Ritonavir Fosamprenavir

Therapy-naive patients Fosamprenavir 1400 mg twice daily (without ritonavir) fosamprenavir 1400 mg once daily plus ritonavir 200 mg once daily fosamprenavir 700 mg twice daily plus ritonavir 100 mg twice daily. 

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... 

Ritonavir Fosamprenavir, delavirdine, efavirenz, indinavir Didanosine, tenofovir, zidovudine... 

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

Atazanavir or fosamprenavir or nelfinavir or saquinavir/ ritonavir, and zidovudine or stavudine or tenofovir or abacavir or didanosine, and lamivudine or emtricitabine... 

Fosamprenavir (fAPV) Lexiva 700-mg tabs ARV-na ive pts fAPV 1,400 mg bid or fAPV 700 mg + RTV 1 00 mg bid PS-experienced pts fAPV 700 mg + RTV 1 00 mg bid Co-admin is tra tion w/EFV fAPV 700 mg + RTV 1 00 mg bid or fAPV 1400 mg + RTV 300 mg qday Child-Pugh Dose Class 5-8 700 mg bid 9-12 Not recommended Ritonavir should not be used in patients with hepatic impairment None Skin rash diarrhea, nausea and vomiting headache hyperlipidemia LFT elevation hyperglycemia fat maldistribution increased bleeding episodes in patients with hemophilia CYP3A4 inhibitor, inducer, and substrate... 

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). 

Ritonavir dose adjustment when fosamprenavir plus ritonavir are administered with efavirenz An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz is administered with fosamprenavir plus ritonavir once daily. 

Hepatic function impairment Reduce fosamprenavir dose to 700 mg twice daily, in patients with mild or moderate hepatic impairment (Child-Pugh score ranging from 5 to 8) receiving fosamprenavir without concurrent ritonavir. Do not use fosamprenavir in patients with severe hepatic impairment (Child-Pugh score ranging from 9 to 12). 

If fosamprenavir is coadministered with ritonavir, the antiarrhythmic agents flecainide and propafenone also are contraindicated. 

Hepatic function impairment Exercise caution when administering fosamprenavir to patients with hepatic impairment. Patients with impaired hepatic function receiving fosamprenavir without concurrent ritonavir may require dose reduction. 

Lipid elevations Treatment with fosamprenavir plus ritonavir has resulted in increases in the concentration of triglycerides. 

The potential for drug interactions with fosamprenavir changes when fosamprenavir is coadministered with the potent CYP3A4 inhibitor ritonavir. Because ritonavir is a CYP2D6 inhibitor, clinically significant interactions with drugs metabolized by CYP2D6 are possible when coadministered with fosamprenavir plus ritonavir. 

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

Concurrent therapy with efavirenz PO In patients receiving fosamprenavir plus once-daily ritonavir in combination with efavirenz, an additional 100 mg/day ritonavir (300 mg total/day) should be given. 

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... 

Tipranavir PI2 Must be taken with ritonavir to achieve effective levels tipranavir 500 mg bid/ritonavir 200 mg bid. Avoid use in hepatic insufficiency. Approved for pediatric usage Take with food. Separate from ddl by at least 2 h. Avoid antacids. Avoid in patients with sulfa allergy. Refrigeration required Diarrhea, nausea, vomiting, abdominal pain, rash, t liver enzymes, hypercholesterolemia, hypertriglyceridemia See footnote 4 for contraindicated medications. Avoid concurrent fosamprenavir, saquinavir. Do not administer to patients at risk for bleeding... 

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... 

Fosamprenavir is a prodrug of amprenavir that is rapidly hydrolyzed by enzymes in the intestinal epithelium. Because of its significantly lower daily pill burden, fosamprenavir tablets have replaced amprenavir capsules for adults. Fosamprenavir is most often administered in combination with low-dose ritonavir. 

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. 

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... 

Alternative regimen Nevirapine Atazanavir Fosamprenavir Fosamprenavir + ritonavir Fopinavir/ ritonavir Abacavir/ lamivudine Didanosine/ lamivudine... 

Arvieux, C., and Tribut, O. Amprenavir or fosamprenavir plus ritonavir in HIV infection Pharmacology, efficacy and tolerability profile. Drugs 65(5) 633-659, 2005. 

A Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice", verapamil Cimetidine... 

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