Omeprazole Atazanavir

Drugs that may affect indinavir include didanosine, aldesleukin, anticonvulsants, atazanavir, nelfinavir, nevirapine, omeprazole, rifapentine, ritonavir, clarithromycin, azole antifungals, rifamycins, delavirdine, efavirenz, St. John s wort. 

Atazanavir PI2 400 mg daily or 300 mg daily with ritonavir 100 daily. Adjust dose in hepatic insufficiency Take with food. Separate dosing from ddl or antacids by 1 h. Separate dosing from cimetidine and other acid-reducing agents by 12 h Nausea, vomiting, diarrhea, abdominal pain, headache, peripheral neuropathy, skin rash, indirect hyperbilirubinemia, prolonged PR and/or QTC interval See footnote 4 for contraindicated medications. Also avoid indinavir, irinotecan, and omeprazole. Avoid in severe hepatic insufficiency... 

As an inhibitor of CYP3A4 and CYP2C9, the potential for drug-drug interactions with atazanavir is great (Tables 49-3 and 49-4). Atazanavir AUC is reduced by 76% when combined with omeprazole thus, the combination is to be avoided. In addition, co-administration of atazanavir with other drugs that inhibit UGT1A1, such as indinavir and irinotecan, is contraindicated because of enhanced toxicity. Tenofovir and efavirenz should not be -administered with atazanavir unless ritonavir is added to boost levels. 

Drugs that may inhibit cytochrome P450 metabolism of other drugs include amiodarone, androgens, atazanavir, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cyclosporine, delavirdine, diltiazem, diphenhydramine, disulfiram, enoxacin, erythromycin, fluconazole, fluoxetine, fluvoxamine, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, mexile-tine, miconazole, nefazodone, omeprazole, paroxetine, propoxyphene, quinidine, ritonavir, sulfamethizole, verapamil, voriconazole, zafirlukast, and zileuton. 

Allergic interstitial nephritis Penicillins, rifampin, sulfonamides, thiazides, cimetidine.phenytoin, allopurinol, furosemide, NSAIDS, ciprofloxacin, pantoprazole, omeprazole, atazanavir, bevacizumab Rash, fever, eosinophilia, eosinophiluria, pyuria... 

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. ... 

The UK manufacturer of indinavir states that a normal (acidic) gastric pH may be necessary for optimum absorption of indinavir. Any drug that increases the gastric pH could therefore potentially reduce absorption. Altered gastric pH may also account for the interaction with atazanavir. Cimetidine probably boosts saquinavir levels by inhibiting the first-pass metabolism of saquinavir. It is not understood why ranitidine and omeprazole increase saquinavir levels. 

Chan-Tack KM, Edozien A. Ritonavir-boosted atazanavir may be efficacious inHIV-infect-ed patients concurrently receiving omeprazole. Clin Infect Dis (2006) 42, 1344. 

Omeprazole In previous studies coadministration with omeprazole 40 mg/day significantly reduced atazanavir exposure... 

Zhu L, Persson A, Mahnke L, Eley T, Li T, Xu X, Agarwala S, Dragone J, Bertz R. Effect of low-dose omeprazole (20 mg daily) on the pharmacokinetics of multiple-dose atazanavir with ritonavir in healthy subjects. J Clin Pharmacol 2011 51(3) 368-77. 

Fig. 22.6 a Dissolution curves of free ATV and loaded ATY into different mesoporous structures (simulated Intestine fluid, SIF, performed under sink conditions), b Kinetic release curve of different particles to SIF ratio. Varied amount of NFM-l-ATV was added into 500mL SIF, respectively, corresponding to a series of particles-to-SlF ratio 20, 40, 80 and 160mg/L. c ATV plasma concentration, Sprague Dawley rats were administered with Omeprazole (lOOmg/kg) 8 h prior to the administration of free atazanavir and NFM-1 Silica loaded with atazanavir (lOmg/Kg)... 

---