Methylprednisolone interactions

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,... 

A retrospective analysis of 3995 patients treated with azithromycin did not show any pharmacokinetic interactions in patients who were also taking various other drugs, including methylprednisolone (1,45). 

Co-administration of diltiazem with methylprednisolone increased plasma concentrations of methylprednisolone and its adrenal suppressant effects in nine healthy volunteers (29). Care should be taken when these two drugs are co-administered for a long period, even if the clinical relevance of this pharmacokinetic interaction still needs to be evaluated. 

The interaction of itraconazole with oral methylprednisolone has been examined in a randomized, double-blind, crossover study in 10 healthy volunteers taking either oral itraconazole 200 mg/day or placebo for 4 days (95). On day 4 each subject took methylprednisolone 16 mg. Itraconazole increased the total AUC of methylprednisolone 3.9-fold compared with placebo, the peak plasma methylprednisolone concentration 1.9-fold, and the half-Ufe 2.4-fold. This effect was probably through inhibition of CYP3A4. 

The minor interaction of itraconazole with oral prednisolone is probably of limited clinical significance. The susceptibility of prednisolone to interact with CYP3A4 inhibitors is considerably smaller than that of methylprednisolone, and itraconazole and probably also other inhibitors of CYP3A4 can be used concomitantly with prednisolone without marked interaction. 

The effect of ketoconazole on steroid metabolism is reflected in other interactions. Ketoconazole increases the total amount of methylprednisolone in the body (SED-12, 678) (47). 

Some macrolides have a dose- and time-related effect on methylprednisolone elimination, resulting in a prolonged half-life and reduced clearance (157). These changes were considered advantageous (steroid sparing) in patients with asthma (158,159). However, a retrospective analysis of 3995 patients treated with azithromycin did not show any pharmacokinetic interaction in patients who were also taking methylprednisolone (127,128). 

The kinetic behavior of theophylUne given concomitantly with methylprednisolone and auranofin to six women suggested a possible interaction of theophyUine with auranofin, although a role of the corticosteroid could not be ruled out. The observed concentrations of theophyUine were lower than expected, suggesting the need to measure serum theophyUine concentrations in patients who also take steroids and gold salts (54). 

Clinically important, potentially hazardous interactions with adenosine, arformoterol, BCG vaccine, capsicum, carbimazole, cimetidine, ciprofloxacin, clorazepate, cocoa, erythromycin, eucalyptus, fluvoxamine, halothane, influenza vaccines, mebendazole, methylprednisolone, nilutamide, oral contraceptives, prednisolone, prednisone, rasagiline, raspberry leaf, roxithromycin, St John s wort, torasemide, torsemide... 

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 acenocoumarol, anagrelide, anticoagulants, bismuth, boswellia, calcium hydroxylapatite, capsicum, cholestyramine, desvenlafaxine, devil s claw, dexamethasone, dexibuprofen, dicumarol, etodolac, evening primrose, flunisolide, ginkgo biloba, ginseng, heparin, ibuprofen, indomethacin, ketoprofen, ketorolac, lumiracoxib, methotrexate, methylprednisolone, nilutamide, NSAIDs, phellodendron, prednisone, resveratrol, reteplase, rivaroxaban, sermorelin, sulfites, tirofiban, triamcinolone, urokinase, valdecoxib, valproic acid, verapamil, 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 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 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 corticosteroids, cyclosporine, hemophilus B vaccine, methylprednisolone, mycophenolate, prednisolone... 

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... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

These effects were explained by the authors by the following findings 1) atropine reversibly inhibited NTE protecting its inhibition with DFP [10,113] b) TMB-4 caused partial reactivation of DFP-inhibited NTE decreasing the level of inhibition and aging on NTE with eventual direct interaction with the inhibitor c) given in repeated doses methylprednisolone was antiinflammatory and could influence the maintenance of the functions of neurons. 

After absorption, aprepitant is bound extensively to plasma proteins (>95%) it is extensively metabolized, primarily by hepatic CYP3A4, and is excreted in the stool its t is 9—13 hours. Aprepitant has the potential to interact with other substrates of CYP3A4, requiring adjustment of other drugs, including dexamethasone, methylprednisolone (whose dose may need to be reduced by 50%), and warfarin. Aprepitant is contraindicated in patients on cisapride (see above) or pimozide, in whom life-threatening ventricular tachyarrthmias has been reported. 

Since erythromycin complexes and inactivates drug oxidizing systems such as cytochrome P-450, it has the potential to alter the metabolism of other drugs. The metabolism and excretion of theophylline, warfarin, carbamaz-epine, and methylprednisolone are inhibited by erythromycin [283-286]. As a potent antibiotic, it can also affect metabolism by gut micro-organisms of drugs such as digoxin. At least some of the newer derivatives may cause fewer drug interactions and thus may be better tolerated if co-administered with medications for other illnesses [287-289]. 

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