Ketoconazole alprazolam

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Greenblatt, D.J., Wright, C.E., von Moltke, L.L., Harmatz, J.S., Eh-renberg, B.L., Harrel, L.M., Corbett, K., Counihan, M., Tobias, S., and Shader, R.I. (1998) Ketoconazole inhibition of triazoloam and alprazolam clearance differential kinetic and dynamic consequences. Clin Pharmacol Ther 64 237-247. 

Figure 2 Mean ( SE) plasma concentrations of triazolam (left) or alprazolam (right) in a series of healthy individuals who participated in a clinical pharmacokinetic study. In one phase of the study, they ingested a single 0.25-mg oral dose of triazolam with ketoco-nazole, 200 mg twice daily, or with placebo to match ketoconazole (control). In the second phase of the study, they took 1.0 mg of alprazolam orally, either with the same dosage of ketoconazole or with placebo to match ketoconazole (control). Note that ketoconazole increases AUC and reduces clearance of both triazolam and alprazolam. For triazolam (a high-extraction compound), the effect is evident as reduced presystemic extraction, increased Cmax, and prolonged half-life. However, for alprazolam (a low-extraction compound), the effect of ketoconazole is evident only as a prolongation of half-life. Abbreviation AUC, the plasma concentration-time curve. Source Adapted, in part, from Ref. 74.

AUC) and increases in peak plasma concentration (Cmax) of triazolam (73,74) (Fig. 2). Cotreatment of ketoconazole with alprazolam, also a CYP3A substrate, produced a large increase in AUC for alprazolam (74). However, alprazolam is a low-extraction compound with bioavailability ordinarily in the range of 90% (75). As such, the reduction in alprazolam clearance caused by ketoconazole was evident mainly as prolonged elimination half-life but without a significant change in Cmax. 

Greenblatt DJ, Wright CE, von Moltke LL, et al. Ketoconazole inhibition of triazolam and alprazolam clearance differential kinetic and dynamic consequences. Clin Pharmacol Ther 1998 64 237-247. 

In a double-blind, crossover, pharmacokinetic and pharmacodynamic study of the interaction of ketoconazole with alprazolam and triazolam, two CYP3A4 substrate drugs with different kinetic profiles, impaired clearance by ketoconazole had more profound clinical consequences for triazolam than for alprazolam (39). 

FLUOXETINE, FLUVOXAMINE, PAROXETINE BZDs - ALPRAZOLAM, DIAZEPAM, MIDAZOLAM t in plasma concentrations of these BZDs. Likely t sedation and interference with psychomotor activity Alprazolam, diazepam and midazolam are subject to metabolism by CYP3A4. Fluvoxamine, fluoxetine and possibly paroxetine are inhibitors of CYP3A4 sertraline is a weak inhibitor. SSRIs are relatively weak compared with ketoconazole, which is possibly 100 times more potent as an inhibitor Warn patients about risks associated with activities that require alertness. Consider use of alternatives such as oxazepam, lorazepam and temazepam, which are metabolized by glucuronidation >- For signs and symptoms of CNS depression, see Clinical Features of Some Adverse Drug Interactions, Central nervous system depression... 

Thus, azole antifungal agents (such as ketoconazole and itraconazole), macrolide antibiotics, and protease inhibitors may also raise alprazolam plasma levels Inducers of CYP450 3A, such as carbamazepine, may increase clearance of alprazolam and lower alprazolam plasma levels and possibly reduce therapeutic effects... 

Benzodiazepines alprazolam, clonazepam, diazepam, midazolam, triazolam, zolpidem Calcium channel blockers diltiazem, nifedipine, nimodipine, verapamil Steroids androgens, estrogens, cortisol Others erythromycin, terfenadine, cyclosporine, dapsone, ketoconazole, lovastatin, lidocaine, alfentanil, amiodarone, astemizole, codeine, sildenafil... 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antip5Tine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bu-pivacaine, buspirone, butabarbital, caffeine, carbamazepine, cetirizine, chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, cyclizine, qyclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fu-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, mida-... 

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