Gloria Manso

Hepatotoxicity Induced by Antiandrogens: A Review of the Literature

Introduction: Hepatotoxicity is a serious adverse reaction potentially induced by all antiandrogens. We have reviewed here the published cases of hepatotoxicity induced by steroidal and nonsteroidal antiandrogens, and compared the type and characteristics of liver damage. Methods: Using two different databases: MEDLINE and IDIS (Iowa Drug Information Service), we searched for published cases of liver injury induced by antiandrogens. Analysis was made of the type of hepatotoxicity, therapeutic indication, other pharmacological treatments and evolution. Mean values of latency and recovery periods of the adverse reactions and liver function tests were also evaluated. Results: Hepatitis was the most common type of hepatotoxicity reported, and was associated with all antiandrogens. This adverse reaction does not seem to be dependent on the patients age, therapeutic indication or the dose prescribed. Hepatitis showed a longer latency period for cyproterone acetate than for flutamide. Some transaminase levels were significantly higher for flutamide than for cyproterone acetate, although the evolution was no worse in the cases reported for flutamide. We also found occasional reports of hepatocellular carcinoma and hepatic cirrhosis suspected of being induced by cyproterone acetate. Conclusion: Although there are differences in the clinical features of hepatotoxicity induced by steroidal and nonsteroidal antiandrogens, these do not predict which patients will develop hepatotoxicity during treatment or evolution. Serial liver function tests are required for early detection of liver damage.

Continuous reporting of new cases in Spain supports the relationship between Herbalife® products and liver injury.

Previous publications have linked Herbalife® products to hepatotoxicity. The identification of earlier cases in which the culprit agent could not be established raised the hypothesis of a possible contamination of some specific batches of Herbalife products.

Safety profile of proton pump inhibitors according to the spontaneous reports of suspected adverse reactions.

OBJECTIVE [corrected] To evaluate similarities and differences in safety among proton pump inhibitors (PPIs) under the usual conditions of prescription. METHODS A search of spontaneous reports on adverse reactions associated with these drugs and registered between January 1, 2004 and December 31, 2004 was undertaken in the Spanish Pharmacovigilance System Database. We compared the frequency of reports with the consumption of PPIs, and analyzed the organ and system distribution for each PPI. Of the organ and system groups more commonly affected, diarrhea, myalgia, abnormal vision and hepatitis were selected for further analysis. RESULTS Nearly 8 times more reports for omeprazole compared to other drugs were found but a similar difference was observed in their consumption. Skin and appendage disorders were more frequently reported for omeprazole and rabeprazole, the urinary, female reproductive and endocrine systems for lansoprazole, musculoskeletal for omeprazole and esomeprazole, vision for pantoprazole, rabeprazole and esomeprazole, gastrointestinal tract for omeprazole and lansoprazole and liver and biliary systems for omeprazole, lansoprazole and pantoprazole. Myalgia appears more often in younger patients than diarrhea, abnormal vision or hepatitis and shows longer periods of latency and recovery. The four adverse reactions analyzed were mainly reversible. CONCLUSION A direct relationship was found between consumption and the number of reports. Some organ and system groups were affected by more than one PPI and this showed a specific pattern of group toxicity to these pharmacological agents. Some reports involved only lansoprazole and these require further analysis.

Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab†

The aim of this study was to analyse the suspected adverse reactions associated with rituximab or trastuzumab reported to the Spanish Pharmacovigilance System.

Trends in the pharmacological treatment of osteoporosis in Spain from 2000 to 2008.

AIM To analyze the time trends in anti-osteoporosis medications consumption in Spain between 2000 and 2008 and the influence on such consumption induced by the Information Sheets related to the safety of menopausal hormone therapy and strontium ranelate published by the Spanish Agency of Medicines and Health Products (AEMPS). METHODS Purchase data of anti-osteoporosis medications from 2000 to 2008 were obtained from the Spanish Ministry of Health. This information includes the pharmacy sales data of medicinal products reimbursed by the Spanish National Health Service. Anti-osteoporosis medications consumption data were expressed as defined daily dose per 1 000 inhabitants per day in women aged 50 or more. RESULTS During the study period, anti-osteoporosis medications consumption showed a continuous increase. The greatest increase was observed with bisphosphonates, particularly alendronate and risedronate in their weekly formulations. Strontium ranelate consumption was low but continuously increased and new information concerning its safety in 2007 had no effect on its consumption. The use of menopausal hormone therapy remained stable until 2003, and from then presented a continuous decrease until 2008. Raloxifene utilization increased from 2000 to 2004 and decreased thereafter. Calcitonin utilization decreased uninterruptedly and teriparatide was infrequently used. CONCLUSION This study reports a marked change in osteoporosis treatment in Spain, which includes an important increase in anti-osteoporosis medication use, particularly of bisphosphonates and a decrease in menopausal hormone therapy use secondary to the new information about their safety.

Criterios de Beers versus STOPP en pacientes mayores, polimedicados y residentes en la comunidad

OBJECTIVE To assess potentially inappropriate prescribing (PIP) using Beers (2012 version) and STOPP (2008 version) criteria in polypharmacy, community-dwelling, older patients. METHODS From the information collected in the invoicing data of the prescriptions and the electronic medical records, a sample was selected of 223 ≥ 65-year-old patients who were taking simultaneously 10 or more drugs per day. Beers and STOPP criteria were separately applied, and the results obtained with the two methods were compared. RESULTS A total of 141 (63.2%) patients presented at least one Beers criterion. The two most frequently observed Beers criteria independent of diagnosis were the use of benzodiazepines and the use of non-COX-2-selective non-steroidal anti-inflammatory drugs. With regard to Beers criteria considering diagnosis, the most frequent were the use of anticholinergic drugs in patients with lower urinary tract symptoms or benign prostatic hyperplasia, and the use of benzodiazepines, antipsychotics, zolpidem or H2-antihistamines, in patients with dementia or cognitive impairment. A total of 165 (73.9%) patients had at least one PIP according to the STOPP criteria. Duplicate drug classes and long-term use of long-acting benzodiazepines were the two most frequent STOPP criteria. DISCUSSION Our study identified a high frequency of PIP in polymedicated community-dwelling older patients. Simultaneous application of Beers and STOPP criteria represents a useful tool to improve prescribing in this population group.

La notificación directa por los pacientes de reacciones adversas a medicamentos en España

The Spanish Pharmacovigilance System for Medicinal Products for Human Use, integrated by regional centers of pharmacovigilance coordinated by the Spanish Agency for Medicines and Health Products, is responsible for developing the Program of Spontaneous Reporting of Suspected Adverse Drug Reactions in our country. Although, until now, reports were only requesting to health professionals, the current understanding of the role of patients in the clinical setting and the experience gained in other countries of our environment, have demonstrated the convenience of developing active participation systems to patients in the reporting of suspected adverse drug reactions. In addition, this is taking into account in the new European legislation on pharmacovigilance.

Inappropriate prescribing in polypharmacy elderly outpatients taking multiple medications. Are the STOPP criteria useful

OBJECTIVE To assess potentially inappropriate medications (PIMs) in elderly outpatients taking multiple medications. METHODS Invoicing data of the prescriptions and electronic medical records were used to apply the STOPP (screening tool of older peoples prescriptions) criteria. RESULTS Three out of 4 patients included in the study received PIMs. The most common criteria found were: duplicate drug class prescriptions (n = 58 (17.4%)), long-term long-acting benzodiazepines (n = 54 (16.2%)), and acetylsalicylic acid with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (n = 32 (9.6%)). CONCLUSION Our results highlight the relevance of the systematic review of the pharmacological treatments in these patients.

Reporting problems related to medications in Spain. The yonotifico (I report) project, an option for citizens.

Sir, – The new European legislation concerning pharmacovigilance published in 2010 promotes the involvement of patients in spontaneous reporting programs of suspected adverse drug reactions (ADR) [1]. To facilitate this involvement, regulatory agencies of the European Union member states should develop websites for the electronic reporting by citizens; it should be the initiative of each country to develop paper formats and additional reporting systems, such as telephone, fax, or e-mail [2, 3]. In January 2013, the Spanish Agency of Medicines and Medical Devices (AEMPS) set up a website including an electronic form for direct reporting by citizens of suspected ADR (www. notificaram.es). In this way, the AEMPS is enforcing the new legislation and provides the Spanish population with the possibility of reporting ADRs and collaborating with the existing pharmacovigilance system [4]; the Spanish agency has not implemented additional reporting systems for citizens so far.

Los criterios STOPP/START más frecuentes en España. Una revisión de la literatura

OBJECTIVE To analyse STOPP/START criteria found most frequently in the studies carried out in Spain, in order to identify the main areas of potentially inappropriate prescribing. METHODS A literature review was carried out on the original studies performed in Spain that applied the original version of the STOPP/START criteria and that described the most common STOPP and/or START criteria found. In each study, a weighted analysis was performed on the criteria found, by assigning 5 points to the criterion in first position, 4 points to the criterion in second position, and so on to fifth criterion. The total points of each analysed criterion were then obtained. RESULTS A total of 19 original studies analysing STOPP criteria were selected, 14 of them also studying all START criteria. From the total of studies, 11 were developed in out-of-hospital care, and 8 in hospital care. The STOPP criterion with the highest weighted assessment was B7 (long-term, long-acting benzodiazepines), followed by J (any duplicate drug class prescription). The START criterion with the highest weighted assessment was F4 (statin therapy in diabetes mellitus if coexisting major cardiovascular risk factors present), followed by E3 (calcium and vitamin D supplement in patients with known osteoporosis: previous fragility fracture, acquired dorsal kyphosis). CONCLUSIONS The most common areas of potentially inappropriate prescribing are well defined, and suggest a particular intervention in some specific therapeutic points.