Omeprazole Indinavir

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... 

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. 

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. 

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. 

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. 

Hugen PWH, Burger DM, ter Hofstede HJM, Koopmans PP. Concomitant use of indinavir and omeprazole risk of antiretroviral subtherapy. AIDS (1998) 12 (Suppl 4), S29. 

Burger DM, Hugen PWH, Kroon FP, Groeneveld P, Brinkman K, Foudraine NA, Sprenger H, Koopmans PP, Hekster YA. Pharmacokinetic interaction between the proton pump inhibitor omeprazole and the HIV protease inhibitor indinavir. AIDS (1998) 12, 2080-2. 

Rublein JC, Donovan BJ, Hollowell SB, Min SS, Theodore D, asch RH, Kashuba ADM. Effect of omeprazole on the plasma concentrations of indinavir in HIV-negative subjects. Intersci Conf Antimicrob Agents Chemother (2003) 43, 35. 

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