Ketoconazole Fluticasone

Ketoconazole A potent inhibitor of cytochrome P450 3A4 may increase plasma levels of budesonide and fluticasone during concomitant dosing. The clinical significance is unknown. Use caution. 

Use caution when coadministering high and prolonged doses of fluticasone with ketoconazole and other known cytochrome P450 inhibitors. 

Fluticasone, Nasal (Flonase) [Anti inflammotory/Corticos-teroid] Uses Seasonal all gic rhinitis Action Topical st oid Dose Adults Feds >12 y. 2 sprays/nostril/d Feds 4-11 y. 1-2 sprays/nostril/d Caution [C, M] Contra Primary Rx of status asthmaticus Disp Nasal spray meg SE HA, dysphonia, oral candidiasis Interactions t Effects ketoconazole EMS May... 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Ketoconazole reduces the metabolism and clearance of methylprednisolone. Ketoconazole may increase levels of the active metabolite of ciclesonide. Ketoconazole modestly increases the systemic effect of inhaled budesonide and possibly fluticasone, and markedly increases the AUC of oral budesonide. The situation with prednisone and prednisolone is uncertain studies have shown some moderate pharmacokinetic effects, but this does not appear to alter the action of either drug. 

Sixteen healthy subjects were given a single 500-microgram inhaled dose of fluticasone after taking ketoconazole 200 mg daily for 2 days. Plasma cortisol levels and urinary cortisol excretion were used as a measure of how much fluticasone was absorbed systemically, and it was found that ketoconazole had no effect on fluticasone absorption. However, the manufacturers of fluticasone cite a study in which the exposure to fluticasone was increased by 150% by ketoconazole, which resulted in reductions in plasma cortisol levels. ... 

Falcoz C, Lawlor C, Hefting KE Borgstein NG, Smeets FWM, Werner J, Jonkman JHG, House F. Effects of CYP3A4 inhibition by ketoconazole on systemic activity of inhaled fluticasone propionate and budesonide. EurRe irJ (1997) 10 (Suppl 25), 175S-176S. 

Kempsford R, Allen A, Bal J, Rubin D, Tombs L. The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects. Br J CUn Pharmacol Jime 2013 75(6) 1478-87. 

Fluticasone A double-blind, randomised, placebo-con-trolled, crossover study in healthy subjects evaluated the effects of ketoconazole on fluticasone pharmacokinetics [53fi. Ketoconazole increased fluticasone systemic exposure 36% indicating that fluticasone is a substrate of cytochrome P450 3A, but there was no increase in (i-agonist systemic pharmacodynamic effects. 

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