Fosamprenavir Esomeprazole

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Proton pump inhibitors (marked effect) and H2-receptor antagonists (modest effect) reduce atazanavir levels. Other drugs that increase gastric pH are also predicted to reduce plasma levels of atazanavir. Fosamprenavir may be similarly affected (moderate effects seen with ranitidine), although antacids and esomeprazole had little effect in one study. Omeprazole decreases indinavir levels and an antacid modestly decreased tipranavir levels. Neither ranitidine nor omeprazole had any effect on darunavir/ritonavir or lopinavir/ritonavir levels. In contrast, cimetidine, ranitidine and omeprazole have been shown to increase saquinavir levels. 

In contrast, esomeprazole 20 mg once daily had no effect on the steady-state pharmacokinetics of amprenavir after either fosamprenavir 1.4 g... 

Based on the limited data with other protease inhibitors, the manufacturer of amprenavir also recommends it should not be given within 1 hour of antacids. The decrease in amprenavir levels seen when fosamprenavir is given with an antacid are not considered clinically relevant, and no fosamprenavir dose adjustments are likely to be neeessary. Greater decreases were seen with ranitidine, although the minimum levels were unehanged. The UK manufaeturer states that no fosamprenavir dose adjustment is needed with ranitidine or other H2-receptor antagonists however, the US manufacturer says the combination should be used with caution because fosamprenavir may be less effective. However, no interaction occurred with esomeprazole, and this, or other proton pump inhibitors may be given at the same time as fosamprenavir. 

Kiser JJ, Lichtenstein Anderson PL, Fletcher CV. Effects of esomeprazole on the pharmacokinetics of atazanavir and fosamprenavir in a patient with human immunodeficiency virus infection. Pharmacodierapy (200Q 26, 511-14. 

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