pulmicort and Cushing-Syndrome

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Controlled Clinical Trials as Topic; Cushing Syndrome; Delayed-Action Preparations; Double-Blind Method; Fluticasone; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Remission Induction

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents; Azoles; Budesonide; Cushing Syndrome; Drug Interactions; Female; Gastrointestinal Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Iatrogenic Disease; Leukemia, Myeloid, Acute; Male; Middle Aged; Transplantation, Homologous

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to

Topics: Adrenal Cortex Hormones; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Budesonide; Cushing Syndrome; Dyspnea; Female; Humans; Iatrogenic Disease; Itraconazole

Oral budesonide is commonly used for the management of Crohn's disease given its high affinity for glucocorticoid receptors and low systemic activity due to extensive first-pass metabolism through hepatic cytochrome P450 (CYP) 3A4. Voriconazole, a second-generation triazole antifungal agent, is both a substrate and potent inhibitor of CYP isoenzymes, specifically CYP2C19, CYP2C9, and CYP3A4; thus, the potential for drug-drug interactions with voriconazole is high. To our knowledge, drug-drug interactions between voriconazole and corticosteroids have not been specifically reported in the literature. We describe a 48-year-old woman who was receiving oral budesonide 9 mg/day for the management of Crohn's disease and was diagnosed with fluconazole-resistant Candida albicans esophagitis; oral voriconazole 200 mg every 12 hours for 3 weeks was prescribed for treatment. Because the patient experienced recurrent symptoms of dysphagia, a second 3-week course of voriconazole therapy was taken. Seven weeks after originally being prescribed voriconazole, she came to her primary care clinic with elevated blood pressure, lower extremity edema, and weight gain; she was prescribed a diuretic and evaluated for renal dysfunction. At a follow-up visit 6 weeks later with her specialty clinic, the patient's blood pressure was elevated, and her physical examination was notable for moon facies, posterior cervical fat pad prominence, and lower extremity pitting edema. Iatrogenic Cushing syndrome due to a drug-drug interaction between voriconazole and budesonide was suspected, and voriconazole was discontinued. Budesonide was continued as previously prescribed for her Crohn's disease. On reevaluation 2 months later, the patient's Cushingoid features had markedly regressed. To our knowledge, this is the first published case report of iatrogenic Cushing syndrome due to a probable interaction between voriconazole and oral budesonide. In patients presenting with Cushingoid features who have received these drugs concomitantly, clinicians should consider the potential drug interaction between these agents, and the risks and benefits of continued therapy must be considered.

Topics: Adrenal Cortex Hormones; Antifungal Agents; Budesonide; Cushing Syndrome; Drug Interactions; Female; Humans; Iatrogenic Disease; Middle Aged; Voriconazole

A 48-year-old woman with HIV infection developed Cushingoid features while she was taking ritonavir-boosted darunavir. Cushing's syndrome was confirmed due to the drug interaction between ritonavir and budesonide. Diagnosis of iatrogenic Cushing's syndrome in HIV-positive patients who are on ritonavir-boosted protease inhibitors (PIs) presents a clinical challenge due to similar clinical features of lipohypertrophy related to ritonavir-boosted PIs. Although this complication has been widely described with the use of inhaled fluticasone, the interaction with inhaled budesonide at therapeutic dose is not widely recognized.

Topics: Administration, Inhalation; Anti-HIV Agents; Budesonide; Cushing Syndrome; Drug Interactions; Female; HIV Infections; Humans; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System; Ritonavir

Topics: Aged; Atazanavir Sulfate; Budesonide; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; Humans; Male; Oligopeptides; Pyridines; Ritonavir

Topics: Adrenal Insufficiency; Bronchiolitis Obliterans; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cushing Syndrome; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Pulmonary Disease, Chronic Obstructive; Rhinitis, Allergic, Perennial; Ritonavir

Iatrogenic Cushing's syndrome (CS) is caused by exposure to glucocorticoids and may be promoted by interaction with additional drugs. It is well known in asthmatic human immunodeficiency virus (HIV)-infected patients treated with inhaled fluticasone with ritonavir-containing antiretroviral regimen (cART).. The authors present an asthmatic HIV-infected Ethiopian woman, treated with fluticasone/salmeterol, commencing cART with tenofovir, emtricitabine, and lopinavir/ritonavir. During 7 months she gained 9 kg and hyperpigmentation, mild edema, marked abdominal striae, and increase in blood pressure were noted. Plasma am and urine free cortisol levels confirmed CS diagnosis and fluticasone was discontinued. Complete resolution of CS occurred within 2 months. However, frequent asthma symptoms required resumption of inhaled corticosteroid (ICS) treatment, and budesonide/formeterol was prescribed. Soon reemergence of symptomatic CS was noted. Ritonavir dose was halved, but CS symptoms continued to develop. Budesonide was stopped and montelukast initiated. Resolution of cushingoid symptoms was observed within weeks.. Corticosteroids are metabolized by cytochrome P450 3A4 (CYP3A4). Fluticasone has the longest glucocorticoid receptor-binding half-life and is 300 times more lipophilic than budesonide. Inhaled fluticasone possesses a high suppression rate of hypothalamic-pituitary-adrenal axis. Ritonavir, a potent CYP3A4 inhibitor, may inhibit corticosteroid degradation and increase its accumulation. Inhaled budesonide is less likely to cause adrenal suppression. Diagnosing Cushing's syndrome presents a clinical challenge due to similarities with clinical manifestations and side effects related to cART. In patients treated with inhaled or intranasal corticosteroids together with cART there may be a higher incidence of iatrogenic CS. CS should be looked for, and management considered carefully.

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Female; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

Adrenal insufficiency (AI) is a potentially life-threatening condition. It is known that high doses of inhaled corticosteroids (ICS) can induce systemic adverse effects. Currently, there are no data on the prevalence of AI associated with the use of ICS. This study aimed to investigate the prevalence and clinical presentation of AI (associated or not associated with exogenous Cushing's syndrome) in patients who were prescribed ICS by French physicians during the period 2000-5.. All metropolitan French paediatricians, endocrinologists, pulmonologists and intensive care physicians (n = 11 783) were mailed questionnaires requesting information regarding cases of AI associated or not associated with exogenous Cushing's syndrome between 2000 and 2005. Data collected included patient demographics, oral corticosteroid or ICS used during the year preceding the diagnosis of AI, underlying condition(s), concomitant treatment(s), presenting clinical signs and symptoms, results of laboratory investigations and outcome. The French pharmacovigilance database was screened for spontaneous reports to determine the frequency of AI associated with the use of ICS, using the capture-recapture method.. Forty-six cases of AI were identified. Twenty-three cases presented with clinical symptoms of AI alone and 23 with exogenous Cushing's syndrome. ICS prescribed were fluticasone propionate (n = 24), budesonide (n = 12) and beclometasone dipropionate (n = 5). In 82% (n = 32) of cases for which data were available, ICS were prescribed at high doses. A potential drug interaction was found in 12 cases. Thirteen cases of AI were identified in the French pharmacovigilance database, one of which was common with the questionnaire survey. The capture-recapture method provided an estimation of 598 (95% CI 551, 648) cases of AI associated with the use of ICS for the 2000-5 period in France.. The results of this study confirm the occurrence of adrenal insufficiency in patients treated with ICS. Although the prevalence of ICS-induced AI reported in this study is low, the likelihood of under-diagnosis underlines the need to consider this risk in patients when prescribing these drugs.

Topics: Administration, Inhalation; Adolescent; Adrenal Insufficiency; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Androstadienes; Beclomethasone; Budesonide; Child; Child, Preschool; Cushing Syndrome; Data Collection; Databases, Factual; Drug Interactions; Female; Fluticasone; France; Glucocorticoids; Humans; Infant; Male; Middle Aged; Prevalence; Young Adult

To report a case of an interaction between inhaled corticosteroids and itraconazole causing iatrogenic Cushing's syndrome and provide a review of the relevant literature.. A 70-year-old white woman on long-term treatment with high-dose inhaled corticosteroids for asthma was diagnosed as having Scedosporium apiospermum infection of the skin and subcutaneous tissues. As a result, she was treated with itraconazole for 2 months. She subsequently developed Cushing's syndrome due to a probable cytochrome P450-mediated interaction between itraconazole and budesonide. She also had secondary adrenal insufficiency requiring prolonged treatment with replacement hydrocortisone.. Budesonide is a potent glucocorticoid that is metabolized in the liver by the CYP3A4 isoenzyme to inactive metabolites. Itraconazole is a potent cytochrome P450 inhibitor. It can inhibit the metabolism of oral or inhaled corticosteroids, producing cortisol excess leading to Cushing's syndrome and adrenal insufficiency. An assessment of causality indicated a possible adverse interaction between itraconazole and budesonide.. The combination of itraconazole and inhaled corticosteroids is increasingly being used to treat conditions such as allergic bronchopulmonary aspergillosis. Clinicians need to be aware of the potential for an interaction between such a combination.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Androstadienes; Asthma; Budesonide; Child, Preschool; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dermatomycoses; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; Humans; Iatrogenic Disease; Itraconazole; Mycetoma; Scedosporium; Skin Diseases, Infectious

A 4-year-old boy with cystic fibrosis developed hypertension, rapid weight gain and a moon face 2 weeks after starting a combined treatment of oral itraconazole and inhaled budesonide for a suspected allergic bronchopulmonary aspergillosis. Adrenal suppression was documented and found to persist 3 months after stopping this combined treatment.. To the best of our knowledge, this is the first time that an iatrogenic Cushing syndrome in a young child with cystic fibrosis after such combined treatment is reported. The inhibition of cytochrome P4503A by intraconazole and a higher glucocorticoid tissue sensitivity is suggested as the underlying mechanism.

Topics: Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Child, Preschool; Comorbidity; Cushing Syndrome; Cystic Fibrosis; Drug Therapy, Combination; Humans; Itraconazole; Male; Time Factors

Two CF patients developed Cushing's syndrome during administration of inhaled budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug co-administration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchodilator Agents; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Fatal Outcome; Female; Humans; Iatrogenic Disease; Infant, Newborn; Itraconazole; Lung Diseases; Male; Mycobacterium Infections, Nontuberculous

Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo.. This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge.

Topics: Adult; Anti-Inflammatory Agents; Aspergillosis, Allergic Bronchopulmonary; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Follow-Up Studies; Humans; Itraconazole; Risk Assessment

We report the case of an asthmatic man with HIV infection who was initially diagnosed with HIV treatment-associated lipodystrophy. Further investigations showed he had Cushing's syndrome secondary to 1600 microg of budesonide dry powder inhaler. Cushing's syndrome has not been reported previously on this normal dose of inhaled budesonide.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Budesonide; Cushing Syndrome; Diagnosis, Differential; HIV Infections; Humans; Lipodystrophy; Male; Middle Aged

A female patient was treated with high-dose inhaled fluticasone propionate for her asthma. Over 2 years, she developed features of Cushing's syndrome with proximal myopathy, osteopenia, hypertension, depressive psychosis, and cushingoid appearance. She had biochemical evidence of marked adrenal suppression with a 9:00 AM serum cortisol of 20 nmol/L that returned to normal (315 mol/L) after her therapy was changed to budenoside, 0.8 mg/d. Her appearance, mental state, and myopathy also improved with no loss of asthma control. This case illustrates the potential for developing clinically relevant adverse effects of inhaled corticosteroids when given at licensed doses.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Cushing Syndrome; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Hydrocortisone; Middle Aged

This is the first report of Cushing's syndrome under oral budesonide treatment. An 81-year-old man known for paroxysmal atrial fibrillation and chronic renal insufficiency, treated with 6 mg budesonide for collagenous colitis, developed Cushing's syndrome under co-administration of amiodarone. The Cushing's syndrome disappeared after discontinuation of the amiodarone treatment. Metabolism of the two medications by hepatic cytochrome P 450 3A may explain the development of Cushing's syndrome.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Anti-Inflammatory Agents; Atrial Fibrillation; Budesonide; Cushing Syndrome; Cytochrome P-450 Enzyme System; Humans; Male

Topics: Administration, Inhalation; Beclomethasone; Bronchodilator Agents; Budesonide; Cushing Syndrome; Humans; Pregnenediones

The Netherlands Centre for Monitoring of Adverse Reactions to Drugs received two reports of adrenal suppression, attributed to inhaled budesonide. In the first patient, a 7-year-old girl, there were growth retardation, centripetal weight gain and a Cushingoid moonface with unmeasurable serum levels of cortisol after long-term treatment with 600, and later 1000 micrograms daily. In the second patient, an 8-year-old boy, there was malaise with onset a few months after start of treatment with 400 micrograms budesonide daily. There was a lowered serum level of cortisol which returned to normal after discontinuation of budesonide. Although inhaled corticosteroids cause systemic adverse effects less frequently than orally administered corticosteroids, such effects may occur occasionally.

Topics: Administration, Topical; Adrenal Cortex; Adrenal Insufficiency; Aerosols; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cushing Syndrome; Female; Glucocorticoids; Humans; Male; Pregnenediones

Topics: Administration, Inhalation; Beclomethasone; Budesonide; Cushing Syndrome; Glucocorticoids; Humans; Male; Pregnenediones