fluticasone and Cushing-Syndrome

There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome.. All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted.. A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019.. The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Cobicistat; Cushing Syndrome; Drug Interactions; Fluticasone; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Male; Ritonavir

Highly effective antiretroviral treatment has improved the life expectancy of human immunodeficiency virus (HIV) infected patients, but has led to an increase in the comorbidities related to aging, such as the chronic obstructive pulmonary disease (COPD). All this implies the need for a greater number of drugs and an increasing risk of drugs interactions with antiretroviral treatment, particularly protease inhibitors.. We report a case of iatrogenic adrenal insufficiency interaction secondary to ritonavir and inhaled fluticasone in an HIV-infected patient with COPD. A review was made of the cases reported in adults in the medical literature (Medline) up to December 2012.. A total of 34 cases were reported. The mean age was 4 years. The mean dose of ritonavir was 187 mg/day, while the fluticasone dose was 866 μg/day. The average time of the interaction between ritonavir and fluticasone was 8 months. In 85% of cases fluticasone was discontinued at the time of diagnosis of adrenal insufficiency/Cushing syndrome. Almost all (90%) patients had a complete resolution of the symptoms after changing the treatment.. HIV-infected patients on antiretroviral therapy with protease inhibitor boosted with ritonavir which requires the use of inhaled corticosteroids, beclomethasone would be the best treatment option.

Topics: Administration, Inhalation; Adrenal Insufficiency; Aged; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Ritonavir

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

The purpose of this article is to provide a systematic overview of the literature on adrenal suppression and Cushing's syndrome secondary to an interaction between inhaled/intranasal fluticasone and ritonavir. The clinical presentation, diagnosis and management will be discussed.. A literature search using Medline and EMBASE and a search of abstracts of the three previous years of major HIV-related conferences were carried out.. There were 25 cases (15 adult and 10 paediatric) of significant adrenal suppression secondary to an interaction between ritonavir and inhaled fluticasone, and three cases involving ritonavir and intranasal fluticasone. Cases with other steroids were not reported; however, there were cases of adrenal suppression with itraconazole [also a potent cytochrome p (CYP) 3A4 inhibitor] and inhaled budesonide. Clinicians need to differentiate between antiretroviral-induced lipodystrophy syndrome and iatrogenic Cushing's syndrome secondary to glucocorticoid use. Long-term fluticasone and ritonavir should be avoided. If ritonavir is required, another inhaled steroid such as low-dose budesonide or beclomethasone can be used cautiously. Upon discontinuation of inhaled corticosteroids, close monitoring for symptoms of adrenal insufficiency is warranted. The need for steroid replacement therapy at physiological doses should be assessed.. The combination of ritonavir and fluticasone should be avoided. Budesonide, beclomethasone, triamcinolone and flunisolide appear to be safer options.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Child; Child, Preschool; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Infant; Male; Middle Aged; Ritonavir

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Androstadienes; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Female; Fluticasone; Glucocorticoids; HIV Protease Inhibitors; Humans; Ritonavir

Topics: Administration, Inhalation; Adult; Androstadienes; Antiviral Agents; Asthma; Biological Availability; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Drug Therapy, Combination; Fluticasone; Glucocorticoids; HIV Infections; Humans; Lopinavir; Male; Pyrimidinones; Ritonavir

Inhaled corticosteroids are generally considered safe and do not usually lead to systemic adverse events since their plasma concentrations are low due to hepatic metabolism by the cytochrome P450 3A4. However, when associated with inhibitors of this cytochrome, such as ritonavir, they may lead to iatrogenic Cushing syndrome by the systemic accumulation of corticosteroids and consequent suppression of the hypothalamic-pituitary-adrenal axis. We present a case of iatrogenic Cushing syndrome complicated by multifocal osteonecrosis in a patient with HIV infection on antiretroviral therapy with protease inhibitors boosted with ritonavir, after the association of inhaled fluticasone. This clinical case highlights a relevant interaction between corticosteroids and inhibitors of the cytochrome P450 and the severe consequences that may occur.

Topics: Administration, Inhalation; Adult; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Osteonecrosis; Pulmonary Disease, Chronic Obstructive; Ritonavir

The increase in life expectancy with the advent of highly effective antiretroviral therapy poses challenges in terms of toxicity and drug interactions. Exogenous Cushing syndrome by interaction between ritonavir and inhaled fluticasone in children diagnosed with human immunodeficiency virus infection and chronic pulmonary pathology is rare. So far, there are 20 cases reported. Three pediatric cases are reported, with a diagnosis of human immunodeficiency virus infection and chronic pulmonary pathology who presented exogenous Cushing syndrome with inhaled fluticasone at usual doses due to drug interaction between it and ritonavir. The patients resolved the clinical picture after 2-4 months of fluticasone suspension and remain asymptomatic in the follow-up.. El incremento de la expectativa de vida con el advenimiento de la terapia antirretroviral de alta eficacia plantea desafíos en cuanto a la toxicidad e interacciones medicamentosas. El síndrome de Cushing exógeno por interacción entre ritonavir y fluticasona inhalada en niños con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica es infrecuente. Hasta el momento, hay 20 casos reportados. Se describen 3 casos pediátricos con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica que presentaron síndrome de Cushing exógeno con fluticasona inhalada en dosis habituales por la interacción medicamentosa entre esta y ritonavir. Los pacientes resolvieron el cuadro clínico luego de 2-4 meses de suspensión de la fluticasona y permanecieron asintomáticos en el seguimiento.

Topics: Administration, Inhalation; Adolescent; Anti-HIV Agents; Asthma; Bronchodilator Agents; Child; Chronic Disease; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; Humans; Lung Diseases, Interstitial; Male; Ritonavir

In this paper we report a case of iatrogenic Cushing syndrome due to a pharmacological interaction between fluticasone and cobicistat. Inhaled corticosteroids were previously thought to be safe, but increasing numbers of cases of iatrogenic Cushing syndrome are being reported, especially in patients taking cytochrome P450 inhibitors, including cobicistat. Although the drug interaction between cobicistat and fluticasone has been described elsewhere, to our knowledge we present one of the first descriptions of iatrogenic Cushing syndrome due to this pharmacological interaction.

Topics: Administration, Inhalation; Cobicistat; Cushing Syndrome; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Fluticasone; Humans; Iatrogenic Disease; Male; Middle Aged

Topics: Adrenal Insufficiency; Adult; Aged; Comorbidity; Cushing Syndrome; Drug Interactions; Female; Fluticasone; HIV Infections; Humans; Iatrogenic Disease; Male; Middle Aged; Ritonavir; Steroids; Triamcinolone; Young Adult

Topics: 2-Naphthylamine; Accidental Falls; Anilides; Antiviral Agents; Bronchodilator Agents; Carbamates; Cushing Syndrome; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Hepatitis C; Humans; Hydrocortisone; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Ritonavir; Salmeterol Xinafoate; Sulfonamides; Uracil; Valine

We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months.

Topics: Adult; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Male; Nebulizers and Vaporizers; Salmeterol Xinafoate

The advent of highly active antiretroviral therapy for HIV infection dramatically changed the landscape of the disease. Ritonavir, a protease inhibitor (PI) frequently used in low doses to 'boost' the concentrations of other PIs, inhibits the cytochrome P450 3A4 isoenzyme, a common metabolic pathway to multiple drugs, so the potential for drug interactions is not negligible. A 39-year-old man with HIV-1 infection, treated with a ritonavir-boosted PI, was started on fluticasone/salmeterol inhaler and intranasal fluticasone, in 2009, in the setting of asthma and allergic rhinitis. In 2013, he presented with 1-year evolution of symptoms suggesting Cushing's syndrome, and was experiencing recurrent falls. A spine CT showed a vertical L3 fracture and thoracolumbar erosions; a bone density scan revealed severe osteoporosis. Hormonal assays were compatible with hypothalamic-pituitary-adrenal axis suppression, and iatrogenic Cushing's syndrome due to ritonavir-fluticasone interaction was considered. Fluticasone was suspended and oral corticosteroid replacement initiated, with a favourable outcome.

Topics: Accidental Falls; Adult; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Osteoporosis; Rhinitis, Allergic; Ritonavir

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Glands; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Bronchodilator Agents; Cushing Syndrome; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Middle Aged

Topics: Adrenal Insufficiency; Adult; Androstadienes; Anti-Inflammatory Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Ritonavir

Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids treatment. It can be increased by pharmacologic interactions. Glucocorticoid therapy, given in association with ritonavir, and some azole treatments are causes of iatrogenic Cushing's syndrome. We present a patient with common-variable immunodeficiency who received 7 years of itraconazole therapy for bronchial colonization with Aspergillus in combination with inhaled fluticasone without any Cushingoid symptoms. After a switch to posaconazole, the patient developed Cushingoid symptoms.

Topics: Androstadienes; Antifungal Agents; Aspergillosis; Bronchi; Bronchodilator Agents; Common Variable Immunodeficiency; Cushing Syndrome; Female; Fluticasone; Humans; Iatrogenic Disease; Itraconazole; Middle Aged; Triazoles

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

To report the rapid onset of adrenal insufficiency and subsequent development of Cushing syndrome precipitated by a CYP3A4-mediated drug-drug interaction that may have been enhanced by the presence of cystic fibrosis (CF)-related liver disease.. A 9-year-old girl with CF and cirrhosis experienced a decline in lung function that led to a diagnosis of asthma. After initiation of asthma therapy with inhaled fluticasone 110 μg/actuation, the patient experienced improvement in lung function to baseline. Seven weeks after the initiation of inhaled fluticasone, she developed vaginal candidiasis and was prescribed fluconazole 100 mg/day, a CYP3A4 inhibitor. Three days after starting fluconazole, she developed polyuria and polydipsia and was found to have severe hyperglycemia, which led to the diagnosis of Cushing syndrome. Fluticasone was discontinued, and the patient's adrenal function normalized.. Patients with CF are commonly prescribed complex medication regimens that may affect drug metabolism. CYP3A4 inhibitors may significantly decrease metabolic clearance in patients using chronic inhaled corticosteroids. Iatrogenic Cushing syndrome has been reported in patients with CF treated concomitantly, and for extended duration, with inhaled corticosteroids and CYP3A4 inhibitors. This case highlights rapid onset of adrenal insufficiency in a patient with CF-related liver disease treated briefly with a moderate CYP3A4 inhibitor. Use of the Horn drug interaction probability scale indicates that the interaction between fluticasone and fluconazole was probable.. CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Anti-Asthmatic Agents; Antifungal Agents; Asthma; Candidiasis, Vulvovaginal; Chemical and Drug Induced Liver Injury, Chronic; Child; Cushing Syndrome; Cystic Fibrosis; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Enzyme Inhibitors; Female; Fluconazole; Fluticasone; Humans; Treatment Outcome

Inhalation of fluticasone is usually devoid of systemic side-effects. The authors describe a case of a young HIV positive woman treated concomitantly with fluticasone and inhibitors of HIV protease ritonavir and lopinavir in which developed a serious endocrine side-effect - an iatrogenic Cushing's syndrome. Plasma concentration of cortisol < 5.5 nmol/l was very low (norm 250-650 nmol/l) and plasmatic ACTH was even not detectable. The administration of fluticasone and both inhibitors of HIV protease was stopped and substitution therapy with decreasing dose of hydrocortisone was initiated. Twenty weeks later resolved both clinical and laboratory symptoms of Cushing's syndrome, and the substitution therapy with hydrocortisone was terminated. Two years later became the patient pregnant and gave birth to a healthy child.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Allergic Agents; Asthma; Cushing Syndrome; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir; Young Adult

Ritonavir, a protease inhibitor (PI), is commonly used in the treatment of HIV-1 infection. It is a potent inhibitor of the hepatic cytochrome P450 superfamily. Therefore, its usage with other PI medications leads to significant increases in the levels of the latter PI, which allows a reduction in pill burden. Intranasal and inhaled corticosteroids are widely used for the treatment of allergic rhinitis and asthma. Inhaled steroids do not usually lead to systemic adverse events, since their plasma concentrations are quite low due to extensive first-pass metabolism and clearance by CYP3A4. However, the coadministration of Ritonavir with inhaled (or intranasal) corticosteroids may result in an increase in the plasma corticosteroid levels due to the potent CYP3A4 inhibition by Ritonavir. This may cause Cushing's syndrome (laboratory and clinical) with adrenal suppression.. Plasma cortisol and urinary-free cortisol levels were determined using immunoassays. In the Synacthen test, plasma cortisol levels were measured at time 0 as well as at times 60, 120, and 150 minutes following an intramuscular injection of 0.25 mg Synacthen.. We present here three HIV-1 female patients aged 12, 55 and 65 years who developed iatrogenic Cushing's syndrome with adrenal suppression following the coadministration of Ritonavir and inhaled Fluticasone, both at the standard recommended doses.. The coadministration of Ritonavir and Fluticasone at the recommended doses caused, in our three patients, iatrogenic Cushing's syndrome with adrenal suppression. We suggest that this adverse event is underdiagnosed and high clinical suspicion is needed for early diagnosis and prenention of Addisonian crises. Thus, Fluticasone treatment should be avoided in patients who are treated with Ritonavir. Alternative therapeutic options for asthma control such as oral Montelukast or bronchodilators alone should be considered.

Topics: Administration, Inhalation; Aged; Androstadienes; Antiretroviral Therapy, Highly Active; Asthma; Bronchodilator Agents; Child; Cushing Syndrome; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hydrocortisone; Middle Aged; Ritonavir

Ritonavir and atazanavir (ATZ) are protease inhibitors (PI) that inhibit the P450 3A4 cytochrome. They are used together to boost ATZ levels and reduce pill burden in human immunodeficiency virus infection, but association with medications metabolized by this cytochrome can cause serious adverse effects. Several cases of Cushing's syndrome have been reported when patients received inhaled therapy with fluticasone for asthma, sometimes complicated by secondary adrenal failure after stopping fluticasone. We report a case of Cushing's syndrome associated with onset of diabetes mellitus in a patient treated with boosted PI (ATZ and ritonavir) for HIV 2 (CD4360/ml). Asthma was treated with inhaled fluticasone 1500mug/day for several months that was stopped at admission. A few days later, typical secondary adrenal failure developed and was confirmed by dosage of cortisol and ACTH, both low. Hydrocortisone replacement treatment resulted in rapid improvement of symptoms. Diabetes was initially treated with insulin then sulfonyluraes, but repeated hypoglycemias lead to diet alone. Physicians should be aware of the potential danger of the association of "boosted" IP and some kind of inhaled corticotherapy.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Androstadienes; Blood Glucose; Bronchodilator Agents; Creatinine; Cushing Syndrome; Diabetes Complications; Diet, Diabetic; Fluticasone; Glycated Hemoglobin; HIV Infections; HIV Protease Inhibitors; HIV-2; Humans; Hydrocortisone; Male; Middle Aged; Ritonavir; Thyroxine

Fluticasone is a corticosteroid drug which is used in inhaled and nasal formulations for the treatment of asthma and allergic rhinitis. It is metabolized in the liver by the cytochrome P450. Ritonavir, an inhibitor of the HIV protease, also acts as an inhibitor of several isoenzymes of the P450 cytochrome. This property explains the many drug interactions observed with this agent.. We report two cases of Cushing's syndrome with adrenal insufficiency associated with the combined administration of oral low dose ritonavir and moderate to high dose inhaled fluticasone.. These observations highlight the fact that the combined administration of fluticasone and ritonavir must be avoided as well as the combined administration of fluticasone and other inhibitors of the cytochrome P450.

Topics: Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Protease Inhibitors; HIV Seropositivity; Humans; Iatrogenic Disease; Male; Middle Aged; 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

This case report describes an exacerbation of AIDS-associated Kaposi sarcoma (KS) in the setting of iatrogenic Cushing syndrome caused by an interaction between ritonavir-boosted atazanavir and fluticasone. Discontinuation of fluticasone resulted in resolution of the cutaneous KS. Clinicians should be aware of this potential drug-drug interaction that can result in increased corticosteroid levels. Inhaled corticosteroids should be used cautiously in persons with HIV/AIDS who have a history of KS and are being treated with a boosted atazanavir regimen because this can potentially exacerbate KS.

Topics: Androstadienes; Anti-Inflammatory Agents; Atazanavir Sulfate; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Middle Aged; Oligopeptides; Pyridines; Ritonavir; Sarcoma, Kaposi

To describe a case of Cushing syndrome in a child during concurrent use of inhaled fluticasone propionate, nasal mometasone, and a highly active antiretroviral regimen including lopinavir/ritonavir.. A 9-year-old boy with HIV infection and asthma developed moon facies, increased facial hair, and increased weight after fluticasone propionate inhalation (1 puff; 220 microg) therapy was begun. His antiretroviral regimen contained the protease inhibitor combination lopinavir/ritonavir at a dose of 216/54 mg twice daily, and he had been stable for the previous 5 years. He had also been receiving intranasal mometasone for 11 months for the management of allergic rhinitis. Serum cortisol and adrenocorticotropic hormone levels were consistent with adrenal suppression. These physical findings and symptoms and laboratory values normalized after discontinuation of the fluticasone propionate. The Naranjo probability scale indicated that a probable interaction occurred between lopinavir/ritonavir and fluticasone propionate, leading to subsequent adrenal suppression.. Protease inhibitors are associated with numerous drug interactions due to inhibition of the CYP3A4 isoenzyme. Pharmaceutical agents used to treat comorbidities in HIV-infected individuals often can interact with protease inhibitors, leading to toxic drug concentrations or untoward effects. Inhaled corticosteroids such as fluticasone propionate are often necessary to treat asthma in young children and are metabolized by CYP3A4. Interactions between protease inhibitors and inhaled fluticasone propionate have been reported in the adult population, but reports are limited in the pediatric literature.. This case raises awareness of the interaction between fluticasone propionate and lopinavir/ritonavir and adverse effects in children receiving both medications.

Topics: Administration, Inhalation; Androstadienes; Child; Cushing Syndrome; Drug Therapy, Combination; Fluticasone; Humans; Lopinavir; Male; Pyrimidinones; Ritonavir

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible.

Topics: Adolescent; Adrenal Insufficiency; Albuterol; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Atazanavir Sulfate; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; Humans; Hydrocortisone; Oligopeptides; Pyridines; Ritonavir; Salmeterol Xinafoate

Topics: Administration, Inhalation; Androstadienes; Anti-Allergic Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Asthma; Bronchiectasis; Cushing Syndrome; Drug Interactions; Fluticasone; Humans; Hydrocortisone; Itraconazole; Male; Middle Aged

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

We present 2 cases of Cushing syndrome with secondary adrenal insufficiency from concomitant use of ritonavir and inhaled corticosteroids in children with human immunodeficiency virus infection. These cases highlight the need for special consideration when treatment with an inhaled/intranasal corticosteroid is indicated in children receiving antiretroviral therapy.

Topics: Administration, Inhalation; Adolescent; Adrenal Insufficiency; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir; Salmeterol Xinafoate

Ritonavir, a potent inhibitor of CYP3A4 enzyme, can lead to high systemic concentrations of fluticasone when these 2 drugs are coadministered. Exogenous Cushing syndrome (CS) in HIV-infected patients receiving ritonavir and fluticasone has been reported frequently in adults but not in children. Three patients, all receiving ritonavir-fluticasone, developed weight gain and altered fat distribution concerning for either lipodystrophy or CS.. Three patients were initially identified by their clinicians as having weight gain and altered fat distribution concerning for either lipodystrophy or CS. All 3 patients were receiving fluticasone and ritonavir, leading to concern about a potential medication interaction. After suspecting exogenous CS, all patient medication lists were reviewed to identify all children prescribed ritonavir-fluticasone. Blood adrenocorticotropic hormone (ACTH) and cortisol were obtained during routine clinic visits. Medication history, laboratory data and physical examination findings were abstracted from medical records.. Seventeen (9%) of 189 patients in this pediatric HIV clinic had been prescribed ritonavir-fluticasone. Of 7 patients still taking ritonavir-fluticasone, CS features were present in 4 (57%) patients, including the 3 patients initially suspected of CS or lipodystrophy. Five (71%) patients, including all 4 with CS features, had low serum concentrations: median cortisol <0.2 microg/dL (normal, <0.2 microg/dL). Three of these 5 had ACTH measured, all of which were low: median ACTH 3.0 pmol/L (range, 2.2-<5.0 pmol/L). One patient taking ritonavir-fluticasone had suppressed cortisol but no CS features. The 2 patients with normal serum cortisol and ACTH values had persistent HIV viremia and were suspected of medication nonadherence. Clinical and laboratory abnormalities generally normalized in affected patients within 3 months after discontinuation of fluticasone alone (2) and ritonavir-fluticasone (3).. Pediatric HIV physicians frequently prescribe fluticasone and ritonavir together. The combination can cause CS and adrenal suppression in children, potentially leading to misdiagnosis of lipodystrophy syndrome and to increased risk of adrenal crisis during acute illness. Alternatives to fluticasone should be used for treating children receiving ritonavir.

Topics: Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Child; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; HIV-Associated Lipodystrophy Syndrome; Humans; Infant; Male; Ritonavir

Topics: Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Hydrocortisone; Male; Ritonavir

Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (

Topics: Administration, Inhalation; Adrenal Insufficiency; Adult; Androstadienes; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Male; Middle Aged; Osteoporosis; Ritonavir

Topics: Adult; Androstadienes; Anti-HIV Agents; Cushing Syndrome; Female; Fluticasone; HIV Infections; HIV-1; Humans; Puerperal Disorders; Ritonavir

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

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Androstadienes; Cushing Syndrome; Diagnosis, Differential; Fluticasone; Humans

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Cushing Syndrome; Drug Therapy, Combination; Fluticasone; Humans; Immunosuppression Therapy; Itraconazole; Lung Transplantation

The case history is presented of a patient with cystic fibrosis in whom the treatment of allergic bronchopulmonary aspergillosis with itraconazole produced an initial response but was complicated by profound adrenal shutdown and impairment of inhaled steroid clearance resulting in paradoxical Cushing's syndrome. The authors conclude that, while it is laudable to attempt to reduce the steroid burden in any patient, it is imperative that due vigilance is exercised when using a combination of agents which interact. If such a combination therapy is embarked upon, regular assessment of the pituitary adrenal axis is advisable.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cushing Syndrome; Drug Interactions; Fluticasone; Humans; Itraconazole; Male

A 45-year-old man infected with human immunodeficiency virus (HIV) developed abnormal fat accumulations that initially were believed to be caused by HIV lipodystrophy. Further clinical evaluation revealed, however, that the patient had developed exogenous Cushing syndrome, which presumably was caused by the inhibition of CYP3A4's metabolism of inhaled fluticasone by the protease inhibitor ritonavir. Clinicians should be aware that clinical clues may indicate conditions other than lipodystrophy that may cause abnormal fat accumulation and that fluticasone should be cautiously administered to patients who are receiving ritonavir.

Topics: Androstadienes; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Fluticasone; HIV; HIV Protease Inhibitors; Humans; Lipodystrophy; Male; Middle Aged; Mixed Function Oxygenases; Ritonavir

In HIV-infected patients, ritonavir, a potent cytochrome P450 inhibitor, is increasingly used to improve the pharmacokinetic profile of the associated protease inhibitor. HIV physicians are often faced with potential drug-drug interaction while treating associated diseases. We report the case of an HIV-infected patient with clinical features of Cushing's syndrome due to the interaction of low dose ritonavir with inhaled fluticasone propionate (FP). Safety of life-long CYP450 inhibition has still to be demonstrated.

Topics: Adult; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Asthma; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; Humans; Male; Ritonavir

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

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Cushing Syndrome; Female; Fluticasone; Humans; Substance-Related Disorders

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-HIV Agents; Biological Availability; Cushing Syndrome; Drug Interactions; Fluticasone; Glucocorticoids; HIV Protease Inhibitors; Humans; Male; Ritonavir

Topics: Administration, Inhalation; Adult; Androstadienes; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Depression, Chemical; Drug Therapy, Combination; Fluticasone; Glucocorticoids; HIV Infections; Humans; Male; Ritonavir