Background Bosentan is indicated in the treatment of pulmonary hypertension. Commonly reported adverse reactions are abnormal liver function (10.9%). Purpose To evaluate the risk of hepatotoxicity associated with bosentan, comparing incidence rates with the literature. Materials and methods Retrospective observational study, including all patients with pulmonary hypertension treated with bosentan between June 2003 and April 2013. Patients with previous liver disease were excluded as well as patients referred to other hospitals. Data collected included age, sex, liver aminotransferases (AST and ALT) before and during treatment and time until liver function changed. Normal levels in men were defined as AST 0–4 U/mL and ALT 0–40 U/mL. In women AST is 0–33 U/mL and ALT is 0–32 U/mL. Results The study described 32 patients treated with bosentan, six of whom were excluded: liver damage had been observed previously in 3 patients and no data in the other 3. The other 26 were 12 men and 14 women with a median age of 65.5 years (18–87 years). Serum transaminase levels were elevated to the upper limit normal (ULN) in 10 patients (38.5%). Measures taken were: dose reduction in 1 patient (3.8%), stop treatment in 6 patients (23.0%) and no change in 3 patients (11.5%). In all of them those increases were reversible on the next liver function monitored. Patients had a mean score, before starting treatment, of AST = 19.3 U/mL and ALT = 15.9 U/mL. Average values during treatment were AST = 34.2 U/mL and ALT = 33.4 U/mL. Mean highest levels in patients with hepatotoxicity were AST = 135.7 U/mL and ALT = 145.6 U/mL. In 7, elevation of transaminases occurred during the first 26 weeks of treatment. The median time of the event was 19 weeks (4–416 weeks). The incidence of abnormal increase in hepatic aminotransaminase levels was 38.5%. Conclusions The study describes a greater incidence of hepatotoxicity associated with bosentan than described in the literature. Treatment of these cases should be adjusted. Presence of bosentan and problems with increasing liver aminotransferases are relatively common and serum concentrations should be monitored during treatment. No conflict of interest.

BackgroundThe administration of an intensive dose of statins after acute myocardial infarction (AMI) has proved to be superior to conventional doses in reducing morbidity and mortality (IA evidence) but application in clinical practice is variable.PurposeTo find out whether intensive statins doses are being used after AMI and the involvement of an emergency clinical pharmacist in this quality measure.Material and methodsThe study was conducted from February to April 2014 in an emergency room with a clinical pharmacist of a tertiary hospital. Patients with AMI were recorded and their discharge reports of hospitalisation and blood tests were reviewed. An Excel sheet with the following items was prepared: Patient sex, age, basal low density lipoproteins (LDL), intensive doses of statins after AMI (YES/NO), pharmaceutical intervention to modify the dose of statins to intensive dose (YES/NO), LDL levels at discharge, type and dose of statin scheduled in the discharge report. The target LDL levels after AMI were lower than 70 mg/dl according to clinical practice guidelines (GPC) of the European society of Cardiology (ESC) 2013.Results32 AMIs were recorded. A previous blood test including LDL levels was available in 22 patients, in 95.5% these exceeded 70 mg/dl. 84.4% of the patients received intensive doses of statins in the emergency room, 40.7% prescribed by the physician and 59.3% prescribed after a recommendation by the clinical pharmacist. At hospital discharge all patients except one were prescribed an statin. No patients were discharged with intensive doses.ConclusionThe use of intensive statins doses in the emergency room is high but It Is necessary to unify criteria at hospital discharge.The pharmaceutical recommendation to use intensive doses of statins after AMI implies an increase in compliance with evidence-based recommendations of the GPC.References and/or AcknowledgementsRev Esp Cardiol 2013;66(1):53.e1–46Circulation 2014;129:1303–09Journal of Geriatric Cardiology 2013;10:355–60No conflict of interest.

BackgroundMedication systems related to clinical decision support, when implemented in an electronic prescribing program, have the potential to reduce adverse drug reactions.PurposeTo increase safety in the prescription and administration of drugs through the introduction of new warning systems, such as of interactions, maximum doses and a guide to the parenteral administration of drugs, in an electronic prescribing programme (SILICON).Material and methods1. The most relevant interactions between the active pharmaceutical ingredients included in the pharmacotherapy guidelines (TFG) were chosen. 2. A search for the maximum dose of the active ingredients present in the parenteral administration TFG was performed. 3. The necessary information was collected in order to create a link between the proper administration and maintenance of the active pharmaceutical ingredients administered parenterally.ResultsA total of 70 interaction pairs, corresponding to 16 different active pharmaceutical ingredients, were selected and introduced in SILICON. 100% of the selected interactions were accompanied by a pharmacotherapeutic recommendation.From a total of 295 active ingredients, 140 maximum doses were considered useful for prescription and validation, and were included in SILICON. In order not to create confusion when prescribing, 28 (9%) files of active ingredients were duplicated in the program to differentiate oral and parenteral maximum doses.Finally, for the parenteral administration guide, 224 (76%) of active ingredients were selected. Moreover a direct link from the prescription screen to the administration guide was created. All active substances excluded from the guide, have an administration protocol to follow.All information entered in the prescription program was included on the pharmacy service website.ConclusionThe insertion of maximum dose alerts and interactions, and a link to the updated parenteral drugs administration guide, into an electronic administration program, provides a safety tool. In this way, we contribute towards reducing medication errors.ReferenceRivkin A, Yin H. Evaluation of the role of the critical care pharmacist in identifying and avoiding or minimizing significant drug-drug interactions in medical intensive care patients. J Crit Care 2011;26:104.e1–6No conflict of interest.

Background Antiretroviral treatment (ART) has significantly increased the life expectancy of human immunodeficiency virus (HIV)-infected individuals. However, toxicities, comorbidities and treatment failures, among others, may result in frequent ART regimen changes. Purpose To identify and analyse the ART changes and the reasons for them in HIV-infected patients over a 42-month period of study in our hospital. Materials and methods A retrospective observational study was conducted over 42 months in all outpatients on antiretroviral treatment who attended our hospital for HIV monitoring between January 2010 and June 2013. For each patient whose ART was changed we recorded the following data in a database: sex, age, previous and new treatment, reason for treatment change and resistance profile. Data was tabulated using Excel. Results During the period of study, a total of 528 patients changed ART (78% men, mean age 47 ± 7.6 years). The most common cause of change was adverse drug reactions (ADR) (47.5%). The most usual ADR were: gastrointestinal symptoms (48 patients), neuropsychiatric disorders (44 patients), renal disease (33 patients), dyslipidaemia (27 cases) and liver disease (24 cases). The drugs which caused ADR were efavirenz (8.0%), tenofovir (7.2%), atazanavir (6.3%), didanosine (6.1%) and lopinavir/ritonavir (4.4%). Other reasons for ART change were: simplification (14.6%), resistance (10.2%), treatment failure (5.5%), inclusion in a clinical trial (4.4%); and other causes (non-compliance, interactions, pregnancy, clinical decision, dose change and unknown). The most common treatment regimen before the change was tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV). After the change, tenofovir/emtricitabine (TDF/FTC) plus darunavir/ritonavir (DRV/r) was the most usual regimen. Conclusions The study revealed that a large percentage of ART changes were due to ADR. The intervention of hospital pharmacists could play an important role in the overall monitoring of HIV patients. No conflict of interest.

Background HER2 (ERB2, neu) is a proto-oncogene that encodes a transmembrane protein with tyrosine kinase activity. Trastuzumab (Herceptin), a humanised monoclonal antibody that binds to the HER2 extracellular domain, is used to treat HER2-positive breast cancer. Although it is well tolerated, it has a significant adverse effect: cardiotoxicity. Purpose To evaluate the possible effect of ERB2 gene polymorphism at codon 655 (ATC/isoleucine to GTC/valine) (rs1136201) in cardiac dysfunction related to trastuzumab in women diagnosed with HER2-positive breast cancer. Materials and methods 54 patients with HER2-positive breast cancer treated with trastuzumab in our hospital were evaluated prospectively from January to December 2012. Trastuzumab was administered as a loading dose of 8 mg/kg followed by 6 mg/kg every three weeks. For all patients, cardiac function (left ventricular ejection fraction, LVEF) was checked at baseline and every 3 months by echocardiogram or MUGA (multigated blood-pool imaging) scan. We considered cardiac toxicity if the LVEF dropped 10 percentage points from baseline and below 50%, as stated in the data sheet. For genotyping we used TaqMan probes and an allelic discrimination technique. Statistical analysis was performed with Statcalc software packages and significance was indicated by a p value lower than 0.05. Results The mean age of the patients was 51.11 ± 12.16 years. The distribution of genotypes was 55.56% AA, 40.74% AG and 3.7% GG. Of all patients, 12 developed cardiotoxicity during the treatment with trastuzumab: 4 with genotype AA, 8 with AG and none with GG. Significant correlation was not found between genotypes AA (vs. AA/GG) or GG (vs. AA/AG) and cardiac dysfunction. Instead, statistically significant differences were shown when comparing patients with genotype AG and AA/GG with cardiotoxicity (p = 0.046, OR = 4, 95% CI = 1.026–15.599). Conclusions The results of our study show an association of ERB2 polymorphism Ile655Val with cardiac toxicity associated with trastuzumab. Patients with genotype AG have higher risk of developing cardiac dysfunction related to trastuzumab than those with AA or GG. We need more studies on this polymorphism as well as larger sample sizes to confirm these findings. No conflict of interest.