Proton pump Atazanavir

Drugs that may affect atazanavir include the following antacids and buffered medications, clarithromycin, didanosine (buffered formulation only), efavirenz, H2-receptor antagonists, indinavir, itraconazole, ketoconazole, nevirapine, proton pump inhibitors, rifampin, ritonavir, St. John s wort, tenofovir, voriconazole. 

ATAZANAVIR PROTON PUMP INHIBITORS Possibly 1 efficacy of atazanavir i plasma concentration uncertain cause Avoid co-administration... 

PROTON PUMP INHIBITORS ATAZANAVIR, NELFINAVIR i plasma levels of atazanavir and nelfinavir with esomeprazole, and t risk of therapeutic failure of the antiviral agent Uncertain possibly due to enzyme induction Avoid co-administration... 

Atazanavir Atazanavir is a peptide protease inhibitor that is active against both HlV-1 and HlV-2. Absorption is increased by food and it is recommended that the drug be administered with a meal. Absorption may be pH dependent, because proton pump inhibitors substantially reduce drug concentration after oral dosing. Like indinavir, atazanavir frequently causes unconjugated hyperbilirubinemia. The drug may be less likely than other HIV protease inhibitors to cause lipodystrophy. 

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. 

Proton pump inhibitors. The AUC of atazanavir was reduced by 76% and the trough plasma level by 78% when atazanavir/ritonavir 300/100 mg was given with omeprazole 40 mg. Increasing the dose of atazanavir/ritonavir to 400/100 mg did not negate the effects of this interaction. An even greater effect (94% reduction in AUC) was seen when atazanavir alone was given with omeprazole, and the same effect was seen with lansoprazole. Similar results were found in another study with omeprazole ritonavir levels were not affected. ... 

Atazanavir trough levels were significantly lower in patients taking proton pump inhibitors than in those taking H2-receptor antagonists in another studyA 65-year-old HIV-positive man had a marked reduction in atazanavir trough levels and AUC in a 12-hour study while receiving esomeprazole and atazanavir/ritonavir. ... 

Bristol-Myers Squibb Company. Re Reyataz (atazanavir sulfate) with or without Norvir (ritonavir) and proton pump inhibitors should not be coadm inister important new pharmacokinetic data, December 2004. Available at htq> //www. fda.gov/oashi/aids/listserv/ 2004/reyataz.pdf (accessed 21/08/07). 

Khanlou H, Farthing C. Co-administration of atazanavir with proton-pump inhibitors and H2 blockers. J Acqidr Immune Defic Syndr (2005) 39,503. 

Sahloff EG, Duggan JM. Chnic outcomes associated with concomitant use of atazanavir and proton pump inhibitors. Ann Pharmacodier (2006) 40,1731 -6. 

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