Triazolam Clarithromycin

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

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,... 

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... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

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). 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

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 ... 

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.

Figure 5 Mean plasma TRZ concentrations following a single 0.125-mg oral dose of TRZ administered in Trials B, C, D, and E, as described in the text and in Fig. 4. Abbreviations TRZ, triazolam CLAR, clarithromycin ERY, erythromycin AZ, azithromycin PL, placebo. Source From Ref. 77.

Triazolam plasma concentrations were determined by gas chromatography with electron capture detection (73,95). The pharmacokinetic results demonstrated that mean clearance during Trials B and C were nearly identical (413 and 416 mL/min, respectively) that is, coadministration of azithromycin had no effect on the pharmacokinetics of triazolam (Fig. 5). However, triazolam clearance was significantly reduced to 146 mL/min by erythromycin (Trial D) and to 95 mL/min by clarithromycin (Trial E). Thus, the in vivo kinetic results are highly consistent with the in vitro data. 

A4/3A5 Midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, triazolam Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Rifampin, carbamazepine... 

In a randomized, double-bhnd, pharmacokinetic-pharmacodynamic study, 12 volunteers took placebo or triazolam 0.125 mg orally, together with placebo, azithromycin, erythromycin, or clarithromycin. The apparent oral clearance of triazolam was significantly reduced by erythromycin and clarithromycin. The peak plasma concentration was correspondingly increased, and the half-life was prolonged. The effects of triazolam on dynamic measures were nearly identical when triazolam was given with placebo or azithromycin, but benzodiazepine agonist effects were enhanced by erythromycin and clarithromycin (23). 

MIDAZOLAM, TRIAZOLAM, POSSIBLY ALPRAZOLAM MACROLIDES -ERYTHROMYCIN, CLARITHROMYCIN, TELITHROMYCIN t BZD levels Inhibition of CYP3A4-mediated metabolism 1 dose of BZD by 50% warn patients not to perform skilled tasks such as driving for at least 10 hours after the dose of BZD... 

In a randomized, double-blind, pharmacokinetic-pharmacodynamic study, 12 volunteers took placebo or triazolam 0.125 mg orally, together with placebo, azithromycin, erythromycin, or clarithromycin. The apparent oral... 

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... 

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