Interaction between
Budesonide
and
Ceritinib
Major
Metabolism
Basic Information
| ID | DDInter246 and DDInter340 |
| Interaction | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the systemic bioavailability of budesonide, which undergoes extensive first-pass and systemic metabolism via intestinal and hepatic CYP450 3A4. |
| Management | Concomitant use of budesonide with potent CYP450 3A4 inhibitors should generally be avoided. Alternatives to budesonide should be considered whenever possible, particularly for long-term use. If an orally inhaled corticosteroid is necessary, a less potent, less lipophilic, and/or shorter-acting agent such as beclomethasone or flunisolide may be appropriate. If no alternatives exist and concomitant use is required, the dosing times between budesonide and the CYP450 3A4 inhibitor should be separated by as much as possible. In addition, the lowest effective dosage of budesonide should be prescribed, and further adjustments made as necessary according to therapeutic response and tolerance. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if budesonide is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma). |
| References | [1] Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT "Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole." Clin Pharmacol Ther 72 (2002): 362-369 [2] Edsbacker S, Andersson T "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet 43 (2004): 803-21 [3] De Wachter E, Vanbesien J, De Schutter I, Malfroot A, De Schepper J "Rapidly developing Cushing syndrome in a 4-year-old patient during combined treatment with itraconazole and inhaled budesonide." Eur J Pediatr (2003): [4] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [5] Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN "Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole." Ann Pharmacother 38 (2004): 46-9 [6] Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S "Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide." Eur Respir J 20 (2002): 127-33 [7] "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation, Kenilworth, NJ. [8] Molimard M, Girodet PO, Pollet C, et al. "Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical presentation." Drug Saf 31 (2008): 769-74 [9] Kedem E, Shahar E, Hassoun G, Pollack S "Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient." J Asthma 47 (2010): 830-1 [10] "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals, Cambridge, MA. [11] De Wachter E, Malfroot A, De Schutter I, Vanbesien J, De Schepper J "Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to drug inhibition of cytochrome P450." J Calif Dent Assoc 2 (2003): 72-5 [12] Jonsson G, Astrom A, Andersson P "Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver." Drug Metab Dispos 23 (1995): 137-42 [13] Cerner Multum, Inc. "Australian Product Information." O 0 [14] Daveluy A, Raignoux C, Miremont-Salame G, et al. "Drug interactions between inhaled corticosteroids and enzymatic inhibitors." Eur J Clin Pharmacol (2009): [15] "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc, Mississauga, ON. [16] Main KM, Skov M, Sillesen IB, et al. "Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient." Acta Paediatr 91 (2002): 1008-11 [17] "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc, Mississauga, ON. [18] Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67 [19] "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals, New York, NY. |
| Alternative for Budesonide |
R03A
D07A |
| Alternative for Ceritinib |
L01E
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.