Amprenavir drug interactions

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

Drug interactions Serious and/or life-threatening drug interactions could occur between amprenavir and amiodarone, lidocaine (systemic), tricyclic antidepressants, and quinidine. Concentration monitoring of these agents is recommended if these agents are used concomitantly with amprenavir. 

Decker CJ, Laitinen LM, Bridson GW, Raybuck SA, Tung RD, Chaturvedi PR. Metabolism of amprenavir in liver microsomes role of CYP3A4 inhibition for drug interactions. J Pharm Sci 1998 87(7) 803-7. 

Khanlou H, Graham E, Brill M, Farthing C. Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy. AIDS 2002 16(5) 797-8. 

PI Protease inhibitors amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir Also note additional drug interactions above. 

Fluconazole inhibits CYP3A4 and CYP2C9 and thus significantly increases plasma concentrations of amprenavir, cisapride, cyclosporine, phenytoin, sulfonylureas, tacrolimus, theophylline, telithromycin, and warfarin. Patients receiving >400 mg daily or azotemic patients may experience additional drug interactions. Rifampin decreases the fluconazole AUC by -25%. 

Falloon J, Piscitelli S, Vogel S, Sadler B, Mitsuya H, KavUck MF, Yoshimura K, Rogers M, LaFon S, Manion DJ, Lane HC, Masur H. Comhination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV) infected patients failing a protease-inhibitor regimen pharmacokinetic drug interactions and antiviral activity. Clin bfect Dis (2000) 30, 313-18. 

Decker CJ,LaitinenLhlBridsai GW, RaybuckS./ Tui RD, Qiaturvedi PR. Metabolism of amprenavir in hver microsomes role of CYP3A4 inhibiticn for drug interactions. JPharm... 

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... 

Drug-drug transport interactions are important in combinationtherapy with HIV protease inhibitors (117). Many protease inhibitors are substrates for and inhibitors of CYP3A4 and P-gp. Different combination effects (e.g./ intrinsic clearance of amprenavir is reduced by nelfinavir and indinavir but not saquinavir) depend on the extent to which one or both of these enzymes are affected. 

A pharmacokinetic model has been developed to describe the interaction of amprenavir with ritonavir (6). A two-compartment linear model with first-order absorption fitted the amprenavir data best, while a one-compartment model best described the ritonavir data. Inhibition of the ehmination of amprenavir by ritonavir was modelled with an Emax inhibition model. Simulation of drug regimens based on the model suggested that in patients who fail to respond to a traditional amprenavir regimen, amprenavir 600 mg plus ritonavir 100 mg bd would produce similar Cmii, ICso ratios to amprenavir 1200 mg bd alone. 

Lamivudine metabolism does not involve the cytochrome P450 isoenzyme CYP3A4. Therefore it is unlikely that it will interact with drugs, such as the protease inhibitors, whieh are metabolised by this system. No pharmacokinetic interaction appears to oeeur between lamivudine and amprenavir, - atazanavir, -" indinavir, and nelfinavir. The manufacturer of lopinavir/ritonavir notes that lamivudine did not alter the pharmacokinetics of lopinavir, - and tipranavir plus low-dose ritonavir did not cause a signifieant ehange in the AUC of lamivudine. - ... 

Despite the increases in saquinavir levels, the UK manufacturer says that no dose adjustment is needed when saquinavir is given with erythromycin. The UK manufacturer of nelfinavir suggests that an interaction with erythromycin is unlikely, although it cannot be excluded. The UK manufacturer of ritonavir suggests that because erythromycin levels may rise, due to inhibition of its metabolism by ritonavir, care should be taken if both drugs are given. " It would seem prudent to monitor for erythromycin adverse effects. A similar warning has been issued by the UK manufacturer of amprenavir about the use of erythromycin. ... 

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