BackgroundIn Cushing’s syndrome (CS), when surgery is unsuccessful or contraindicated, ketoconazole is the drug most frequently used to treat hypercortisolism.In July 2013, European Medicines Agency announced their negative risk-benefit assessment of oral ketoconazole as treatment of fungal infections, because it can cause liver damage and drug interactions due to cytochrome P450 inhibition. Ketoconazole was suspended as an antifungal in the European Union, but compassionate use is authorised for CS.PurposeTo analyse the hormonal effects and tolerance of ketoconazole in CS over the last year.Material and methodsNine patients [32–83 years old] were treated in hospital. All patients were retrospectively studied with a follow-up of 26 months; their treatment had lasted from 12 days–25 years. One patient had ectopic ACTH production, two had pituitary adenoma, and six had adrenal neoplasia. Four patients had previously had surgery, but it was not effective in two cases. The dose of ketoconazole was between 200–1,200 mg/day.Liver tests checked: transaminases, total bilirubin and alkaline phosphatase. Hormonal control was observed with Nugent’s test and 24 h urinary free cortisol. The patient’s current treatment was noted to check for drug interactions.ResultsAll patients were checked. No adrenal insufficiency was observed. Liver function tests were normal. Five patients stopped ketoconazole: two for surgery; two died of metastatic cancer; and one because of a potential drug interaction with calcium antagonism. 77.8% of the patients had some possible drug interactions, but only one stopped ketoconazole. Other interactions were with drugs metabolised by CYP450; or with proton pump inhibitors which reduce the pH-dependent absorption of ketoconazole. These problems were solved by changing the dose of the drugs concerned.ConclusionKetoconazole seems to be a safe and efficacious treatment in CS. However, it is necessary to perform a bigger study to get significant conclusions.ReferenceFeelders RA, Hofland LJ, de Herder WW. Medical treatment of Cushing’s syndrome: adrenal-blocking drugs and ketoconazole. Neuroendocrinology 2010;92(Suppl 1):111–15No conflict of interest.
BackgroundPleural aspergillosis (PA) was first described in 1842 but remains a relatively rare entity when compared with other Aspergillus infections.PurposeTo describe the pharmacological management of a patient diagnosed with PA and the efficacy of intracavitary instillation of amphotericin B (ICAB) treatment.Material and methodsA 32-year-old woman with multiple drug allergy syndrome (NSAIDs, pyrazolones, quinolones, lincosamides, SSRIs, ondansetron) was admitted to our hospital because of postoperative Pseudomonas pneumonia complicated with empyema and bronchopleural fistula. The patient underwent thoracostomy. Pleural biopsy showed septate fungal hyphae and pleural fluid culture grew Aspergillus fumigatus while serum galactomannan antigen was negative. Systemic antifungal therapy, with oral voriconazole at first and then with posaconazole, was started. Concurrently, amphotericin B deoxycholate, diluted in 75 ml of 5% glucose solution, was infused directly into the pleural cavity, at 5 mg on the first day, rising to 10 mg and 25 mg on the second and third day, respectively, and then 50 mg, after washing of the pleural cavity with 5% glucose solution. Daily dressing with amphotericin B-impregnated gauze was introduced in the cavity. Local treatment was continued for about two weeks.ResultsThe treatment was well tolerated with no adverse drug reactions. The symptoms and the physical signs improved greatly during hospitalisation and the patient left the hospital 3 days after the end of treatment. Repeat pleural fluid culture was negative 2 weeks after the end of treatment.ConclusionICAB may improve the efficacy of systemic antifungal therapy and it should be considered as an additional treatment option. Moreover, the use of this method avoids repeated needling of the cavity and may allow extended treatment on a domiciliary basis.ReferenceKravitz JN, Berry MW, Schabel SI, et al. A modern series of percutaneous intracavitary instillation of amphotericin B for the treatment of severe hemoptysis from pulmonary aspergilloma. Chest 2013;143(5):1414–21No conflict of interest.
BackgroundHepatitis C is a serious disease with a high prevalence, being the leading cause of liver transplantation. There is now rapid development of new drugs for this disease. During the period of this study, only the following anti-hepatitis C agents were available: peg-interferon, telaprevir, boceprevir, simeprevir, sofosbuvir daclatasvir and ribavirin.PurposeTo analyse the effectiveness of sofosbuvir associated with other antiviral against hepatitis C, and identify adverse reactions produced.Material and methodsA descriptive study including patients that started therapy with sofosbuvir from August 2014 to January 2015. Data collected were: viral genotype, treatment duration with sofosbuvir and negativisation time to viral load.ResultsDuring the study period, 37 patients began treatment with sofosbuvir. Of these, 28 had genotype 1b (17 were treated for 12 weeks and 11 during 24 weeks), 3 had genotype 1a, 2 had genotype 3 and 4 had genotype 4. Patients with genotypes 1a and 4 were treated for 12 weeks and those with genotype 3 for 24 weeks.With respect to treatment for 12 weeks, the associations used most were sofosbuvir with simeprevir and ribavirin in 65.22% of patients. This was also the most prescribed combination in patients with genotype 1b, being used in 11.45.5%. Genotype 1b patients treated with this combination had a rapid virological response (RVR), which means an undetectable viral load in week 4 of treatment.In the 24 week treatment, 76.92% of patients (10 patients) received sofosbuvir with daclatasvir. Of these patients, 9 had genotype 1b. 55.5% of patients with genotype 1b and the above combination had a RVR.37 patients had undetectable viral load at the end of treatment. All patients achieved a sustained viral response at 4 weeks post-treatment (SVR4), and also showed a sustained viral response at 12 weeks post-treatment (SVR12), which means cure.ConclusionIn our patient population, using sofosbuvir associated with other antihepatitis C drugs available at the time of the study, helped to reduce the time required to neutralise the viral load, and present a good safety profile, which can improve adhesion.References and/or AcknowledgementsGutierrez JA, Lawitz EJ, Poordad F. Interferon-free, direct-acting antiviral therapy for chronic hepatitis. J Viral Hepat 2015No conflict of interest.
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