Troleandomycin Triazolam

Warot D, Bergougnan L, Lamiable D, et al. Troleandomycin-triazolam interaction in healthy volunteers pharmacokinetic and psychometric evaluation. EurJ Clin Pharmacol 1987 32 389-393. 

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,... 

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

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a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn.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. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

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... 

Figure 3 Rates of formation of 4-OH-triazolam from triazolam (250 pM) by human liver microsomes in vitro. Each point is the mean ( SE) of four microsomal preparations. Reaction velocities when preparations were preincubated with the macrolide agents are expressed as a percentage of the control velocity with no inhibitor present (inhibitor = 0). Mean IC50 were TAO, 3.3 pM erythromycin, 27.3 pM clarithromycin, 25.2 pM azithromycin, >250 pM. Abbreviations IC50, 50% inhibitory concentrations TAO, troleandomycin. Source Adapted, in part, from Ref. 77.

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

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... 

The serum levels and effects of midazolam, triazolam and zopi-clone are markedly increased and prolonged by erythromycin. The same interaction has been seen with clarithromycin, josamy-cin, or troleandomycin but not azithromycin. Alprazolam would be expected to be similarly affected. Other benzodiazepines, and the related hypnotic zaleplon, appear not to interact with the macrolides to a clinically significant extent... 

The interactions of midazolam with erythromycin and triazolam with clarithromycin, erythromycin or troleandomycin appear to be established, and of clinical importance. The dosages of the midazolam and triazolam should be reduced 50 to 75% when these antibacterials are used if excessive effects (marked drowsiness, memory loss) are to be avoided. Remember too that the hypnotic effects are also prolonged so that patients should be warned about hangover effects the following morning if they intend to drive. Much less is known about the use of midazolam with clarithromycin but similar precautions may be necessary. The manufacturers of zaleplon say that patients should be advised that increased sedation is possible with erythromycin, although a dose adjustment is usually not required. ... 

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