Indinavir Diltiazem

Antibacterials Ciprofloxacin Erythromycin Isoniazid Antidepressants Flnoxetine Huvoxamine Paroxetine Antifungal drugs Fluconazole Itraconazole Ketoconazole Miconazole Antiviral drugs Indinavir Ritonavir Saquinavir Cardiovascular drugs Amiodarone Diltiazem Quinidine Verapamil... 

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. 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

A Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice", verapamil Cimetidine... 

Acyclovir Erythromycin Ivermectin Itraconazole Rifampin Actinomycin D Daunorubicin Doxorubicin Docetaxel Epirubicin Etoposide Imatinib Irinotecan Paclitaxel Vinblastine Vincristine Amprenavir Indinavir Nelfinavir Ritonavir Saquinavir Cyclosporine A Tacrolimus Digoxin Quinidine Verapamil Diltiazem Aldosterone Cortisol Corticosterone Dexamethasone Hydrocortisone Cyclosporine Metkephamid Enkephalin... 

HIV protease inhibitors Indinavir Nelfinavir Ritonavir Saquinavir Amiodarone not Azithromycin Cimetidme Clarithromycin . Diltiazem Erythromycin Fluoxetine Fluvoxamine Grapefruit Juice Itraconazole Ketoconazole Mibefradil Nefezodone Troleandomydn Verapamil... 

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... 

Symptomatic orthostasiisi occurred in a patient taking nelfinavir or ritonavir/indinavir and nifedipine. Another patient had similar symptoms when nelfinavir was added to felodipine therapy. Atazanavir markedly increased diltiazem bioavailability with an increase in cardiac effects in healthy subjects. Similarly, ritonavir/indinavir caused a modest to marked increase in diltiazem levels, and a 1.9-fold increase in amlodipine levels. Based on this evidence, raised calcium-channel blocker levels are predicted when any calcium-channel blocker is given with a protease inhibitor, especially ritonavir. Caution is required. 

Ritonavir with Indinavir. Ritonavir/indinavir 100/800 mg twice daily given with diltiazem 120 mg daily for 7 days modestly increased the median AUC of diltiazem by 27% (not statistically significant) in 13 healthy subjects. However, two of the subjects had a fourfold increase in the AUC of diltiazem, and the desacetyl-diltiazem AUC increased by 102%. Diltiazem had no effect on the steady-state AUCs of the protease inhibitors. ... 

Protease inhibitors, particularly ritonavir (see Antivirals , (p.772)), are potent inhibitors of cytochrome P450 isoenzyme CYP3A4, by which all the calcium-channel blockers are extensively metabolised. It appears that some protease inhibitors can cause a clinically relevant increase in calcium-channel blocker levels. In addition, verapamil, diltiazem and nicardipine can also inhibit CYP3A4, and might therefore theoretically reduce the metabolism of the protease inhibitors. However, the effect might depend on which is the more potent inhibitor, since, in the studies above, diltiazem did not affect atazanavir, indinavir or ritonavir levels. 

Although information is limited, these pharmacokinetic interactions are predictable, and potentially serious. To date, clinically relevant increases in calcium-channel blocker levels or effects have been shown for nelfinavir with nifedipine or felodipine, indinavir/ritonavir with amlodipine, diltiazem or nifedipine, and atazanavir with diltiazem. Caution would be required with any of these combinations, anticipating the need to use lower doses of the calcium-channel blocker. The manufacturers specifically recommend that if diltiazem is given with atazanavir the initial dose of diltiazem should be reduced by 50% with subsequent dose titration and ECG monitoring. They also note that verapamil levels may be raised and therefore advise caution. Similarly, the manufaeturers of nifedipine say that blood pressure monitoring is required and a reduction in nifedipine dose may be neeessary if it is given with HIV-protease inhibitors. However, some UK manufacturers (e.g. felodipine, lercanidipine, nimodipine ) recommend avoiding the concurrent use of ritonavir and other protease inhibitors if possible. 

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