Lopinavir Fosamprenavir

Drug Exerting E ect Saquinavir Indinavir Ritonavir Nelfinavir Amprenavir Fosamprenavir Lopinavir Atazanavir... 

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. ... 

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. 

Amprenavir and atazanavir, given alone increase the levels of ethinylestradiol and norethisterone. Ritonavir and nelfinavir, in contrast to the effect that would normally be expected decrease the levels of ethinylestradiol. Reduced ethinylestradiol and norethisterone levels occur with fosamprenavir, lopinavir and ti-pranavir given with ritonavir. Indinavir does not appear to interact. 

Although information is limited, the pharmacokinetic interaction between the ethinylestradiol component of combined hormonal contraceptives and nelfinavir or ritonavir appears to be established and is likely to be clinically important. Similar decreases in plasma levels of ethinylestradiol caused by other drugs have resulted in reduced efficacy and reliability of combined oral contraceptives, and one retrospective report suggests that this has occurred with nelfinavir. It seem likely that the reduced contraceptive levels seen with fosamprenavir, lopinavir and tipranavir were due to the concurrent use of ritonavir (as would be common in practice). Similarly, although no interaction was reported with saquinavir, and raised contraceptive steroid levels were reported with amprenavir and atazanavir, in practice these drugs would be given with ritonavir (as a pharmacokinetic enhancer), and so the levels of combined hormonal contraceptives can reasonably be expected to be reduced. The Faculty ofFamily Planning... 

A number of other protease inhibitors (Fig. 23.16) have been developed in the last few years with the aim of improving pharmacokinetic profile. One of the first of these was amprenavir, which does not contain peptide bonds which slows down its clearance from the body. Its pharmokinetics are further improved when it is administered as its phosphate prodmg fosamprenavir. Lopinavir was also developed to give improved pharmacokinetics. Its effectiveness is improved by co-administration with... 

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

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

Fewer head-to-head data with oncedaily fosamprenavir-ritonavir and lopinavir ritonavir, as well as saquinavir (Invirase) + ritonavir... 

Current recommendations for treating HIV infection advocate a minimum of three antiretroviral agents. The typical regimen consists of two NtRTIs and either a ritonavir-boosted PI or NNRTI. The dual NtRTI backbone should include tenofovir plus emtricitabine (coformulated as Truvada) or zidovudine plus lamivudine (coformulated as Combivir). Abacavir plus lamivudine is an alternative. Recommended initial NtRTIs include atazana-vir-ritonavir, lopinavir-ritonavir, or fosamprenavir-ritonavir. Efavirenz is the recommended NNRTI except for women who plan to become pregnant or who do not have adequate contraception. 

Concomitant therapy with efavirenz, nevirapine, fosamprenavir, or nelfinavir-Consider a dose increase to 533/133 mg lopinavir/ritonavir (4 capsules or 6.5 mL) twice daily taken with food when used in combination with efavirenz, nevirapine, amprenavir, or nelfinavir, or 600/150 mg (3 tablets) twice daily with or without food when used in combination with efavirenz, nevirapine, fosamprenavir without ritonavir, or nelfinavir in treatment-experienced patients where decreased susceptibility to lopinavir is clinically suspected (by treatment history or laboratory evidence). 

Fosamprenavir plus ritonavir may interact with flecainide, propafenone, efavirenz plus ritonavir, and lopinavir plus ritonavir. Efavirenz may affect fosamprenavir with or without ritonavir. 

Similar labeling language also in the labeling of INVIRASE (Roche Laboratories) (saquinavir mesylate) capsules, December 2003 KALETRA (Abbott) (lopinavir/ritonavir) capsules, (lopinavir/ritonavir) oral solution, February 2004 and LEXIVA (GlaxoSmithKline) (fosamprenavir calcium) tablets. May 2004. 

Fosamprenavir PI2 1400 mg bid or 700 mg bid with ritonavir 100 bid or 1400 mg daily with ritonavir 100-200 mg daily. Adjust dose in hepatic insufficiency Separate dosing from antacids by 2 h. Avoid concurrent high-fat meals Diarrhea, nausea, vomiting, hypertriglyceridemia, rash, headache, perioral paresthesias, t liver enzymes See footnote 4 for contraindicated medications. Do not administer with lopinavir/ritonavir or in severe hepatic insufficiency. Also avoid cimetidine, disulfiram, metronidazole, vitamin E, ritonavir oral solution, and alcohol when using the oral solution... 

Lopinavir/ritonavir PI/PI2 400 mg/100 mg bid or 800 mg/200 mg daily. May need dose adjustment in hepatic insufficiency Take with food. Separate dosing from ddl by 1 h. Store capsules and solution in refrigerator Diarrhea, abdominal pain, nausea, hypertriglyceridemia, headache, t liver enzymes, See footnote 4 for contraindicated medications. Also avoid fosamprenavir. Avoid disulfiram and metronidazole with oral solution... 

Delavirdine Fosamprenavir, didanosine, lopinavir, nelfinavir, ritonavir... 

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

Lopinavir Delavirdine, indinavir, ritonavir, darunavir Fosamprenavir, efavirenz, nelfinavir, nevirapine, tenofovir... 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

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

Taltobulin, 11 Tamibarotene, 76 Tandutinib, 183 Tanomastat, 47 Tezacitabine, 131 Tipifamib, 172 Topixantrone, 227 Troxacitabine, 131 Vandetanib, 181 Antipsoriatic Ecalcidine, 38 Antiviral Amdoxovir, 199 Amprenavir, 4 Aplaviroc, 134 Atazanavir, 7 Capravirine, 95 Clevudine, 130 Daninavir, 5 Efavirenz, 177 Emivirine, 123 Emtricitabine, 132 Etravirine, 123 Fosamprenavir, 6 Lopinavir, 7 Maraviroc, 107 Maribavir, 158 Omaciclovir, 199 Oseltamivir, 25 Peramavir, 53 Rupinavir, 9 Tenofovir, 197 Tiprinavir, 120 Anxiolytic Sunepitron, 209 Apetite Supressant Rimonabant, 99 Cardiotonic Naxifylline, 203 Torborinone, 172 Collagenase Inhibitor Cipemastat, 99 Diuretic Lixivaptan, 222 Tolvaptan, 186 Elastase Inhibitor Sivelstat, 54... 

This class of agents affects a later part of the HIV cycle, by inhibiting the protease enzyme and leading to impaired assembly of mature HIV virions. Examples include amprenavir, atazanavir, darunavir, fosampre-navir indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir. There have been no published reports of AKI or other direct kidney toxicity due to amprenavir, darunavir, fosamprenavir, and lopinavir. 

Clinically important, potentially hazardous interactions with azithromycin, bosentan, ciprofibrate, clarithromycin, clopidogrel, cyclosporine, erythromycin, fosamprenavir, fusidic acid, gemfibrozil, imatinib, itraconazole, lopinavir, niacin, quinine, red rice yeast, telithromycin, verapamil... 

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 acetylcysteine, adenosine, aprepitant, aripiprazole, buprenorphine, caffeine, charcoal, clarithromycin, clobazam, dorazepate, clozapine, darunavir, dasatinib, delavirdine, dexamethasone, diltiazem, doxacurium, erythromycin, felodipine, fesoterodine, fosamprenavir, imatinib, influenza vaccines, lacosamide, lapatinib, levetiracetam, lopinavir, methylprednisolone, midazolam, nelfinavir, nilotinib, piracetam, prednisolone, propoxyphene, ritonavir, rivaroxaban, rufinamide, solifenacin, St John s wort, telithromycin, temsirolimus, terbinafine, tolvaptan, troleandomycin, verapamil, voriconazole... 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

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, anisindione, anticoagulants, azithromycin, corticosteroids, cyclosporine, dapsone, delavirdine, dicumarol, fosamprenavir, lapatinib, lopinavir, midazolam, oral contraceptives, ritonavir, solifenacin, tacrolimus, temsirolimus, tolvaptan, voriconazole... 

ABBREVIATIONS EFV, efavirenz 3TC, lamivudine AZT, zidovudine TDF, tenofovir disoproxil fumarate d4T, stavudine LPV/r, lopinavir/ritonavir coformulation FTC, emtricitabine NVP, nevirapine ddl, didanosine ATV, atazanavir fosAPV, fosamprenavir RTV, ritonavir IDV, indinavir NFV, nelfinavir SQV, saquinavir. 

PI disables protease, a protein that HIV needs to make more copies of itself. Drugs within this category include Amprenavir (Agenerase, APV), Atazanavir (Reyataz, ATV), Fosamprenavir (Lexiva, FPV), Indinavir (Crixivan, IDV), Lopinavir, Ritonavir (Kaletra, LPV/r), Nelvinavir (ViracepL NFV), Ritonavir, (Norvir, RTV), and Saquinavir (Fortovase, SQV Invirase). 

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).

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