Foods Amprenavir

Amprenavir. Food resulted in a 25% reduetion in the AUC of amprenavir, but no change in the steady-state trough level. Consequently, the manufae-turers say it ean be given with or without food, - but the US manufacturer says not with a high-fat meal. ... 

Amprenavir may be taken with or without food however, a high-fat meal decreases the absorption of amprenavir and should be avoided. Advise adult and pediatric patients not to take supplemental vitamin E since the vitamin E content of amprenavir capsules and oral solution exceeds the Reference Daily Intake (adults, 30 units pediatrics, approximately 10 units). 

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). 

In 1995 the FDA approved saquinavir, the first protease inhibitor, for use in combination with other nucleoside analogue medications. In 1999 a soft gel capsule formulation of saquinavir with considerably improved absorption characteristics was developed. Ritonavir and indinavir have been approved for use alone or in combination with nucleoside analogue medications in people with advanced HIV disease. Nelfinavir is the first protease inhibitor labeled for use in children. Amprenavir is the newest of the protease inhibitors. Amprenavir can be taken with or without food, but it should not be taken with a high-fat meal because the fat content may decrease the absorption of the drug. The most disturbing adverse reactions to protease inhibitors consist of the lipodystrophy syndrome with severe hyperlipidemia and unpredictable fat redistributions over the body... 

Amprenavir is rapidly absorbed from the gastrointestinal tract, and its prodrug can be taken with or without food. However, high-fat meals decrease absorption and thus should be avoided. The plasma half-life is relatively long (7-11 hours). Amprenavir is metabolized in the liver by CYP3A4 and should be used with caution in the setting of hepatic insufficiency. 

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... 

The oral absorption of amprenavir is rapid, and peak concentrations are reached between 1 and 2h administration of both amprenavir and fosamprenavir with food is not a concern. Fosamprenavir is dephosphorylated to amprenavir in intestinal mucosa. Amprenavir is 90% bound to plasma protein with most to ai-acid glycoprotein. It is metabolized by the cytochrome P-450 system, CYP3A4, in the liver, and more than 90% of the drug is excreted after its metabolism in feces. In combination with other antiretroviral agents, amprenavir/fosamprenavir are indicated for the treatment of HIV infection. 

Amprenavir is rapidly absorbed following oral administration and may be taken with or without food. High-fat meals decrease the absorption of the drug and, therefore, should be avoided. The product is available in capsule and liquid form. The recommended adult and adolescent dose of 1,200 mg twice... 

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. 

Fosamprenavir. The manufaeturer states that taking the fosamprenavir tablet formulation with a high-fat meal did not alter plasma amprenavir pharmacokineties (derived from fosamprenavir) when compared with taking this formulation in the fasted state. Fosamprenavir tablets may be taken without regard to food intake. ... 

The steady-state AUC of amprenavir was reduced by 32% when amprenavir 750 or 800 mg three times daily was given with saquinavir (soft gel capsule) 800 mg three times daily, and the maximum plasma level was reduced by 37%. In this study, the pharmacokinetics of saquinavir were not changed when compared with historical control data. In a model-based pharmacokinetic analysis of data from a clinical study, amprenavir intrinsic clearance was not altered by saquinavir, which agrees with in vitro data. It was suggested that, as amprenavir was given with food , (p.818), in the first study, this may have accounted for the reduced amprenavir levels. ... 

---