovir disoproxiI fumarate TPV, tipranavir ULN, upper limit of normal ZDV, zidovudine. 

Cross-resistance Cross-resistance among Pis has been observed. Tipranavir had less than 4-fold decreased susceptibility against 90% (94 of 105) of HIV-1 isolates resistant to amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, or saquinavir. Tipranavir-resistant viruses that emerged in vitro had decreased susceptibility to the Pis amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, and ritonavir but remained sensitive to saquinavir. 

Etravirine Delavirdine, efavirenz, lopinavir/ritonavir, nevirapine, ritonavir, tipranavir Darunavir, saquinavir, tenofovir... 

Fosamprenavir Abacavir, atazanavir, delavirdine, etravirine, indinavir, lopinavir, ritonavir, tipranavir, zidovudine Didanosine, efavirenz, nevirapine, saquinavir... 

Saquinavir Atazanavir, delavirdine, indinavir, lopinavir, nelfinavir, tenofovir Efavirenz, nevirapine, tipranavir... 

Nevirapine is a moderate inducer of CYP3A metabolism, resulting in decreased levels of amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone (Table 49-4). Drugs that induce the CYP3A system, such as tipranavir, rifampin, rifabutin, and St. John s wort, can decrease levels of nevirapine, whereas those that inhibit CYP3A activity, such as fluconazole, ketoconazole, and clarithromycin, can increase nevirapine levels. 

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... 

PROTEASE INHIBITORS ANTIHISTAMINES-ASTEMIZOLE, CHLORPHENAMINE, TERFENADINE Possibly t adverse effects with amprenavir, atazanavir, indinavir, ritonavir (with or without lopinavir), saquinavir and tipranavir Inhibition of CYP3A4-mediated metabolism of astemizole the risk is greatest in patients who are slow CYP2D6 metabolizers because chlorphenamine and terfenadine are also metabolized by this route Avoid co-administration... 

TIPRANAVIR + RITONAVIR LOPINAVIR + RITONAVIR Possibly 1 efficacy Significant i bioavailability Avoid co-administration... 

Clinically important, potentially hazardous interactions with amisulpride, amprenavir, atazanavir, celiprolol, ciprofloxacin, enoxacin, epirubicin, fosamprenavir, gatifloxacin, lomefloxacin, lopinavir, mistletoe, moxifloxacin, nilotinib, norfloxacin, ofloxacin, quinolones, ritonavir, sparfloxacin, tipranavir... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Clinically important, potentially hazardous interactions with amiodarone, atazanavir, azithromycin, bosentan, ciprofibrate, clarithromycin, clopidogrel, cyclosporine, darunavir, delavirdine, diltiazem, erythromycin, fosamprenavir, fusidic acid, gemfibrozil, grapefruit juice, imatinib, itraconazole, lopinavir, rabeprazole, ranolazine, red rice yeast, ritonavir, roxithromycin, selenium, St John s wort, tacrolimus, telithromycin, tipranavir, verapamil, warfarin... 

Antiviral drugs Atazanavir [139] Lopinavir [139] Ritonavir [139] Saquinavir [139] Tipranavir [139]... 

HIV Protease Inhibitors Saquinavir, Ritonavir, Indinavir, Nelfinavir, Amprenavir, Lopinavir, Atazanavir, Fosamprenavir, Tipranavir and Darunavir as Drugs against HIV Infection... 

Figure 5.4 Structures of marketed HIV protease inhibitors. Saquinivir (top left), ritonavir (top middle), indinavir (top right), nelfinavir (second row left), lopinavir (second row middle), tipranavir (second row right), atazanavir (third row left), darunavir (third row middle), fosamprenavir (third row right) and amprenavir (bottom).

Methadone serum levels can be reduced by amprenavir, nelfina-vir, lopinavir/ritonavir, saquinavir/ritonavir, tipranavir/ritona-vir, and possibly ritonavir. In addition, amprenavir levels may be reduced by methadone. No interaction appears to occur between methadone and indinavir, or possibly atazanavir or saquinavir, alone. 

Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir... 

Lamivudine metabolism does not involve the cytochrome P450 isoenzyme CYP3A4. Therefore it is unlikely that it will interact with drugs, such as the protease inhibitors, whieh are metabolised by this system. No pharmacokinetic interaction appears to oeeur between lamivudine and amprenavir, - atazanavir, -" indinavir, and nelfinavir. The manufacturer of lopinavir/ritonavir notes that lamivudine did not alter the pharmacokinetics of lopinavir, - and tipranavir plus low-dose ritonavir did not cause a signifieant ehange in the AUC of lamivudine. - ... 

The data on the effect of protease inhibitors on ketoconazole are more limited. Amprenavir caused a modest increase in ketoconazole levels, and the UK manufacturer of amprenavir suggests that no ketoeonazole dose adjustment is necessary with amprenavir alone, although the US manufacturer recommends increased monitoring for adverse effeets and states that a dose reduction may be needed in patients receiving ketoconazole in doses of more than 400 mg daily. However, a marked effect was seen for ritonavir alone and for ritonavir combined with darunavir, fosamprenavir, lopinavir, saquinavir and theoretically tipranavir. This may increase the adverse effects of ketoconazole. Most protease inhibitor manufacturers say that doses greater than 200 mg a day of ketoconazole are not recommended. Similarly, the UK manufacturers of ketoconazole and ritonavir say that a dose reduction of ketoconazole should be considered when it is given with ritonavir. ... 

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. 

Food increases the bioavailability of atazanavir, darunavir, lopinavir/ritonavir soft capsules and solution, nelfinavir, saquinavir (all formulations) and tipranavir, but decreases that of indinavir. Food only minimally affects the bioavailability of amprenavir, fosamprenavir, lopinavir/ritonavir tablets and ritonavir. Mixing ritonavir with enteral feeds does not affect the pharmacokinetics of 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. ... 

Various dual combinations of proteas e inhibitors have been tried, or are us ed, to boos t the levels and cons equently the efficacy of one of the proteas e inhibitors . Ritonavir is the mos t potent at boos ting levels of the other proteas e inhibitors , and current guidelines recommend the us e of low-dos e ritonavir in combination with atazanavir, darunavir, fos amprenavir, lopinavir, s aquina-vir, or tipranavir. Some proteas e inhibitor combinations may re-s ult in additive toxicity (indinavir and ritonavir or atazanavir). Although this monograph s ummaris es the pharmacokinetic interactions and dos ing recommendations current guidelines should be consulted when choosing protease inhibitor combinations. 

In a clinical study of dual-boosted protease inhibitor combination therapy in multiple-treatment experienced HIV-positive adults there was a 70% reduction in minimum lopinavir levels when tipranavir/ritonavir 500/200 mg twice daily was added to lopinavir/ritonavir 400/100 mg... 

Rifabutin bioavailability is increased by amprenavir, atazanavir, fosamprenavir/ritonavir, indinavir, lopinavir/ritonavir, nelfinavir, tipranavir/ritonavir, and especially ritonavir, with an increased risk of toxicity. Rifabutin modestiy decreases the bioavailability of indinavir, neifinavir, and particuiarly saquinavir (with an increased risk of therapeutic faiiure), but has no effect on amprenavir, atazanavir, and ritonavir-boosted fosamprenavir. The combination of rifabutin with protease inhibitors may be used, but dosage adjustments of rifabutin or both drugs are often necessary. 

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