Troleandomycin Methylprednisolone

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,... 

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 acetylcysteine, adenosine, aprepitant, aripiprazole, buprenorphine, caffeine, charcoal, clarithromycin, clobazam, dorazepate, clozapine, darunavir, dasatinib, delavirdine, dexamethasone, diltiazem, doxacurium, erythromycin, felodipine, fesoterodine, fosamprenavir, imatinib, influenza vaccines, lacosamide, lapatinib, levetiracetam, lopinavir, methylprednisolone, midazolam, nelfinavir, nilotinib, piracetam, prednisolone, propoxyphene, ritonavir, rivaroxaban, rufinamide, solifenacin, St John s wort, telithromycin, temsirolimus, terbinafine, tolvaptan, troleandomycin, verapamil, voriconazole... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

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... 

Clinically important, potentially hazardous interactions with aminophylline, anticonvulsants, aprepitant, bedomethasone, bosentan, budesonide, cigarette smoking, danazol, efavirenz, exenatide, flucloxacillin, flunisolide, fluticasone, hydrocortisone, insulin detemir, lamotrigine, licorice, lymecycline, methylprednisolone, modafinil, nelfinavir, prednisolone, prednisone, rifabutin, rifampin, ritonavir, saw palmetto, selegiline, St John s wort, triamcinolone, troleandomycin, tuberculostatics, ursodeoxycholic acid, zolmitriptan... 

Ebling, W.F. Szefler, S.J. Jusko, W.J. Analysis of cortisol, methylprednisolone, and methylprednisolone hemisuccinate. Absence of effects of troleandomycin on ester hydrolysis. J.Chromatogr., 1984, 305, 271-280... 

Troleandomycin and, to a lesser extent, clarithromycin and erythromycin can reduce the clearance of methylprednisolone, thereby increasing both its therapeutic and adverse effects. A patient receiving long-term clarithromycin developed Cushing s syndrome after starting treatment with inhaled budesonide. There appears to be no pharmacokinetic interaction between erythromycin and inhaled ciclesonide. Similarly, prednisolone appears not to be affected by macrolides, except possibly in those also taking enzyme-inducers such as phenobarbital. Isolated case reports describe the development of acute mania and psychosis in two patients, apparently due to an interaction between prednisone and clarithromycin. 

Troleandomydn. A pharmacokinetic study in 4 children and 6 adult corticosteroid-dependent asthmatics found that troleandomycin 14 mg/kg daily for one week increased the half-life of methylprednisolone by 88%, from 2.46 to 4.63 hours, and reduced the total body clearance by 64%. All 10 had Cushingoid symptoms (cushingoid facies and weight gain), which resolved when the methylprednisolone dosage was reduced, without any loss in the control of the asthma. Another study found that the dose of methylprednisolone could be reduced by 50% in the presence of troleandomycin, without loss of disease control. Other studies have found similar effects. However, a randomised, placebo-controlled 2-year study found that although troleandomycin modestly reduced the lequiied dose... 

What is known suggests that clarithromycin, erythromycin and troleandomycin can inhibit the metabolism of methylprednisolone. The volume of distribution is also decreased. Clarithromycin may inhibit the metabolism of budesonide. ... 

Information about the clarithromycin or erythromycin interactions with methylprednisolone is much more limited than with the interaction between troleandomycin and methylprednisolone, but they all appear to be established and of clinical importance. The effect should be taken into account during concurrent use and appropriate dosage reductions made to avoid the development of corticosteroid adverse effects. The authors of one study suggest that this reduction should be empirical, based primarily on clinical symptomatology. Another group found that a 68% reduction in methylprednisolone dosage was possible within 2 weeks. Troleandomycin appears to have a greater effect than erythromycin or clarithromycin. 

Ketoconazole can lead to reduced clearance of CS and a mild increase in levels (62,66,67). In addition, patients with significant liver or renal failure, age older than 65 years (68), or women receiving exogenous estrogen have increased unbound concentrations of prednisolone (69). Conversely, hyperthyroid patients have lower levels (70). There is one case report of an increased prothrombin time occurring in a patient on a stable dose of coumadin who subsequently received prednisone (71). This interaction seems rare and may be overshadowed by other drugs and events in the patient. Troleandomycin, a macrolide, has been shown to reduce clearance of methylprednisolone, but not prednisone (72). 

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