pulmicort and HIV-Infections

Cytochrome P450 3A (CYP3A) is involved in biotransformation of more than half of all drugs currently available. Drug interactions by inhibition of CYP3A are of major interest in patients receiving combinations of drugs. Some interactions with CYP3A inhibitors also involve inhibition of the multidrug export pump, P-glycoprotein. An increasing number of adverse drug reactions might be avoided on the basis of knowledge about CYP3A substrates and inhibitors. This article summarizes some examples of such interactions relevant to gastroenterologists. Serious cases by coadministration of CYP3A inhibitors resulting in acute hepatitis, hypotension, rhabdomyolyis, torsade de pointes, sedation, or ergotism are presented: interactions with azole antifungals (ketoconazole, itraconazole, fluconazole), HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir), macrolide antibiotics (clarithromycin, erythromycin), and grapefruit juice. In addition, 1 case is reported who presented the highest trough levels of the CYP3A substrate budesonide in serum ever measured. Practitioners have to be aware of the high potential of metabolic drug interactions when they prescribe a CYP3A inhibitor. It is wise to check carefully comedication in patients complaining of side effects with substrates of CYP3A.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Aryl Hydrocarbon Hydroxylases; Beverages; Budesonide; Citrus paradisi; Cytochrome P-450 CYP3A; Drug Interactions; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Oxidoreductases, N-Demethylating

Topics: Administration, Inhalation; Adrenal Insufficiency; Aged; Asthma; Bronchodilator Agents; Budesonide; HIV Infections; HIV Protease Inhibitors; Humans; Male; Ritonavir; Withholding Treatment

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

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

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

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

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

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

Topics: Acute Disease; Adult; Alanine Transaminase; Anti-Inflammatory Agents; Anus Neoplasms; Aryl Hydrocarbon Hydroxylases; Budesonide; Carcinoma, Squamous Cell; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Middle Aged; Oxidoreductases, N-Demethylating; Ritonavir

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

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