Methylprednisolone Itraconazole

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,... 

Itraconazole 200 mg/day markedly increased plasma methylprednisolone concentrations and reduced morning plasma cortisol concentrations by over 80% in 10 healthy volunteers (479). The Cmax, AUC, and half-life of... 

Itraconazole 200 mg/day orally for 4 days markedly reduced the clearance and increased the half-life of intravenous methylprednisolone from 2.1 to 4.8 hours in a double-blind, randomized, two-phase, crossover study in nine healthy volunteers (SEDA-23,430 480). The volume of distribution was not affected. The mean morning plasma cortisol concentration during the itraconazole phase, measured 24 hours after methylprednisolone, was only 9% of that during the placebo phase (11 versus 117 ng/ml). 

The authors of these two reports recommended that care be taken when methylprednisolone is prescribed in combination with itraconazole or other potent inhibitors of CYP3A4. 

Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther 1998 64(4) 363-8. 

Varis T, Kivisto KT, Backman JT, Neuvonen PJ. Itraconazole decreases the clearance and enhances the effects of intravenously administered methylprednisolone in healthy volunteers. Pharmacol Toxicol 1999 85(l) 29-32. 

A 34-year-old renal transplant recipient taking a stable regimen of tacrolimus and methylprednisolone was given itraconazole 100 mg bd for a yeast infection of the urinary tract (115). Concomitant therapy with itraconazole led to a marked increase in tacrolimus trough concentrations on the second day of therapy (from 13 to 21 ng/ml) and an increase in serum creatinine concentrations, necessitating dosage reduction of tacrolimus by 50%. 

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 effects of oral itraconazole (400 mg on the first day, then 200 mg/day for 3 days) on the pharmacokinetics of a single oral dose of methylprednisolone 48 mg have... 

The effects of oral itraconazole (400 mg on the first day then 200 mg/day for 3 days) on the pharmacokinetics of a single oral dose of prednisolone 60 mg or methylprednisolone 48 mg have been studied in 14 healthy men in a two-period, crossover study (97). Plasma cortisol concentrations were determined as a pharmacodjmamic index. The disposition of prednisolone was unchanged. 

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. 

Lebrun-Vignes B, Archer VC, Diquet B, Levron JC, Chosidow O, Puech AJ, Warot D. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br J Clin Pharmacol 2001 51(5) 443-50. 

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 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 amprenavir, aprepitant, bedomethasone, buprenorphine, calcium, chloramphenicol, cimetidine, dobazam, clorazepate, cyclosporine, cyproterone, darunavir, dasatinib, delavirdine, dexamethasone, diazoxide, disulfiram, dopamine, fesoterodine, fluconazole, flunisolide, fluoxetine, fosamprenavir, ginkgo biloba, hydrocortisone, imatinib, indinavir, influenza vaccines, isoniazid, isradipine, itraconazole, lacosamide, lapatinib, lopinavir, meperidine, methylprednisolone, midazolam, mivacurium, nelfinavir, nilotinib, nilutamide, phenylbutazone, piracetam, posaconazole, prednisolone, prednisone, primrose, ritonavir, rivaroxaban, sage, saquinavir, solifenacin, St John s wort, sucralfate, telithromycin, temsirolimus, teniposide, ticlopidine, tizanidine, tolvaptan, triamcinolone, uracil/tegafur, vigabatrin... 

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... 

Clarithromycin, danazol, diltiazem, erythromycin, fluconazole, fluvoxamine, grapefruit juice, itraconazole, ketoconazole, methylprednisolone, methyltestosterone, nicardipine, norethisterone, protease inhibitors, verapamil... 

A study in 14 healthy subjects found that itraconazole 400 mg for one day and then 200 mg daily for the next 3 days, increased the AUC of a single 48-mg dose of methylprednisolone by more than 2.5-fold." Other studies in healthy subjeets have found that itraeonazole decreases the clearance, and inereases the elimination half-life and AUC of both oral and intravenous methylprednisolone. Enhaneed adrenal suppression also occurred. ... 

Respiratoiy A 53-year-old man with chronic pulmonary aspergillosis developed near-fatal diffuse alveolar hemorrhage after receiving intravenous itraconazole a lymphocyte stimulation test was positive he did not respond to methylprednisolone but responded dramatically to hemoperfusion using a poly-m) in B-immobiUzed fiber column P6 ]. 

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