ritonavir 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

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug-drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug-drug interaction in order to suggest options for the clinical management of HIV-positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Child; Child, Preschool; Cushing Syndrome; Drug Interactions; Female; Fluocinolone Acetonide; HIV Protease Inhibitors; HIV Seropositivity; Humans; Infant; Male; Middle Aged; Ritonavir; Young Adult

Recent in vitro and in vivo studies have shown a potent inhibition of cytochrome P450 CYP3A4 through human immune deficiency virus (HIV) protease inhibitors (PIs). The PI ritonavir is described as the most potent compound within these CYP3A4 inhibitors. We present 2 cases who developed the sequelae of glucocorticoid excess following ritonavir therapy and inhalative glucocorticoid treatment: A 60-year-old HIV positive man developed the typical symptoms of Cushing's syndrome and a 52-year-old HIV positive man developed severe osteoporosis.

Topics: Administration, Inhalation; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Enzyme Inhibitors; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Male; Middle Aged; Polypharmacy; Pulmonary Disease, Chronic Obstructive; Ritonavir

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

Although in the majority of the patients with Cushing's syndrome (CS), hypercortisolism is due to ACTH hypersecretion by a pituitary tumour or to ectopic ACTH secretion from an extrapituitary neoplastic lesion or to autonomous cortisol secretion by an adrenal tumour, in occasional patients a much rarer entity may be the cause of the syndrome. Herein, we attempted to summarise and categorise these unusual causes according to their presumed aetiology. To this end, we performed a comprehensive computer-based search for unusual or rare causes of CS. The following unusual forms of CS were identified: (i) ACTH hyperesecretion due to ectopic corticotroph adenomas in the parasellar region or the neurohypophysis, or as part of double adenomas, or gangliocytomas; (ii) ACTH hypersecretion due to ectopic CRH or CRH-like peptide secretion by various neoplasms; (iii) ACTH-independent cortisol hypersecretion from ectopic or bilateral adrenal adenomas; (iv) glucocorticoid hypersensitivity; (v) iatrogenic, due to megestrol administration or to ritonavir and fluticasone co-administration. Such unusual presentations of CS illustrate why Cushing's syndrome represents one of the most puzzling endocrine syndromes.

Topics: ACTH Syndrome, Ectopic; Adrenal Gland Neoplasms; Cushing Syndrome; Female; Glucocorticoids; Humans; Liver Neoplasms; Megestrol Acetate; Ovarian Neoplasms; Pituitary Neoplasms; 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

Topics: Adrenal Cortex Hormones; Adult; Anti-HIV Agents; Cobicistat; Cushing Syndrome; Drug Interactions; Female; HIV Infections; Humans; Italy; Male; Middle Aged; Retrospective Studies; Ritonavir

We present a case report of a 62-year old female with HIV and chronic facetogenic back pain who underwent bilateral L3-L4 and L4-L5 medial branch nerve blocks using triamcinolone acetonide 80 mg. 2 weeks later she presented to the emergency department with acute anxiety/depression and was discharged with psychiatric follow-up. 2 weeks after this she presented to the outpatient HIV clinic with persistent uncontrolled depression alongside classic cushingoid features (e.g., buffalo hump, moon facies). She was diagnosed with iatrogenic Cushing syndrome caused by a drug-drug interaction between triamcinolone and ritonavir, a protease inhibitor and a CYP3A4 enzyme inhibitor. While the literature describes the interaction of ritonavir with intra-articular/intranasal/epidural triamcinolone, this is the first documented occurrence following a nerve block procedure. Symptoms resolved within 6 months alongside discontinuation of protease inhibitor therapy.. Lay abstract We report a 62-year old woman with history of HIV and depression who developed Cushing syndrome, which is a state of steroid excess in the body, after a nerve block procedure for treatment of back pain. Her first symptoms were worsening anxiety and depression, causing her to go to the emergency department. Unfortunately, the relationship to the steroids was not identified at the time. Later, she developed increased fat deposition in her face and upper neck, which is characteristic of Cushing syndrome. The HIV medications responsible for this adverse event were determined to be ritonavir and darunavir, which are classified as protease inhibitors. Her symptoms improved within 6 months in association with discontinuation of ritonavir and darunavir. This is the first known case of Cushing syndrome following a nerve block procedure for back pain, although previous cases have documented this occurrence following other forms of steroid treatments.

Topics: Cushing Syndrome; Darunavir; Female; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; 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

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

To explore the frequent interaction between antiretroviral-boosting agents and corticosteroids causing Cushing's syndrome (CS) in the French Pharmacovigilance Database (FPVD).. We conducted a retrospective case-control study describing CS recorded in the FPVD between 1996 and 2018. Case was defined as CS occurring in people living with HIV (PLWH) and control was defined as CS in uninfected individuals. Drug-drug interaction (DDI) was defined as an interaction between corticosteroids and CYP3A4 inhibitors. Data concerning the DDI, corticosteroids involved, route of administration and seriousness of the CS were described.. Among the 139 instances of CS identified, 34/35 cases (97%) had DDIs (31 with ritonavir and 3 with cobicistat) and 7/104 controls (7%) had DDIs (6 with itraconazole and 1 with verapamil). The main corticosteroid involved was inhaled fluticasone (28/35, 80%) among the cases and oral prednisone (38/104, 37%) among the controls. More CS cases (30/35, 86%) than CS controls (62/104, 60%) were serious (OR = 4.0, 95% CI = 1.4-14.4; P = 0.007).. Antiretroviral-boosting agents were responsible for one out of four iatrogenic CS cases in a French national database. Prescribers should be aware of the risk of potentially serious DDIs between antiretroviral-boosting agents and corticosteroids, including single-tablet regimens containing cobicistat.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Case-Control Studies; Child; Cobicistat; Cushing Syndrome; Databases, Factual; Drug Interactions; Female; France; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Pharmacovigilance; Retrospective Studies; Ritonavir

Cushing's syndrome after topical ocular corticosteroid use is extremely rare. We describe a case of symptomatic Cushing's syndrome in an adolescent male with sight-threatening vernal keratoconjunctivitis on antiretroviral therapy for HIV-1 infection that included ritonavir, a potent cytochrome p450 CYP3A4 inhibitor. CYP3A4 inhibition reduces the metabolism of exogenous corticosteroids leading to suppression of endogenous steroid production and Cushing's syndrome.

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Conjunctivitis, Allergic; Cushing Syndrome; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Male; Ritonavir

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

Ritonavir and cobicistat, used as pharmacokinetic enhancers in combination with some antiretrovirals (ARVs) for the treatment of HIV, are potent inhibitors of the CYP3A4 isoenzyme. Most glucocorticoids are metabolised via the CYP3A4 pathway and iatrogenic Cushing's syndrome (ICS), with possible secondary adrenal insufficiency (SAI), is a recognised complication following co-administration with ritonavir or cobicistat. A structured approach for identifying and managing potentially affected individuals has not been established.We systematically identified patients with ICS/SAI and found substantial heterogeneity in clinical practice across three large London HIV centres. While this significant drug interaction and its complications are now well-recognised, it is apparent that there is no standardised approach to management or guidance for the general physician. Here we describe the management of ICS/SAI in our current practice, review the available evidence and suggest practice recommendations.

Topics: Adult; Anti-HIV Agents; Cobicistat; Cushing Syndrome; Drug Interactions; Female; Glucocorticoids; HIV Infections; Humans; Iatrogenic Disease; Male; Medical Audit; Middle Aged; Retrospective Studies; Ritonavir

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

We report the first known case of iatrogenic cushingoid features following orbital floor triamcinolone, a synthetic corticosteroid, in a patient taking Kaletra (200 mg lopinavir/50 mg ritonavir) twice daily and Truvada (tenofovir/emtricitabine) once daily for HIV 1. Previous reports have included similar findings following epidural triamcinolone injections and with inhaled fluticasone.

Topics: Adult; Cushing Syndrome; Diagnosis, Differential; Drug Combinations; Drug Interactions; Female; Follow-Up Studies; Glucocorticoids; HIV Infections; HIV-1; Humans; Injections; Lopinavir; Orbit; Ritonavir; Tomography, Optical Coherence; Triamcinolone

Physicians are not always aware that locally administered glucocorticoids can cause systemic toxicity. This risk is greatly enhanced in the case of pharmacological interactions. We present two cases of HIV-infected patients who developed Cushing-like symptoms as a result of a pharmacological interaction. Their antiretroviral treatment regimen consisted of atazanavir, ritonavir, tenofovir and emtricitabine. One patient received salmeterol/fluticasone inhalations for asthmatic bronchitis. The other was treated with intra-articular triamcinolonacetonide injections for ongoing shoulder complaints. Ritonavir exhibits strong inhibition of hepatic enzyme CYP 3A4, which is part of the major metabolic pathway of most glucocorticoids. As a result of this interaction even locally administered glucocorticoids can cause symptoms of overdose, e.g. Cushing-like symptoms. Beclomethasone is a safe alternative for inhaled glucocorticoids as it is not metabolized by CYP 3A4. There is no substitute for intra-articular administration of triamcinolonacetonide. Depending on necessity of the administration of the drug, changing ritonavir-containing antiretroviral therapy to a non-interacting compound, e.g., an integrase inhibitor, is an option.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Combinations; Drug Interactions; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; Humans; Male; Ritonavir

The protease inhibitor (PI) ritonavir is a potent inhibitor of cytochrome P450 (CYP) 3A4 activity and frequently prescribed to boost the effectiveness of other PIs as part of highly active antiretroviral therapy. It is well established that ritonavir is capable of inducing iatrogenic Cushing syndrome (ICS) through a drug-drug interaction with inhaled fluticasone that leads to the inhibition of CYP3A activity. A rapidly increasing number of case reports are being published describing ICS induced by the interaction of ritonavir and injected corticosteroids, namely triamcinolone acetonide. A review of the current literature identified 15 cases (including the one reported here) of ICS and suppression of the hypothalamic-pituitary-adrenal axis after periradicular injection of triamcinolone acetonide. Considering an aging human immunodeficiency virus (HIV)-infected population an increasing number of patients will present with degenerative musculoskeletal disease and be seeking pain relief. Based on data reported in the literature and our own experience triamcinolone injections during ritonavir-based therapy should be avoided. After failure of all conservative therapeutic options methylprednisolone may represent a therapeutic alternative for steroid injections in HIV patients receiving PI-based antiviral therapy since it has to date not been associated with ICS.

Topics: Adult; Anti-Inflammatory Agents; Cushing Syndrome; Female; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir; Triamcinolone

Drug interactions involving human immunodeficiency virus protease inhibitors are common due to their inhibition of the cytochrome P450 3A4 isoenzyme. We describe the case of an HIV-infected patient treated with ritonavir-boosted darunavir who developed cushingoid features following an intra-articular injection of triamcinolone acetate. We review the probable mechanism for this interaction and describe similar cases of Cushing syndrome in patients receiving concomitant ritonavir and triamcinolone.

Topics: Cushing Syndrome; Darunavir; Drug Interactions; Female; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Iatrogenic Disease; Injections, Intra-Articular; Middle Aged; Ritonavir; Shoulder Pain; Sulfonamides; Treatment Outcome; Triamcinolone

Topics: Anti-HIV Agents; Anti-Inflammatory Agents; Cushing Syndrome; Humans; Iatrogenic Disease; Male; Middle Aged; Pulmonary Embolism; Ritonavir; Triamcinolone

We report two HIV-positive patients on highly active antiretroviral therapy (HAART) who developed clinical features in keeping with secondary adrenal suppression following epidural and subacromial triamcinolone. Both patients were on ritonavir-boosted protease inhibitor containing HAART and both required maintenance hydrocortisone therapy following diagnosis. This highlights the need for radiologists and clinicians practicing these injections to be aware of this complication, to elicit an accurate drug history, and to take adequate measures to minimize these adverse effects.

Topics: Adult; Anti-Inflammatory Agents; Contraindications; Cushing Syndrome; Female; HIV Infections; HIV Protease Inhibitors; Humans; Injections, Epidural; Injections, Intra-Articular; Male; Middle Aged; Ritonavir; Treatment Outcome; Triamcinolone

Topics: Cushing Syndrome; Drug Interactions; Female; Glucocorticoids; HIV Infections; Humans; Iatrogenic Disease; Injections, Epidural; Lumbar Vertebrae; Magnetic Resonance Imaging; Middle Aged; Radiculopathy; Ritonavir; Triamcinolone Acetonide

Ritonavir is a protease inhibitor (PI) frequently prescribed with highly active antiretroviral therapy. It functions to boost the effectiveness of other PIs as a result of blocking their breakdown by the cytochrome P450 (3A4) pathway. Through this same mechanism, ritonavir has been shown to cause iatrogenic Cushing's syndrome (ICS) in patients using inhaled fluticasone. In addition, a small number of recent cases suggest that ritonavir may also cause this disorder by prolonging the duration of injected corticosteroids, such as triamcinolone. This case report presents a human immunodeficiency virus (HIV) patient taking ritonavir with ICS and secondary adrenal insufficiency, presumably due to systemic absorption and decreased metabolism of an epidural triamcinolone injection. To the authors knowledge, there have only been 4 previously reported cases describing ritonavir-potentiating ICS after receiving a corticosteroid epidural. This provides further proof that caution should be taken with nonparenteral use of triamcinolone in HIV patients on PIs.

Topics: Adrenal Insufficiency; Antiretroviral Therapy, Highly Active; Cushing Syndrome; Drug Interactions; Female; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Injections, Epidural; Middle Aged; Pennsylvania; Ritonavir; Treatment Outcome; Triamcinolone

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

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 Cortex Diseases; Adrenal Cortex Hormones; Cushing Syndrome; Female; HIV Infections; Humans; Middle Aged; Ophthalmic Solutions; Ritonavir

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

Topics: Adenine; Adrenal Insufficiency; Adult; Atazanavir Sulfate; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Female; HIV Protease Inhibitors; HIV Seropositivity; Humans; Iatrogenic Disease; Injections, Intramuscular; Lamivudine; Oligopeptides; Organophosphonates; Pruritus; Pyridines; Ritonavir; Tenofovir; Triamcinolone Acetonide

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

The introduction of antiretroviral treatment with at least three active drugs has caused a substantial reduction of morbidity and mortality. Some antiretroviral drugs have the potential of interactions with other drugs. With the so called <> protease inhibitors the cytochrom-P450 inhibition by Ritonavir is used to increase the plasma level of the protease inhibitor. This strategy results in prolonged dosage intervals and reduced tablet intake due to a reduced overall dose that is needed. The interaction potential of Ritonavir originates from this cytochrom P450-inhibition. All drugs that are CYP450-metabolized can potentially be affected. Here we report two cases that were affected by the little-known interaction of Ritonavir and Triamcinolonacetonide. In both cases, Cushing symptoms emerged after infiltrations with this steroid drug in usual doses. Here we want to emphasize on this rarely encountered but potentially serious drug-drug interaction potential that is not well known to date. When initiating any new drug in HIV-Patients under antiretroviral treatment, potential interactions should be checked. The Website www.hiv-druginteractions.org is a very useful instrument for this purpose.

Topics: Adult; Anti-HIV Agents; Anti-Inflammatory Agents; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Hydrocortisone; Injections, Spinal; Male; Radiculopathy; Ritonavir; Spinal Nerve Roots; Triamcinolone Acetonide

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

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aged; Anti-Asthmatic Agents; Asthma; Child; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Female; HIV Protease Inhibitors; Humans; Incidence; Itraconazole; Male; Middle Aged; Retrospective Studies; Ritonavir; Verapamil

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

Iatrogenic Cushing syndrome with secondary adrenal insufficiency is a rare but recognized complication of intra-articular corticosteroid injection. Recent reports suggest that the risk of this serious complication is significantly higher in human immunodeficiency virus (HIV)-infected patients receiving ritonavir-based antiretroviral regimens. This article describes a case of a 44-year-old HIV-infected man taking ritonavir who required admission to the intensive care unit (ICU) for hyperosmolar hyperglycemic state following injection of triamcinolone acetonide 80 mg into his right hip for osteoarthritis. Within 3 days of the injection, he developed polydipsia, polyphagia, polyuria, fatigue, and malaise and lost 10 lbs. Laboratory evaluation revealed a blood glucose of 766 mg/dL, and serum pH was 7.36 (normal, 7.31-7.41). After 3 days in the ICU, he was discharged on detemir insulin 15 units subcutaneously daily and sliding scale insulin aspart. Seven weeks after the injection, his detemir insulin had been titrated to 41 units daily, and his serum triamcinolone acetonide concentration was 0.39 mcg/dL (normal, <0.03 mcg/dL). His morning plasma cortisol level was 1.6 mcg/dL (normal, 4-24 mcg/dL), and his adrenocorticotropic hormone concentration was <5 pg/mL (normal, 7-50 pg/mL), consistent with suppression of his hypothalamic-pituitary-adrenal axis. We believe that systemic absorption of triamcinolone and decreased metabolism of triamcinolone due to ritonavir caused this profound and persistent hyperglycemia and hypothalamic-pituitary-adrenal axis suppression. This case highlights the need for heightened awareness of potential interactions to avoid important adverse effects in patients who receive intra-articular corticosteroids.

Topics: Adult; Cushing Syndrome; Hip Joint; HIV Infections; HIV Protease Inhibitors; Humans; Injections, Intra-Articular; Male; Ritonavir; Triamcinolone

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

The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary adrenal failure remains an exceptional event after a single dose administration of a synthetic glucocorticoid. Medical attention has been drawn recently on the possible impact of ritonavir-based antiretroviral regimens on the systemic deleterious effects of a chronic administration of corticosteroids in HIV-infected patients. Three HIV-infected patients treated by a ritonavir-boosted protease inhibitor (PI) regimen received a single intra-articular injection of 40 mg triamcinolone acetonide in our university hospital. The three patients rapidly developed signs and symptoms of ICS followed by secondary adrenal insufficiency. Special attention must be paid when a single administration of corticosteroids has to be given in HIV-positive patients under ritonavir-boosted antiretroviral treatment, as these patients are at risk of developing early cushingoid features and a prolonged suppression of their hypothalamic-pituitary-adrenal axis.

Topics: Adrenal Insufficiency; Cushing Syndrome; Female; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Injections, Intra-Articular; Male; Middle Aged; Ritonavir; Triamcinolone Acetonide

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Cushing Syndrome; Drug Combinations; Drug Interactions; Female; Fluticasone-Salmeterol Drug Combination; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Ritonavir

We report the first case of a human immunodeficiency virus type 1 (HIV-1)-infected individual receiving combination antiretroviral therapy, which included ritonavir, who developed Cushing syndrome with profound complications after epidural triamcinolone injections. This case highlights the potential of ritonavir interactions even with local injections of a corticosteroid.

Topics: Adult; Cushing Syndrome; Drug Interactions; HIV Infections; HIV-1; Humans; Iatrogenic Disease; Lopinavir; Male; Pyrimidinones; Ritonavir; Triamcinolone

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; 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

Topics: Bone Resorption; Cushing Syndrome; Drug Administration Schedule; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Prednisone; Ritonavir; Steroids

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

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

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