Ketoconazole Budesonide

CYP3A4 inhibitors If concomitant administration with ketoconazole or any other CYP3A4 inhibitor is indicated, closely monitor patients for increased signs and/or symptoms of hypercorticism. Consider reduction in budesonide dose. 

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. 

Budesonide, Oral (Entocort EC) [Anti-inflammatory> Corticosteroid] Uses Mild-mod Crohn Dz Action Steroid, anti-inflammatory Dose Adults. Initial, 9 mg PO qAM to 8 wk max maint 6 mg PO qAM taper by 3 mo avoid grapefruit juice Contra Active TB and fungal Infxn Caution [C, /-] DM, glaucoma, cataracts, HTN, CHF Disp Caps SE HA, cough, hoarseness, Candida Infxn, epistaxis Interactions T Effects W/ erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, grapefruit EMS Monitor ECG and BP for signs of electrolyte disturbances and hypovolemia OD Acute OD unlikely to cause a problem, chronic OD can reduce natural production of certain steroids symptomatic and supportive... 

In another study, ketoconazole was given orally as 200 mg od for 4 days, following a single oral dose of budesonide 3 mg either at the same time as ketoconazole or 12 hours before (483). Ketoconazole increased budesonide concentrations (Cmax and AUC) 6.8- to 7.6-fold when the two drugs were co-administered with a 12-hour separation, budesonide concentrations increased only 1.7-to 2.1-fold. 

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... 

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 subjeets were given a single 1-mg inhaled dose of budesonide after taking ketoeonazole 200 mg daily for 2 days. Plasma cortisol levels and urinary cortisol excretion were used as a measure of how much budesonide was absorbed systemically, and ketoconazole was found to cause a 37% decrease in the AUC0.24 of cortisol. ... 

Another study in 8 healthy subjects found that the AUC of a single 3-mg oral dose of budesonide was increased 6.5-fold when it was given with the last dose of ketoconazole 200 mg daily for 4 days. When budesonide was given 12 hours before the last dose of ketoconazole, the AUC was increased 3.8-fold. ... 

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. 

Seidegard J. Reduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics by separationof their time of administration. Clin Pharmacol Ther (2000) 68,13-17. 

The adverse effect profile of roflmnilast has been described previously. However, new data became available recently. A systematic review smnmarised the available data on adverse effects and drug reactions of roflmnilast. This systematic review was based on six clinical trials with a total population of 9102 COPD patients, with the study duration ranging between 24 and 52 weeks [89 ]. Roflmnilast is metabolised by CYP 3A4, CYP 2C19 and CYP 1A2. Inhibitors of these enzymes such as erythromycin or ketoconazole were shown to increase the activity and half-life of roflumilast. In contrast, drugs that induced these enzymes, like rifampicin, had the opposite effect, reducing the activity and half-life of roflumilast. Roflumilast did not significantly interact with montelukast, budesonide, or antacids. 

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