Midazolam Fluoxetine

Acenocoumarol, amiodarone, celecoxib, coumadin, dexamethasone, diclofenac, etoposide, fluconazole, fluoxetine, fluvas-tatin, fluvoxamine, ghmepiride, ghpizide, glyburide, ibuprofen, irbesartan, isoniazid, losartan, midazolam, phenylbutazone, phenytoin, rifampin, teniposide, tenoxicam, thiotepa, tolbutamide, torsemide, vitamin D, warfarin... 

Codeine, dextromethorphan, haloperidol, thioridazine, perphenazine, nortriptyline, desipramine, fluoxetine, norfluoxetine, TCAs (hydroxylation), beta-blockers such as timolol and metoprolol, type 1C antiarrhythmics encainide, flecainide TCAs (desmethylation), triazolam, alprazolam, midazolam, carbamazepine, terfenadine, quinidine, lidocaine, erythromycin, cyclosporin... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

For most child psychiatrists, the drug interactions most frequently encountered are interactions with other psychotropics. Fluoxetine inhibits the CYP3A isozymes and thus increase the plasma concentration of the tria-zolobenzodiazepines (alprazolam, midazolam, and triazolam), causing increased psychomotor effects (Shader and Greenblatt, 1995). To avoid unwanted psychomotor effects, the dosage of alprazolam should be decreased when it is coadministered with fluoxetine (Chouinard et ah, 1999). Nefazadone has also been shown to increase the pharmacodynamic effects of triazolam and, to a lesser extent, alprazolam (Chouinard et ah, 1999). 

Like fluoxetine, erythromycin and other macrolides inhibit the CYP-3A isoenzyme and increase the levels and effects of the triazolobenzodiazepines (Shader and Greenblatt, 1995 Chouinard et ah, 1999). Midazolam should be avoided or the dosage dropped by 50% in patients receiving erythromycin (Olkkola et ah, 1993). Ketoconazole and itraconazole may also interact with triazolam and midazolam, and combinations of these drugs should be avoided (Varhe et ah, 1994 Chouinard et ah, 1999). 

P450 IIIA3/4 T in women Inhibited by OCs Demethylation of TCAs, alprazolam, midazolam, triazolam, sertraline Fluoxetine, sertraline... 

BZD hypnotics such as midazolam and triazolam are primarily metabolized via the P450 3A3/4 microenzyme system. Other BZDs often used as hypnotics, such as diazepam, can also be metabolized by CYP 33/4 and CYP 2C19. Any drugs that act as inhibitors or inducers of these isoenzymes could increase or decrease BZD levels, respectively (350). Thus, ketoconazole, macrolide antibiotics (e.g., erythromycin), SSRIs (e.g., fluoxetine-norfluoxetine and fluvoxamine), and other antidepressants (especially nefazodone) may decrease clearance and increase BZD levels to potentially toxic ranges. Conversely, rifampacin, CBZ, and dexamethasone may increase clearance and decrease BZD levels to potentially subtherapeutic ranges. 

Lam, Y.W., Alfaro, C.L., Ereshefsky, L., and Miller, M., Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone, J. Clin. Pharmacol, 43(11), 1274-1282, 2003. 

A 43 year old man was premedicated for endoscopy with intravenous midazolam 2 mg and pethidine 50 mg). He immediately became agitated and restless. His blood pressure rose to 180/100 mmHg, he sweated, had widely dilated pupils, and had diarrhea. Over the next 90 minutes his condition remitted without specific treatment. He then reported that he had been taking fluoxetine (20 mg every other day), which he had stopped taken about 2 weeks before. 

In an in vitro study of midazolam biotransformation using human liver microsomes, midazolam metabolism was competitively inhibited by the antifungal azoles keto-conazole, itraconazole, and fluconazole, and the antidepressant fluoxetine and its metabolite norfluoxetine (55). The degree of inhibition was consistent with the inhibition reported in pharmacokinetic studies, and suggests that in vitro assay is useful for predicting significant interactions. 

Pharmacokinetic and pharmacodynamic interactions of midazolam with fluoxetine, fluvoxamine, nefazodone, and ketoconazole have been investigated in 40 healthy subjects (64). The mean AUC of midazolam was increased 772% by ketoconazole and 444% by nefazodone. However, fluoxetine and fluvoxamine had no significant effects. Nefazodone and ketoconazole caused significant increases in midazolam-related cognitive impairment, reflecting changed midazolam clearance. 

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... 

Clinically important, potentially hazardous interactions with alprazolam, aprepitant, astemizole, atorvastatin, benzodiazepines, carbamazepine, chlordiazepoxide, cilostazol, clonazepam, clorazepate, colchicine, conivaptan, cyclosporine, dabigatran, dasatinib, diazepam, digoxin, dihydroergotamine, disopyramide, ergot alkaloids, fesoterodine, fluoxetine, flurazepam, fluvastatin, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lorazepam, lovastatin, methylprednisolone, methysergide, midazolam, nilotinib, oxazepam, paroxetine, pimozide, pravastatin, prednisone, quazepam, repaglinide, rimonabant, rivaroxaban, sertraline, silodosin, simvastatin, solifenacin, temazepam, temsirolimus, tolvaptan, trabectedin, triazolam, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, bedomethasone, buprenorphine, calcium, chloramphenicol, cimetidine, dobazam, clorazepate, cyclosporine, cyproterone, darunavir, dasatinib, delavirdine, dexamethasone, diazoxide, disulfiram, dopamine, fesoterodine, fluconazole, flunisolide, fluoxetine, fosamprenavir, ginkgo biloba, hydrocortisone, imatinib, indinavir, influenza vaccines, isoniazid, isradipine, itraconazole, lacosamide, lapatinib, lopinavir, meperidine, methylprednisolone, midazolam, mivacurium, nelfinavir, nilotinib, nilutamide, phenylbutazone, piracetam, posaconazole, prednisolone, prednisone, primrose, ritonavir, rivaroxaban, sage, saquinavir, solifenacin, St John s wort, sucralfate, telithromycin, temsirolimus, teniposide, ticlopidine, tizanidine, tolvaptan, triamcinolone, uracil/tegafur, vigabatrin... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, 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, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

Also analyzed acebutolol, acetaminophen, alprazolam, amphetamine, atenolol, betaxolol, brotizolam, caffeine, camazepam, captopril, chloroquine, clobazam, clomipramine, cloth-iapine, clotiazepam, cloxazolam, cocaine, codeine, diclofenac, dihydralazine, dihydrocodeine, dihydroergotamine, diphenhydramine, domperidone, doxepin, droperidol, ergota-mine, ethyl loflazepate, fenethylline, fluoxetine, flupentixol, flurazepam, furosemide, gliclazide, hydrochlorothiazide, hydroxyzine, ibuprofen, imipramine, ketazolam, loprazo-1am, lorazepam, lormetazepam, maprotUine, medazepam, mepyramine, methadone, methaqualone, methyldopa, methylphenidate, metoclopramide, metoprolol, mexiletine, mianserin, midazolam, minoxidil, morphine, nadolol, nitrazepam, oxprenolol, papaverine, pentazocine, phenprocoumon, phenylbutazone, pipamperone, piritramide, practolol, pra-zepam, prazosin, promazine, promethazine, propoxyphene, propranolol, prothipendyl, quinine, sotalol, sulpride, thioridazine, trazodone, triazolam, trimipramine, tripelennamine, lyramine, verapeunil, yohimbine... 

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