Ciclesonide

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Nave R, Fisher R, Zech K (2006) In vitro metabolism of ciclesonide in human lung and liver precision-cut tissue slices. Biopharm Drug Dispos 27 197-207. 

Ciclesonide anti-infalammatory block late reaction to thinning and bruising... 

Aerosol treatment is the most effective way to avoid the systemic adverse effects of corticosteroid therapy. The introduction of corticosteroids such as beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone... 

The effect of inhaled ciclesonide on adrenal function has been analysed in 164 asthmatic adults in a double-blind, randomized, placebo-controlled study (40). The patients used ciclesonide 320 micrograms once daily, ciclesonide 320 micrograms twice daily, or fluticasone propionate 440 micrograms twice daily for 12 weeks. Adrenal function was significantly suppressed by fluticasone propionate but not by ciclesonide. Oral candidiasis was reported in 2.4% of patients on ciclesonide versus 22% of patients on fluticasone propionate. Even high daily doses of ciclesonide up to 1280 micrograms did not suppress adrenal function, as measured by 24-hour urinary cortisol excretion (41). This is in accordance with other studies in asthmatic subjects, in which serum or 24-hour urinary cortisol concentrations were unchanged by ciclesonide (42-48). 

In general, ciclesonide in daily doses of up to 640 micrograms can be considered to be safe with respect to adrenal function. Its long-term safety profile is similarly advantageous, and administration in daily doses up to 1280 micrograms over 52 weeks was not associated with systemic or local adverse effects in patients with persistent asthma (50). 

Short-term lower-leg growth rate and adrenal function was assessed in 24 children aged 6-12 years using increasing doses of ciclesonide (40, 80, and 160 micrograms) in a randomized, double-blind, placebo-controlled, crossover study (75). Ciclesonide had no effect on lower-leg growth rate or adrenal function. 

Lipworth BJ, Kaliner MA, LaForce CF, Baker JW, Kaiser HB, Amin D, Kundu S, Williams JE, Engelstaetter R, Banerji DD. Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma. Ann Allergy Asthma Immunol 2005 94 465-72. 

Szefler SJ, Rohatagi S, Williams JE, Lloyd M, Kundu S, Banerji D. Ciclesonide, a novel inhaled steroid, does not affect hypothalamic-pituitary-adrenal axis function in patients with moderate-to-severe persistent asthma. Chest 2005 128(3) 1104-14. 

Derom E, Van DV, V, Marissens S, Engelstatter R, Vincken W, Pauwels R. Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5 monophosphate in asthmatic patients. Pulm Pharmacol Ther 2005 18 328-36. 

Langdon CG, Adler M, Mehra S, Alexander M, Drollmann A. Once-daily ciclesonide 80 or 320 microg for 12 weeks is safe and effective in patients with persistent asthma. Respir Med 2005 99 1275-85. 

Pearlman DS, Berger WE, Kerwin E, LaForce C, Kundu S, Banerji D. Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma. J Allergy Clin Immunol 2005 116 1206-12. 

Postma DS, Sevette C, Martinat Y, Schlosser N, Aumann J, Kafe H. Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Eur Respir J 2001 17 1083-8. 

Weinbrenner A, Huneke D, Zschiesche M, Engel G, Timmer W, Steinijans VW, Bethke T, Wurst W, Drollmann A, Kaatz HJ, Siegmund W. Circadian rhythm of serum cortisol after repeated inhalation of the new topical steroid ciclesonide. J Clin Endocrinol Metab 2002 87 2160-3. 

Lee DK, Fardon TC, Bates CE, Haggart K, McFarlane LC, Lipworth BJ. Airway and systemic effects of hydrofluor-oalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma. Chest 2005 127 851-60. 

Rohatagi S, Krishnaswami S, Pfister M, Sahasranaman S. Model-based covariate pharmacokinetic analysis and lack of cortisol suppression by the new inhaled corticosteroid ciclesonide using a novel cortisol release model. Am J Ther... 

Chapman KR, Boulet LP, D Urzo AD. Long-term administration of ciclesonide is safe and well tolerated in patients with persistent asthma. 4th Triennial World Asthma Meeting (WAM). February 16-19, Bangkok, Thailand, 2004 61. 

Cidesonide is an agent that is inactive until it reaches its target site - the lung - where it is converted to its active metabolite des-isobutyryl-ciclesonide, catalyzed by esterases in the lung, whereas further metabolism of des-isobutyryl-ddesonide to inactive metabolites occurs in the liver and is catalyzed by cytochrome P450 enzymes, especially by CYP 3A4. 

Arofylline, 202 Cariporide, 57 Dronaderone, 140 Regadenoson, 197 Selodenoson, 196 Tecadenoson, 195 Antiasthmatic Atreluton, 90 Ciclesonide, 36 Cilomilast, 30 Roflumilast, 44 Antibacterial Amustaline, 218 Ceftobiprole, 213 Eitapenem, 214 Garfenoxacin, 176 Gatifloxacin, 174 Gemifloxacin, 210 Iclaprim, 125... 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with benzodiazepines, carbamazepine, chlordiazepoxide, ciclesonide, clonazepam, clorazepate, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, eszopiclone, eucalyptus, fentanyl, fesoterodine, flurazepam, ivabradine, lapatinib, lorazepam, methysergide, midazolam, oral contraceptives, oxazepam, phenytoin, pimozide, quazepam, rifampin, sildenafil, solifenacin, St John s wort, temazepam, temsirolimus, tolvaptan... 

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... 

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