Triazolam Cimetidine

Parker WA, MacLachlan RA. Prolonged hypnotic response to triazolam-cimetidine combination in an elderly patient. Drug Intell Clin Pharm (1984) 18,980-1. 

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... 

Triazolam potentiates the CNS depressant effects of phenothiazines, narcotics, antihistamines, MAOIs, barbiturates, alcohol, general anesthetics, and antidepressants. Use with cimetidine and disulfiram may increase triazolam s plasma concentration. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Drugs metabolized by CYP that interact with cimetidine include, but are not limited to, the following lidocaine, quinidine, midazolam, triazolam, nifedipine, verapamil, and fentanyl (4). In each instance, inhibition of CYP by cimetidine results in reduced metabolic clearance and increases in serum concentrations of the other drug, which can lead to the expected toxicity and adverse experiences characteristic of the other drug. 

Pourbaix S, Desager JP, Hulhoven R, Smith RB, Harvengt C. Pharmacokinetic consequences of long term coadministration of cimetidine and triazolo-benzodiazepines, alprazolam and triazolam, in healthy subjects. Int J Clin Pharmacol Ther Toxicol 1985 23(8) 447-51. 

Abernethy DR, Greenblatt DJ, DivoU M, Moschitto LJ, Harmatz JS, Shader RI. Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology (Berl) 1983 80(3) 275-8. 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

Imidazole, 1-methylimidazole, L-histidine, ethylenediamine, caffeine and teophylline were purchased from Kanto Chemicals. Cimetidine, famotidine, omeprazole, thioperamide and dansyl-L-phenylalanine (DNS-Phe) were from Sigma. Histamine (Nacalai Tesque), 3-methylhistamine dihydrochloride (Calbiochem), bis(2,4,6-trichlorophenyl)oxalate (TCPO Tokyo Kasei) and hydrogen peroxide (31% H2O2 Mitsubishi Gas Chemicals) were used as received. Triazolam, estazolam, midazolam and alprazolam were generously supplied from pharmaceutical companies. Special... 

Concomitant use with cimetidine and possibly disulfiram causes diminished hepatic metabohsm of triazolam, which increases its plasma concentration. 

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... 

The combined serum level of diazepam and its active metabolite, des-methyldiazepam, was found to be increased by 75% in 10 patients who took cimetidine 300 mg four times daily for 2 weeks, but reaction times and other motor and intellectual tests remained unaffected. Other reports describe a rise in the plasma levels and/or AUC of diazepam (associated with increased sedation in one report ) due to cimetidine, and generalised incoordination has also been described in one individual. Cimetidine also raises the serum levels of adinazolam, alprazolam, chlordiazepoxide, clobazam, clorazepate, flu-razepam, nitrazepam, and triazolam, > > > and reduces the clearance of bromazepam. ... 

Liver cirrhosis increases the effects of cimetidine on the loss of chlo-rdiazepoxide. Confusion has been reported in a 50-year-old man taking clorazepate when he was given cimetidine, and increased sedation has been seen in some patients taking adinazolam and cimetidine. Prolonged hypnosis in an elderly woman and CNS toxicity (including lethargy and hallueinations) in a 49-year-old woman have been attributed to an interaction between triazolam and cimetidine but this remains unconfirmed. 

Cimetidine inhibits the liver enzymes concerned with the metabolism of diazepam, alprazolam, chlordiazepoxide, clomethiazole, clorazepate, flu-razepam, nitrazepam, triazolam, and zaleplon. As a result their clearance from the body is reduced and their serum levels rise. 

Ranitidine, famotidine and nizatidine appear not to inhibit liver microsomal enzymes. There is some evidence that ranitidine increases the absorption of triazolam, and possibly other benzodiazepines, due to changes in gastric pH, ° although it has been suggested that this effect is negligi-ble. ° Cimetidine has been said to similarly affect the absorption of diazepam and lorazepam. ... 

Friedman H, Greenblatt DJ, Burstein ES, Scavone JM, Harmatz JS, Shader RI. Triazolam kinetics interaction with cimetidine, propranolol, and the combination. J CUn Pharmacol... 

Cox SR, Kroboth PD, Anderson PH, Smith RB. Mechanism for the interaction between triazolam and cimetidine. Biopharm Drug Dispos (198Q 7, 567-75. 

Britton ML, Waller ES. Central nervoussystem toxicity associated with concurrent use of triazolam and cimetidine. Drug Intell Clin Pharm (1985) 19,666-8. 

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