Amprenavir dosing

Amprenavir Rifabutin dose at least halved (150 mg daily or every other day, or 300 mg three times per week). Amprenavir dose unchanged. Not recommended (amprenavir levels markedly reduced). 1-3... 

Lalezari JP, DeJesus E, Northfelt DW, Richmond G, Wolfe P, Haubrich R, Henry D, Powderly W, Becker S, Thompson M, Valentine E, Wright D, Carlson M, Riddler S, Haas FF, DeMasi R, Sista PR, Salgo M, Delehanty J (2003a) A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in nonnucleoside reverse transcriptase inhibitor-naive HIV-infected adults. Antivir Ther 8 279-287... 

Adults The recommended oral dose of amprenavir capsules for adults is 1200 mg (eight 150 mg capsules) twice daily in combination with other antiretroviral agents. 

Capsules - Use with caution in patients with moderate or severe hepatic impairment. Patients with Child-Pugh scores ranging from 5 to 8 should receive a reduced dose of amprenavir capsules of 450 mg twice daily, and patients with a Child-Pugh score ranging from 9 to 12 should receive a reduced dose of amprenavir capsules of 300 mg twice daily. 

Hepatic function impairment Amprenavir is principally metabolized by the liver exercise caution when administering this drug to patients with hepatic impairment. Carcinogenesis Results showed an increase in the incidence of benign hepatocellular adenomas and an increase in the combined incidence of hepatocellular adenomas plus carcinoma in males of both species at the highest doses tested. 

Children Two hundred fifty-one patients 4 years of age and above have received amprenavir as single or multiple doses in studies. An adverse event profile similar to that seen in adults was seen in pediatric patients. The safety, efficacy, and pharmacokinetics of amprenavir capsules have not been evaluated in pediatric patients below 4 years of age. 

Monitoring Amprenavir, when used alone or in combination with low-dose ritonavir, has been associated with elevations of AST and ALT in some patients. Exercise caution when administering amprenavir to patients with hepatic impairment. Conduct P.1079... 

The combination of amprenavir and low-dose ritonavir has been associated with elevations of cholesterol and triglycerides, AST, and ALT in some patients. Consider appropriate laboratory testing prior to initiating combination therapy with amprenavir and ritonavir and at periodic intervals, or if any clinical signs or symptoms of hyperlipidemia or elevated liver function tests occur during therapy. 

Vitamin E Formulations of amprenavir provide high daily doses of vitamin E. Hemophilia There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. 

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). 

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... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

Dosage adjustments in comhination therapy Amprenavir. Amprenavir 1,200 mg and ritonavir 200 mg once a day or amprenavir 600 mg and ritonavir 100 mg twice a day. Am-penavirandefavirenz. Amprenavir 1,200 mg twice a day and ritonavir 200 mg twice a day with standard dose of efavirenz. Indinavir. Indinavir 800 mg twice a day and ritonavir 100-200 mg twice a day or indinavir400 mg twice a day and ritonavir 400 mg twice a day. Nelfinavirorsaquinavir. Ritonavir 400 mg twice a day. Rifabutin. Decrease rifabutin dosage to 150 mg every other day. 

Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Posse S, Taburet AM. Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice. Antimicrob Agents Chemother 2002 46(5) 1589-1590. 

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. 

Solutions of sodium hydroxide and/or diluted hydrochloric acid may have been added to adjust pH. Each milliliter of AGENERASE oral solution contains 46 U vitamin E in the form of TPGS. Propylene glycol is in the formulation to achieve adequate solubility of amprenavir. The recommended daily dose of AGENERASE oral solution of 22.5 mg/kg twice daily corresponds to a propylene glycol intake of 1650 mg/kg per day. 

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... 

In July 1995, Vertex (Cambridge/MA, USA) presented encouraging preclinical and phase I results for Agenerase (amprenavir,VX-478) the compound demonstrated no toxicity for single doses up to 1200 mg but 70-78% bioavailability in tablet form and a half-life of 8 h in blood plasma, in combination with a 25-fold decrease of viral count in comparison with the base case. Even versus the most resistant HIV strain, VX-478 is only 15-fold less sensitive than against an unmutated virus. 

Amprenavir PI 1200 mg bid Separate dosing from didanosine or antacids by 1 hour. Avoid high-fat meals. Rash, diarrhea, nausea See footnote 2 for concurrent drug contraindication s. Oral solution contraindicated in young children and pregnant women. 

Amprenavir [am PREN a veer] Like other protease inhibitors, amprenavir is used in combination with a least two nucleoside reverse transcriptase inhibitors. Its long plasma half-life permits twice daily dosing, but the large size and number of capsules per day (16) day may reduce patient compliance. The drug may be less well tolerated than some other protease inhibitors and it is unclear whether amprenavir offers any clinical advantages over other protease inhibitors. 

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