Fosamprenavir

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

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. 

The example of amprenavir, an HIV-1 protease inhibitor, shows that intestinal metabolism can also be used as a strategy to enhance the bioavailability of compounds. In the biopharmaceutics classification system (BCS), amprenavir can be categorized as a class II compound it is poorly soluble but highly permeable [51]. Fosamprenavir, the water-soluble phosphate salt of amprenavir, on the other hand, shows poor transepithelial transport. However, after oral administration of fosamprenavir, this compound is metabolized into amprenavir in the intestinal lumen and in the enterocytes mainly by alkaline phosphatases, resulting in an increased intestinal absorption [51, 174],... 

Wire MB, Shelton MJ, Studenberg S (2006) Fosamprenavir Clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet 45 137-168. 

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). 

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. 

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). 

Pharmacology Fosamprenavir is a prodrug of amprenavir, an inhibitor of HIV protease. 

Absorption/Distribution - Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by enzymes in the gut epithelium as it is absorbed. After administration of a single dose of fosamprenavir to HIV-1-infected patients, the... 

Metabolism/Excretion- Fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. 

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

Skin reactions Severe or life-threatening skin reactions, including Stevens-Johnson syndrome, were reported in less than 1% of patients treated with fosamprenavir in the clinical studies. Discontinue treatment with fosamprenavir for severe or life-threatening rashes and moderate rashes accompanied by systemic symptoms. Hemolytic anem/a.-Acute hemolytic anemia has been reported. 

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. 

Children The safety and efficacy of fosamprenavir have not been established in pediatric patients. 

Sulfa sensitivity Use fosamprenavir with caution in patients with a known sulfonamide allergy. Fosamprenavir contains a sulfonamide moiety. 

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

Resistance/Cross-resistance Because the potential for HIV cross-resistance among PI has not been fully explored, it is unknown what effect therapy with fosamprenavir will have on the activity of subsequently administered PI. 

CYP3A4 Amprenavir is metabolized by CYP3A4 and is an inhibitor (and possibly an inducer) of CYP3A4. Coadministration of fosamprenavir and drugs that induce CYP3A4, such as rifampin, may decrease amprenavir concentrations and reduce its therapeutic effect. Coadministration of fosamprenavir and drugs that inhibit CYP3A4 may increase amprenavir concentrations and increase the incidence of adverse effects. 

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. 

Drugs that may be affected by fosamprenavir include the following Amiodarone, amitriptyline, benzodiazepines, calcium channel blockers, cisapride, contraceptives (oral), cyclosporine, ergot derivatives, HMG-CoA reductase inhibitors, imipramine, itraconazole, ketoconazole, lidocaine (systemic), methadone, pimozide, quinidine, rifabutin, sildenafil, tacrolimus, vardenafil, warfarin. 

Drugs that may affect fosamprenavir include antacids, carbamazepine, delavirdine, dexamethasone, histamine H2-receptor antagonists, HMG-CoA reductase inhibitors,... 

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

Abacavir (Ziagen) Amprenavir (Agenerase) Delavirdine (Rescriptor) Didanosine [ddl] (Videx) Efavirenz (Sustiva) Efavirenz/Emtricitabine/ Tenofovir (Atripla) Fosamprenavir (Lexiva)... 

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