Omeprazole Ritonavir

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. ... 

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. 

Tipranavir both inhibits and induces the CYP3A4 system. When used in combination with ritonavir, its net effect is inhibition. Tipranavir also induces P-glycoprotein transporter and thus may alter the disposition of many other drugs (Table 49-4). Concurrent administration of tipranavir with fosamprenavir or saquinavir should be avoided owing to decreased blood levels of the latter drugs. Tipranavir/ritonavir may also decrease serum levels of valproic acid and omeprazole. Levels of lovastatin, simvastatin, atorvastatin, and rosuvastatin may be increased, increasing the risk for rhabdomyolysis and myopathy. 

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. 

Isoniazid Avasimibe Bosentan Carbam- a2epine" Clotrimazole Cyproterone acetate Hyperforin Lovastatin Mifepristone Nelfinavir Nifedipine Omeprazole Paclitaxel Phenobarbital Phenytoin Rifabutin Rifampin"" Rifapentine Ritonavir Simvastatin Sulfinpyrazole Topotecan Troglitazone Troleandomycin Vitamin E Vitamin K2 Yin zhi wuang... 

INDINAVIR OMEPRAZOLE Possibly 1 efficacy of indinavir i plasma concentration uncertain cause t dose of indinavir from 800 mg three times a day to 1 g three times a day, or preferably add ritonavir 200 mg once daily... 

Ajmaline, alprenolol, amiflamine, amphetamine, aprindine, captopril, chlorpheniramine, cinnarizine, citalopram, clomipramine, clozapine, codeine, desipramine, dolasteron, encainide, flecainide, fluoxetine, fluphenazine, haloperidol, hydrocordone, imipramine, loratidine, methoxyphenamine, 3,4-methylenedioxymethamphetamine, metoprolol, mexiletine, (S)- and (i )-mianserin, nifedipine, olanzapine, omeprazole, oxycodone, perhexiline, phenformin, propaphenone, propranolol, remoxipride, ritonavir, saquinavir, selegiline, tamsulosin, timolol, tomoxetine, tramadol, trifluperidol, zolpidem... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

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 a crossover study in 16 healthy subjects, neither omeprazole 20 mg daily nor ranitidine 150 mg twice daily had a significant effect on the AUC or minimum level of darunavir after darunavir/ritonavir 400/100 mg was given twice daily for 5 days. ... 

In a randomised study in healthy subjects, omeprazole 40 mg once daily or ranitidine 150 mg one hour before breakfast had no effect on the relative bioavailability of either lopinavir or ritonavir when lopinavir/ritonavir 800/200 mg once daily was taken 30 minutes after breakfast, or when lopinavir/ritonavir 400/100 mg twice daily (30 minutes after a meal) was given 1.5 hours after the acid-reducing drug. The lopinavir/ritonavir was taken in a tablet form. ... 

Omeprazole 40 mg daily increased the AUC of saquinavir by 82% when saquinavir/ritonavir 1000/100 mg was given twice daily to 18 healthy subjects. ... 

The interaction between omeprazole and indinavir would appear to be established. Omeprazole should probably not be used with indinavir unless ritonavir is used to boost the indinavir levels. This would likely apply to other proton pump inhibitors used with indinavir as well. 

Omeprazole and ranitidine do not appear to alter the pharmacokinetics of darunavir/ritonavir or lopinavir/ritonavir. 

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

Sekar VJ, Lefebvre E, De Paepe E, De Marez T, De Pauw M, Parys W, Hoetehnans RM. Pharmacokinetic interaction between darunavir boosted with ritonavir and omeprazole or ranitidine in human immunodeficiency virus-negative healthy volunteers. Antimicrob Agents Chemodter (p.007) 51, 958-61. 

Winston A, Back D, Fletcher C, Robinson L, Unsworth J, Tolowinska I, Schutz M, Pozniak AL, Gazzard B, Boffito M. Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers. AIDS (2006) 20, 1401-6. 

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