Safety Patient

Cardiac Science Powerheart, CardioVive, CardioLife; GE Responder and Responder Pro; and Nihon-Kohden Automated External Defibrillators

2012-03-03T04:02:00.000-08:00

Cardiac Science Powerheart, CardioVive, CardioLife; GE Responder and Responder Pro; and Nihon-Kohden Automated External Defibrillators (AEDs): Class I Recall - Defective Component

Affected Models include:

Powerheart 9300A, 9300E, 9300P, 9390A, and 9390E
CardioVive 92532, 92533
CardioLife 9200G and 9231
GE Responder and Responder Pro
Nihon-Kohden AEDs

AUDIENCE: Emergency Medicine, Cardiology, Risk Manager

ISSUE: FDA notified healthcare professionals and medical care organizations of the Class 1 recall of the listed AEDs which contain a component that may fail unexpectedly due to a defect. If the component were to fail during a rescue attempt, the AED may not deliver defibrillation therapy, causing serious adverse health consequences, including death. The unit’s self test may not detect the failure or impending failure of the component.

BACKGROUND: These products are used for emergency treatment of victims showing symptoms of sudden cardiac arrest who are unresponsive and not breathing. These AEDs were manufactured and distributed from July 1, 2011 through December 30, 2011.

RECOMMENDATION: Affected customers are advised to contact the firm to arrange for delivery of shipping materials for an immediate return of their AEDs for repair. The affected devices will receive a hardware correction, and the same serial number device will be returned to the customer in most cases.

Read the MedWatch safety alert, including links to the Recal Notice and Letter, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm294538.htm

Fingolimod (Gilenya°): European Medicines Agency's lack of transparency spells danger for patients

2012-02-28T19:37:00.000-08:00

Fing

Disclosure: the editor of this blog, has been perfomed and Health Evaluation Thecnology Assessment for Novartis, in 2011. Phase III studies shows heart blocks and no one death. Eventhough Novartis has established a politic of control of at least 6 hours in a medical center. This policie is being supported by Novartis, at least in Argentina. The last pessure has shown that over almost 30K patients in treatment with the drug, just only one person died, and the conditions were no that the Novartis deals. I've signed a contract without restrictions to any relevant information. In spite of the prescrire statement, and I agree more studies are needed, but the quality of life is the strongest issue, being the first oral treatment that really equation risk/benefit is good enough (at the state of art today) in multiple sclerosis. This statement has been written in order to encourage to all researchers, all over the world to declare their interest conflicts. The original paper has not been published yet. It has been writen in spanish, and my compromise is to ask to allow to Novartis to be published.

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Fingolimod (Gilenya°): European Medicines Agency's lack of transparency spells danger for patients

The European Medicines Agency (EMA) has refused to supply Prescrire with the detailed data in its possession on cases of death which occurred following the first dose of fingolimod (Gilenya°). This lack of transparency spells danger for patients.

Fingolimod (Gilenya°) is an immunosuppressant which has been authorised since March 2011 by the European Medicines Agency (EMA) for certain patients with multiple sclerosis. The pre-marketing evaluation data already revealed cardiac arrhythmia, among other disorders. In April 2011 Prescrire recommended limiting use of fingolimod to rigorously supervised clinical trials.

In December 2011, the US Food and Drug Administration (FDA) reported the sudden death of a patient within the first 24 hours of taking fingolimod. On 22 December 2011, in response to the FDA alert and faced with EMA’s silence, Prescrire asked EMA for a review of the serious adverse effects of fingolimod, and for the initial European Periodic Safety Update Report (PSUR), which must be filed with EMA within 6 months of the marketing authorisation, i.e. in September 2011.

It was not until 20 January 2012 that the European Agency issued a public announcement on the subject, stating that there had been 3 other sudden deaths and 3 unexplained deaths. Three days later, on 23 January 2012, just 34 minutes before the legally mandated deadline, EMA informed Prescrire that its request for information dated 22 December was rejected, on the grounds that a European re-evaluation of fingolimod was under way: the re-evaluation had been initiated 3 days earlier.

On 7 February 2012, Prescrire reiterated its information request, this time to EMA Director Guido Rasi, vigorously contesting EMA’s grounds for refusal. As of 17 February 2012, EMA’s Director has not replied to Prescrire.

Once again the European Agency is refusing to provide patients and healthcare professionals with important information on adverse effects after the drug has come onto the market, information that is itself the fruit of the reporting work carried out by patients and healthcare professionals.

In May 2011, EMA had already invoked a re-evaluation under way to justify its refusal to provide Prescrire with information on pioglitazone (Actos°), which increases the frequency of bladder cancer and is no longer reimbursed by France’s national health insurance system. The European Commission has maintained the marketing authorisation for pioglitazone.

In early 2012, the European Medicines Agency and the European Commission’s Directorate General for Health and Consumers are behaving just as they did before the Mediator° fiasco. They give the benefit of the doubt to drug companies rather than to patients, and dispense information about adverse effects only sparingly. It is high time that they get back to their primary mission: protecting patients’ health, which should take precedence over protecting the financial interests of pharmaceutical companies.

©Prescrire 20 February 2012

Sigmoid Perforation in Association with Colonoscopy

2012-02-22T17:44:00.000-08:00

Sigmoid Perforation in Association with Colonoscopy

Albert Lu, M.D., and Paul Aronowitz, M.D.

N Engl J Med 2012; 366:744February 23, 2012

Slide

Article: A 74-year-old woman was undergoing a screening colonoscopy when it became apparent that the rectosigmoid junction might have become perforated. The procedure was terminated, and radiographs were obtained. The abdominal radiograph (Panel A) revealed retroperitoneal free air outlining the right kidney (white asterisk) and psoas muscles (black asterisks). The inferior edge of the liver was outlined by air (arrow), a feature consistent with intraperitoneal free air. A chest radiograph obtained with the patient in the upright position (Panel B) showed free air under the diaphragm (black arrows), right pneumothorax (white arrow), pneumomediastinum (arrowhead), and subcutaneous emphysema. In this case, a 1-cm perforation in the distal sigmoid, near the rectosigmoid junction, allowed air to track into the intraperitoneal and retroperitoneal spaces. Thus, pneumomediastinum, pneumothorax, and subcutaneous emphysema can on rare occasions occur after colonic perforation. The patient was taken to the operating room, where a successful repair of the sigmoid colon was performed. She was discharged 1 week later in good condition.
Albert Lu, M.D.
Loma Linda University, Loma Linda, CA
allu@llu.edu
Paul Aronowitz, M.D.
California Pacific Medical Center, San Francisco, CA

Adverse drugs events in US adult ambulatory

2012-02-19T10:29:00.000-08:00

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Adverse drug events in U.S. adult ambulatory... [Health Serv Res. 2011] - PubMed - NCBI

Health Serv Res. 2011 Oct;46(5):1517-33. doi: 10.1111/j.1475-6773.2011.01269.x. Epub 2011 May 10.

Adverse drug events in U.S. adult ambulatory medical care.

Sarkar U, López A, Maselli JH, Gonzales R.

Source

Department of Medicine, UCSF Center for Vulnerable Populations, San Francisco General Hospital Medical Services, Division of General Internal Medicine, University of California, San Francisco (UCSF), Box 1364, 1001 Potrero, Bldg 10, 3rd Floor, San Francisco, CA 94143-1364, USA. usarkar@medsfgh.ucsf.edu

Abstract

OBJECTIVE:

To estimate the incidence of adverse drug events (ADEs) associated with health care visits among U.S. adults across all ambulatory settings.

DATA SOURCE:

We analyzed data from two nationally representative probability sample surveys: the National Ambulatory Medical Care Survey and the National Hospital and Ambulatory Medical Care Survey. From 2005 to 2007, the presence of an ADE was specifically defined, requested, and recorded in these surveys.

STUDY DESIGN:

Secondary data analysis.

PRINCIPAL FINDINGS:

An estimated 13.5 million ADE-related visits occurred between 2005 and 2007 (0.5 percent of all visits), the large majority (72 percent) occurring in outpatient practice settings, and the remaining in emergency departments. Older patients (age ≥65 years) had the highest age-specific ADE rate, 3.8 ADEs per 10,000 persons per year. In adjusted analyses of outpatient visits, there was an increased odds of an ADE-related visit with increased medication burden (odds ratio [OR] for six to eight medications compared with no medications, OR 3.83 [2.20, 6.65]), and increased odds of ADEs associated with primary care visits compared with specialty visits (OR 2.22 [1.70, 2.89]).

CONCLUSIONS:

Approximately 4.5 million ambulatory visits related to ADEs occur each year, the majority of these in outpatient office practices. A greater focus on ADE prevention and detection is warranted among patients receiving multiple medications in primary care practices.
© Health Research and Educational Trust.

PMID:: 21554271; [PubMed - indexed for MEDLINE]
PMCID:: PMC3168717; [Available on 2012/10/1]

Adverse drug events in U.S. adult ambulatory... [Health Serv Res. 2011] - PubMed - NCBI

More Evidence Reveals JIA Treatment Isn’t Cause of Cancer Risk

2012-02-13T19:36:00.000-08:00

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Source: http://goo.gl/rq94x

New data shows kids with juvenile idiopathic arthritis have four times the cancer risk and treatment doesn’t appear to be to blame.

By Jeanie Lerche Davis

2/13/12 A new study creates a deeper understanding of the link between juvenile idiopathic arthritis, or JIA, its treatment and cancer risk: It found that treatment with tumor necrosis factor-alpha inhibitors – a type of biologic – does not appear to increase a child’s risk of cancer. But it also found that children with JIA have a more than four times higher cancer risk compared to children without JIA – an elevated risk that doctors stress is still very small, overall.
JIA, the most common type of arthritis seen in children, affects an estimated 294,000 kids in the United States; there are several subtypes, based on the disease’s severity and number of joints affected. Because many of the most effective drugs – including biologics – can carry some pretty hefty side effects, and patients are often put on more than one drug, treating JIA can lead some parents to wonder if the treatment is worse than the disease.
Anti-TNFs and Black Box Warnings
The first biologic drug to be FDA-approved, in 1998, was etanercept, or Enbrel, a tumor necrosis factor-alpha inhibitor – alternately called TNF inhibitor or anti-TNF. It gained approval for JIA in 1999. Etanercept, like the other anti-TNFs that followed, works by supressing parts of the immune system, which goes awry and attacks a person’s own body in autoimmune conditions like rheumatoid arthritis, or RA, as well as ankylosing spondylitis, psoriatric arthritis and JIA.
In 2009, amid case reports of cancer among children and adolescents using anti-TNFs, the FDA issued a “black box” warning stating that “lymphomas and other malignancies” have been reported in those treated with anti-TNFs.
But whether anti-TNFs are linked to a higher risk of cancer, among both adults and children, is a controversial issue: large analyses, one published in 2009 and two in 2011, found no increased risk of cancer with TNF inhibitors yet, a meta-analysis published in September 2011 linked TNF inhibitors to a higher incidence of skin cancer, but not to an increase in the risk of other cancers, in adult RA patients.
Good News and Bad News for Parents
The newest study, finding that anti-TNF use in children with JIA does not appear to be linked to a higher cancer rate, is published in the Feb. 13, 2012 issue of Arthritis & Rheumatism. The data were originally presented at the 2010 American College of Rheumatology Annual Scientific Meeting.

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Global storage conditions for medicines

2012-02-12T06:03:00.000-08:00

i take drugs (Photo credit: the|G|™)

E-DRUG: Global storage conditions for medicines
------------------------------------------

'Must not be stored above 25oC'

This storage instruction has begun to appear on tablet packages from many manufacturers, some of them large generic companies. An adverse effect of this instruction is that some patients in Norway put their tablets in the fridge in the summer heat. Fridges have high humidity, are often crowded and dirty and full of fungus, and are definitely within sight and reach of children.

The big problem is not that the storage instruction is misinterpreted. The problem is that neither WHO nor medicine authorities do require or recommend manufacturers to make medicines that can be stored at higher temperatures. Medicine storage regulations are not in harmony with the living conditions of people in warm countries.

ICH test conditions are 24oC/60%RH until claimed shelf life, and 40oC/75%RH for typically 6 months. Manufacturers will not test at high temperatures or long periods if there is no money in it, or if they are not forced to.

We need medicines that can be stored at 35 or 40oC for a long shelf life without damage.

A lot of today's medicines can probably stand that challenge, but the evidence for that is not there yet.

The World Health Organisation, WHO, the International Committee of Harmonisation, ICH, the International Pharmaceutical Federation, FIP, and regulatory authorities in all countries - unite and solve this problem!

Stein Lyftingsmo
Hospital Pharmacy of Elverum, Norway
www.lyftingsmo.no
"Stein Lyftingsmo" <stein@lyftingsmo.no>

Victrelis (boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV)

2012-02-09T11:48:00.000-08:00

Victrelis (boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV) Protease Inhibitor Drugs: Drug Safety Communication - Drug Interactions

AUDIENCE: Infectious Disease, Pharmacy

ISSUE: FDA notified healthcare professionals and patients that drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together.

A drug interaction study showed that taking boceprevir (Victrelis) with ritonavir (Norvir) in combination with atazanavir (Reyataz) or darunavir (Prezista), or with Kaletra (lopinavir/ritonavir) reduced the blood levels of the HIV medicines and boceprevir in the body (see Data Summary below). FDA will be updating the Victrelis drug label to include information about these drug interactions.

BACKGROUND: Victrelis is a hepatitis C virus (HCV) protease inhibitor used with the medicines peginterferon alfa and ribavirin to treat chronic (long-lasting) hepatitis C infection in adults. HIV protease inhibitors are a class of anti-viral drugs used to treat HIV infection. Ritonavir is an HIV protease inhibitor used to “boost” other HIV protease inhibitors, increasing their levels in the blood and making them more effective.

RECOMMENDATION: Patients should not stop taking any of their medicines without talking to their healthcare professional. Patients should contact their healthcare professional if they have any questions or concerns.

Healthcare professionals who have started patients infected with both chronic HCV and HIV on Victrelis and antiretroviral therapy containing a ritonavir-boosted protease inhibitor should closely monitor patients for HCV treatment response and for potential HCV and HIV virologic rebound.

Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm291144.htm

Montelukast fuera de indicacion en preescolares ?

2012-02-08T03:40:00.000-08:00

¿Montelukast fuera de indicación en preescolares?

Fuente: Hemos Leido

Publicado por MGG

Gracias a la cuenta de Twitter de Evidencias en Pediatría (@evidpediatria), recordábamos nuestro post sobre elmontelukast y su uso el bronquiolitis, que vimos pinchado en más de un corcho de nuestros centros de salud. Y uno se pregunta… ¿se usa montelukast fuera de indicación?
En nuestro ámbito sanitario no hemos encontrado datos publicados al respecto, pero hemos leído los resultados de un ensayo clínico publicado recientemente en Pediatrics, en donde se evaluó si el tratamiento profiláctico con montelukast 4 mg/día vs placebo durante 12 semanas, reducía laincidencia y la severidad de infecciones del tracto respiratorio superior, en niños sanos de edad preescolar (de entre 1 y 5 años de edad).
Este ensayo, realizado en Israel sobre 300 niños reclutados en 3 consultas pediátricas de atención ambulatoria, no mostró que redujera la incidencia de infecciones respiratorias del tracto superior, así como tampoco encontró diferencias en ninguna de las variables secundarias entre los dos grupos.
Revisando este tema nos preguntamos… ¿cómo habrá quedado el plan de gestión riesgos sobre el montelukast en pediatría, que se anunciaba en la sección 3 (Información sobre seguridad) del informe mensual de la AGEMED de febrero 2011 bajo el título Montelukast: notificación de casos de reacciones psiquiátricas?
El resumen de esa información decía: “se han notificado casos de alteraciones psiquiátricas y del comportamiento en pacientes tratados con montelukast. La revisión de los datos disponibles ha concluido que esta información está adecuadamente descrita en las fichas técnicas de los medicamentos que contienen montelukast. Adicionalmente se ha iniciado un plan de gestión de riesgos sobre el uso de montelukast en pediatría.”

Books: Patient Safety

2012-02-04T10:01:00.000-08:00

Patient Safety

Patient SafetyEdited by Juan A. Sanchez
February 2012
Volume 92
Issue 1

Content
http://www.sciencedirect.com/science/issue/273318-1-s2.0-S0039610911X00075
Copy to Clipboard
Link

http://www.mediafire.com/?kpuabc9gbdoi0jw

Australian Prescriber New Issue

2012-02-01T06:11:00.000-08:00

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http://www.australianprescriber.com/upload/pdf/issues/163.pd

From the editor...

This issue introduces the new look Australian Prescriber. The first issue of the new design is filled with interesting information.

We begin with Rob Moulds and Brendan Shaw giving their opinions on the decision to defer the inclusion of some new drugs on the Pharmaceutical Benefits Scheme.

The Pharmaceutical Benefits Scheme provides doctors with a range of drugs for use in an emergency. A table of suggested doses appears in this issue, but are some of the drugs still appropriate for practice in the 21st century? John Holmes assesses the emergency drugs and proposes some changes to the contents of the doctor's bag.

Opioids are not only used in emergencies, but are also prescribed for chronic pain. As there has been an increased use of opioids for non-cancer pain, Michael McDonough advises on how to reduce the dangers of this treatment.

Dangerous drugs need not be prescription medicines. Medicines Safety Update warns us about the hazards of some of the products available from the internet. Patients may not mention that they are using a product such as a complementary medicine. Margaret Duguid reminds us to ask patients about all the medicines they are taking. This is an important part of the process of medication reconciliation which aims to reduce medication errors.

Benjamin Davies is also concerned about drugs and other substances available online. Some substances can be difficult to detect in the laboratory.

Laboratory testing has a role in identifying the cause of fever in travellers. However, Anthony Gherardin and Jennifer Sisson emphasise the continuing importance of a thorough history and examination.

Contents

Deferring PBAC decisions: rationing as a reality (editorial)
Deferring PBAC decisions: industry view (editorial)
Time to restock the doctor's bag
The importance of medication reconciliation for patients and practitioners
Safe prescribing of opioids for persistent non-cancer pain Dangerous drugs online
Assessing fever in the returned traveller

Plus features
Emergency drug doses - PBS Doctor's bag items
Medicines Safety Update

Pneumovax 23 - updated revaccination recommendations
Caveat emptor ‘buyer beware’ - the risks of purchasing unregistered medicines online
Citalopram and QT prolongation - important changes to the dosing recommendations
Atomoxetine (Strattera) - risk of increased blood pressure and/or heart rate

Letters to the editor
Book review: Introduction to pharmaceutical calculations
Book review: Therapeutic Guidelines: Neurology
New drug review - Prucalopride for constipation

2012-01-23T05:21:00.000-08:00

Tysabri (natalizumab): Drug Safety Communication - New Risk Factor for Progressive Multifocal Leukoencephalopathy (PML)

AUDIENCE: Neurology, Gastroenterology

ISSUE: FDA notified healthcare profesisonals that testing positive for anti-JC virus (JCV) antibodies has been identified as a risk factor for progressive multifocal leukoencephalopathy (PML). PML is a rare but serious brain infection associated with use of Tysabri (natalizumab) for the treatment of multiple sclerosis (MS) or Crohn's disease.

A patient's anti-JCV antibody status may be determined using an anti-JCV antibody detection test that has been analytically and clinically validated, and has been ordered by a healthcare professional. The Stratify JCV Antibody ELISA test2 was cleared by FDA on January 20, 2012. Testing positive for anti-JCV antibodies means that a person has been exposed to JCV in the past.

BACKGROUND: Tysabri (natalizumab) is in a class of medications called immunomodulators. It works by stopping certain cells of the immune system from causing damage to the body. Tysabri is approved for the treatment of relapsing forms of multiple sclerosis since November 2004 and for the treatment of moderately to severely active Crohn's disease since January 2008.

RECOMMENDATION: The risks and benefits of continuing treatment with Tysabri should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more of the other known risk factors for PML. Patients with all three known risk factors have an estimated risk of PML of 11/1,000 users. See the Drug Safety Communication Data Summary section for additional information.

Informaciòn Agencia Española de Medicamentos

2012-01-20T07:45:00.000-08:00

Información sobre seguridad

El texto completo de las notas informativas está disponible en www.aemps.gob.es.

Aliskireno: inicio de la revaluación de su balance beneficio-riesgo

Después de la interrupción del ensayo clínico ALTITUDE, se ha iniciado la revaluación del balance beneficio-riesgo de aliskireno.

En espera de las conclusiones finales, la AEMPS recomienda como medida de precaución, no prescribir medicamentos con aliskireno a pacientes diabéticos en tratamiento simultáneo con inhibidores de la enzima convertidora de la angiotensina o con antagonistas de receptores de angiotensina II, así como revisar en la próxima consulta médica a este tipo de pacientes en tratamiento, utilizando otra alternativa terapéutica diferente a aliskireno.

Resumen de la nota informativa:
“ ALISKIRENO (RASILEZ®, RIPRAZO®, RASILEZ HTC®):
REVALUACIÓN DEL BALANCE BENEFICIO-RIESGO”
Nota informativa MUH (FV), 28 /2011

El Comité de Medicamentos de Uso Humano (CHMP), comité científico de la Agencia Europea de Medicamentos constituido por representantes de todas las agencias nacionales europeas, ha iniciado la revaluación del balance beneficio-riesgo de aliskireno tras ser informado de la interrupción del ensayo clínico ALTITUDE.

La interrupción de este ensayo clínico, que incluía pacientes diabéticos hipertensos, ha sido realizada por recomendación del comité independiente de seguimiento del estudio, debido a que los resultados disponibles no mostraban un beneficio clínico para los pacientes tratados con aliskireno, mientras que se observaron mas casos de ictus, complicaciones renales, hiperpotasemia e hipotensión en los pacientes que recibieron aliskireno, en comparación con los que recibieron placebo.

En espera del resultado final de la revaluación, la AEMPS, como medida de precaución, recomienda lo siguiente:

No prescribir medicamentos con aliskireno a pacientes diabéticos en tratamiento con IECA o ARAII.
Revisar el tratamiento de los pacientes que utilizan aliskireno en la próxima visita rutinaria de seguimiento del paciente, suspendiendo el tratamiento con aliskireno en el caso de pacientes diabéticos en tratamiento con IECA o ARAII.
Los pacientes no deben suspender el tratamiento con aliskireno sin consultar con su médico, ya que esto podría provocar un empeoramiento de su situación clínica.
Los pacientes que se encuentren participando en algún ensayo clínico, deben contactar con el médico que les atiende en el mismo para obtener información sobre la pauta a seguir con su tratamiento.

Análogos de la hormona liberadora de gonadotropina (GnRH) y riesgo de depresión

Algunos datos sugieren que el uso de análogos de GnRH se asocia con un incremento de riesgo de depresión, la cual puede ser grave. Se actualizarán las fichas técnicas y prospectos de estos medicamentos en Europa.

Tras el informe de un estudio en Japón en el que describían casos de depresión, incluyendo suicidio, en mujeres con endometriosis tratadas con análogos de GnRH¹, el titular de la autorización de comercialización de leuprorelina llevó a cabo un estudio epidemiológico con la base de datos GPRD (General Practitioner Research Database). Este estudio mostró un incremento de riesgo de nuevos casos de depresión en pacientes de endometriosis y cáncer de próstata y un incremento de riesgo de comportamiento suicida en pacientes de cáncer de próstata tratados con análogos de GnRH.

Por este motivo, las agencias de medicamentos nacionales de la Unión Europea decidieron evaluar detalladamente la nueva evidencia disponible a este respecto, teniendo en cuenta el riesgo de este tipo de alteraciones en los pacientes con cáncer de próstata u otras alteraciones que constituyen las indicaciones de los análogos de GnRH. Por otra parte, es conocido que los pacientes de cáncer de próstata tratados con análogos de GnRH tienen mayor riesgo de desarrollar depresión o de empeoramiento de una depresión preexistente. Además, también existe un riesgo potencial de cambios de comportamiento y depresión en mujeres tratadas con análogos de GnRH para condiciones no neoplásicas hormono-dependientes.

Los principios activos incluidos en esta revisión han sido: buserelina, goserelina, histrelina, leuprorelina, nafarelina y triptorelina.

Los datos evaluados en esta revisión son los procedentes del estudio llevado a cabo con la base de datos GPRD y los de una evaluación previa de la seguridad de leuprorelina basada en datos publicados^2-11, así como los procedentes de notificación espontánea de sospechas de reacciones adversas.

Los resultados del estudio realizado con la base de datos GPRD mostraron una tasa de nuevos casos de depresión de 1 a 10 casos por 100 pacientes-año en hombres y mujeres tratados con análogos de GnRH.

En las pacientes con endometriosis tratadas con análogos de GnRH se observó un incremento de riesgo de aproximadamente el 50% (RR 1,46; IC 95%: 1,12-1,89), aunque el riesgo observado se solapa con el obtenido en pacientes no expuestas (RR 1,38; IC 95%: 1,29-1,48).

En este mismo estudio, para los pacientes con cáncer de próstata se obtuvo un RR de nuevos casos de depresión de 1,97 (IC 95%: 1,86-2,10), superior al incremento de riesgo asociado al cáncer de próstata en sí mismo (RR 1,45; IC 95%: 1,35-1,55). Se observó un incremento de riesgo de comportamiento suicida en estos pacientes tratados con análogos de GnRH, aunque el número reducido de casos y el carácter retrospectivo y observacional de este estudio, hacen que estos resultados deban interpretarse con cautela.

La revisión de los artículos publicados^2-12 y de los casos procedentes de notificación espontánea muestran que la depresión y los cambios de comportamiento son riesgos conocidos relacionados con la reducción de los niveles de estrógenos/testosterona durante el tratamiento con análogos de GnRH.

La conclusión de esta revisión ha sido que el riesgo de depresión y cambios de comportamiento debe incluirse de forma consistente en las fichas técnicas de estos medicamentos. Las fichas técnicas y prospectos se actualizarán para incluir advertencias sobre el riesgo de depresión, que puede ser grave, así como sobre la necesidad de informar al paciente y establecer el tratamiento oportuno en caso necesario. Los cambios de comportamiento y depresión se incluirán en la sección de reacciones adversas.

Referencias:

Japan Endometriosis Association publishes third national study. April 2007; available under: http://endometriosis.org/news/support-awareness/japan-endometriosis-association-announces-significantly-adverse-effects-of-gnrh-use/
Cherrier MM, Aubin S, Higano CS. Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer. Psychooncology. 2009; 18: 237-247.
Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of the "androgen deprivation syndrome" in men receiving androgen deprivation for prostate cancer. Arch Intern Med. 2006; 166: 465-471.
Schmidt PJ, Berlin KL, Danaceau MA, Neeren A, Haq NA, Roca CA, Rubinow DR. The effects of pharmacologically induced hypogonadism on mood in healthy men. Arch Gen Psychiatry. 2004; 61: 997-1004.
Rosenblatt DE, Mellow A. Depression during hormonal treatment of prostate cancer. J Am Board Fam Pract. 1995; 8: 317-320.
Sepulcri Rde P, do Amaral VF. Depressive symptoms, anxiety, and quality of life in women with pelvic endometriosis. Eur J Obstet Gynecol Reprod Biol. 2009; 142: 53-56.
Steingold KA, Cedars M, Lu JK, Randle D, Judd HL, Meldrum DR. Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist. Obstet Gynecol. 1987; 69: 403-411.
Warnock JK, Bundren JC. Anxiety and mood disorders associated with gonadotropin-releasing hormone agonist therapy. Psychopharmacol Bull. 1997; 33: 311-316.
Bloch M, Azem F, Aharonov I, Ben Avi I, Yagil Y, Schreiber S, Amit A, Weizman A. GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization-embryo transfer cycles. Fertil Steril. 2011; 95: 307-309.
Friedman AJ, Hoffman DI, Comite F, Browneller RW, Miller JD. Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. Obstet Gynecol. 1991; 77: 720-725.
Toren P, Dor J, Mester R, Mozes T, Blumensohn R, Rehavi M, Weizman A. Depression in women treated with a gonadotropin-releasing hormone agonist. Biol Psychiatry. 1996; 39: 378-82.

Inhibidores de la bomba de protones (IBP) y riesgo de hipomagnesemia

Se han identificado casos de hipomagnesemia asociados al uso prolongado de IBP.

Se recomienda a los profesionales sanitarios tener presente esta reacción adversa que, aunque poco frecuente, puede resultar potencialmente grave y considerar llevar a cabo determinaciones plasmáticas de magnesio a aquellos pacientes con tratamientos prolongados con IBP o que los estén tomando junto con otro medicamento que pueda producir hipomagnesemia.

Resumen de la nota informativa:
“ RIESGO DE HIPOMAGNESEMIA ASOCIADO A LOS MEDICAMENTOS INHIBIDORES DE LA BOMBA DE PROTONES (IBP)”
Nota informativa MUH (FV), 27 /2011

La AEMPS ha informado del riesgo de hipomagnesemia asociado al uso de IBP. Después de generarse una señal de farmacovigilancia, las agencias nacionales de medicamentos de la Unión Europea han revisado la información disponible a este respecto (datos procedentes de la bibliografía, casos procedentes de notificación espontánea de sospechas de reacciones adversas y otras fuentes de información).

El análisis de la información disponible refleja la notificación de casos de hipomagnesemia para distintos IBP. Teniendo en cuenta además los distintos mecanismos de acción propuestos para esta reacción adversa, se ha considerado que este es un efecto de clase de los IBP.

Una característica importante de muchos de los pacientes afectados es que presentaron signos de hipomagnesemia durante meses o años y tuvieron que ser ingresados en el hospital en varias ocasiones antes de que se sospechara que el cuadro clínico que presentaban podía estar relacionado con el tratamiento con IBP.

Un aspecto de interés acerca de esta reacción adversa es que se ha observado en pacientes que llevan tomando el medicamento al menos 3 meses, y en la mayoría de los casos 1 año. Así, y aun considerando que esta reacción sería muy poco frecuente (aunque la frecuencia no está bien establecida), debe considerarse el amplio uso de estos medicamentos en la población y la necesidad de realizar un diagnóstico correcto de estos casos.

La Agencia Española de Medicamentos y Productos Sanitarios ha recomendado a los profesionales sanitarios lo siguiente:

Valorar la posibilidad diagnóstica de hipomagnesemia ante la aparición de sintomatología compatible no explicada en pacientes en tratamientos prolongados con IBP.
Considerar la posibilidad de realizar determinaciones plasmáticas de magnesio (previo al inicio y periódicamente durante el tratamiento) a aquellos pacientes:
- Sometidos a tratamientos prolongados con IBP.
- Que estén tomando IBP junto con digoxina o cualquier otro medicamento con capacidad para reducir los niveles plasmáticos de magnesio (ej.: diuréticos).

Inhibidores de la HMG-CoA reductasa (estatinas) y riesgo de diabetes

Los inhibidores de la HMG-CoA reductasa (estatinas) pueden incrementar el riesgo de aparición de diabetes mellitus en pacientes con riesgo de desarrollar la enfermedad. Es necesario monitorizar a estos pacientes. El balance beneficio-riesgo de las estatinas se mantiene claramente favorable.

Después de la publicación de un metaanálisis¹ en el que se observó que el tratamiento con estatinas se asociaba con un ligero incremento de la aparición de diabetes mellitus (DM), las agencias de medicamentos nacionales de la Unión Europea han llevado a cabo una evaluación de este riesgo, basada en todos los datos disponibles.

Diversos ensayos clínicos han analizado el riesgo de aparición de DM asociado al uso de estatinas con cierta inconsistencia en los resultados. Mientras algunos estudios mostraban una reducción de riesgo², otros sugerían un incremento del mismo^3-4. Un metanálisis de 13 ensayos clínicos¹obtuvo resultados que mostraban un ligero incremento de riesgo (odds ratio 1.09; IC 95% 1.02-1.17), estimando sus autores la aparición de 1 caso adicional por cada 1.000 personas-año de tratamiento, lo que representa la aparición de 1 caso por cada 255 pacientes tratados durante 4 años.

Dado el amplio uso que tienen estos medicamentos, un ligero incremento de riesgo puede representar un número relevante adicional de casos de DM por año. Los principios activos incluidos en esta revisión han sido: atorvastatina, fluvastatina, pitavastatina, pravastatina, rosuvastatina y simvastatina. Para cada uno de estos principios activos se han revisado los estudios clínicos y no clínicos disponibles.

Obtener una conclusión general sobre las estatinas como grupo a través de los resultados de los ensayos clínicos disponibles está sujeto a diversas limitaciones ya que los diferentes estudios analizados presentan variabilidad en cuanto a la inclusión de diferentes tipos de pacientes, duración del estudio y dosis empleadas. Adicionalmente, en la mayoría de los estudios, el diagnóstico de diabetes no constituía un objetivo del estudio y, por tanto, el criterio diagnóstico es variable.

Del análisis de los estudios clínicos y no clínicos disponibles, se ha concluido que existe suficiente evidencia que apoya la relación causal entre el uso de estatinas y la aparición de DM. Sin embargo, este riesgo incrementado parece circunscribirse predominantemente a pacientes con riesgo de desarrollar DM. La glucemia en ayunas aumentada antes de iniciar el tratamiento se considera un factor clave en la identificación de la población en riesgo, otros factores de riesgo incluyen historia de hipertensión arterial, aumento de triglicéridos o incremento del índice de masa corporal (IMC).

Por otra parte, en todos los ensayos clínicos se mostró que el beneficio cardiovascular de las estatinas es de la misma magnitud en los pacientes que desarrollaron DM que en aquellos en los que no apareció. Aunque se ha estimado la aparición de 1 caso de DM por cada 255 pacientes tratados con estatinas durante 4 años, se considera que con esta misma exposición a estatinas se evitarían 5,4 muertes o infartos de miocardio, además del mismo número de accidentes cerebrovasculares o revascularizaciones coronarias. Por lo tanto, la proporción estimada es de 9 a 1 a favor del beneficio cardiovascular.

A pesar de que se ha concluido que el riesgo de desarrollar DM está incrementado en pacientes susceptibles, los estudios disponibles muestran claramente que el beneficio del uso de estatinas en la reducción de acontecimientos cardiovasculares mayores, se mantiene en este tipo de pacientes. Por lo tanto, el balance beneficio-riesgo de estos medicamentos se mantiene favorable, incluyendo aquellos pacientes con riesgo de aparición de DM o en aquellos con DM diagnosticada al inicio del tratamiento.

Las fichas técnicas y prospectos de los medicamentos con estatinas se actualizarán, incluyendo una advertencia indicando que los pacientes en riesgo de sufrir DM (glucemia en ayunas 5,6-6,9 mmol/L, IMC>30 kg/m², nivel de triglicéridos aumentado o hipertensión arterial), deben ser monitorizados, según las recomendaciones de las guías de práctica clínica. DM se incluirá como una reacción adversa frecuente en la sección correspondiente de las fichas técnicas y los prospectos.

Referencias:

Sattar N, Preiss D, Murray HM et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010; 375: 735-742.
Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, Gaw A. Pravastatin and the Development of Diabetes Mellitus: Evidence for a Protective Treatment Effect in the West of Scotland Coronary Prevention Study. Circulation. 2001; 103: 357-362.
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med. 2008; 359: 2195-2207.
Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002; 360: 1623-1630.
(Pueden consultarse las referencias de los estudios revisados en el informe mensual de diciembre de 2011 del Pharmacovigilance Working Party)

Somatropina: se confirma el balance beneficio-riesgo favorable

Tras la evaluación europea llevada a cabo, se confirma que la relación beneficio-riesgo de los medicamentos que contienen somatropina permanece favorable para las indicaciones terapéuticas y dosis autorizadas.

Somatropina no debe administrarse si existe evidencia de actividad tumoral y no deben excederse las dosis máximas establecidas.

Resumen de la nota informativa:>
“ LA EVALUACIÓN EUROPEA DE LA SOMATROPINA CONFIRMA LA RELACIÓN BENEFICIO-RIESGO FAVORABLE EN LAS CONDICIONES DE USO AUTORIZADAS”
Nota informativa MUH (FV), 26 /2011

La AEMPS ha informado a los profesionales sanitarios sobre las conclusiones de la revisión del balance beneficio-riesgo de somatropina (ver tambiénnota informativa de la AEMPS 17/2010). Para dicha revisión se han evaluado todos los datos disponibles sobre somatropina, procedentes de ensayos clínicos, registros y estudios observacionales y notificaciones espontáneas de sospechas de reacciones adversas.

Dicha revisión se inició en diciembre de 2010, tras conocerse los resultados preliminares de un estudio epidemiológico realizado en Francia que sugerían que los pacientes adultos que habían sido tratados con somatropina durante la infancia presentaban un riesgo de mortalidad superior al de la población general.

Sin embargo, tras la evaluación llevada a cabo, se ha concluido que el estudio francés adolece de diversas limitaciones metodológicas y que sus resultados no son consistentes. Por otra parte, se ha observado que el resto de la información y estudios disponibles no corroboran que pueda existir un incremento de mortalidad tras el uso de somatropina, por lo que considera que el balance-beneficio riesgo de somatropina se mantiene favorable en sus indicaciones autorizadas.

La AEMPS recuerda a los profesionales sanitarios lo siguiente:

El balance beneficio-riesgo de los medicamentos que contienen somatropina permanece favorable para las indicaciones terapéuticas y las dosis actualmente establecidas.
No debe administrarse somatropina si existe evidencia de actividad tumoral.
No deben excederse las dosis máximas establecidas.

Canadian Adverse Reaccion Newsletter

2012-01-11T09:36:00.000-08:00

Image via WikipediaEsta en linea el Canadian Adverse Reaction Newsletter, Volume 22, No.
1* , correspondiente a enero 2012

Indice:

* Second-generation antipsychotics and cardiometabolic adverse
reactions in children and adolescents
* Prescription drugs and pediatric patients
* Canadian Paediatric Surveillance Program
* Adverse reaction reporting in children: update
* Adverse reaction reporting form
* Did you know? The Drug Safety and Effectiveness Network (DSEN) and
pediatric projects
* Summary of advisories

Disponible* en:

http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/bulletin/carn-bcei_v22n1-eng.pdf

Saludos,

Martín

Martín Cañás
Gapurmed

Reacciones adversas a medicamentos y notificacion

2012-01-06T11:25:00.000-08:00

Las reacciones adversas a los medicamentos y su notificación

Jueves, Enero 5, 2012

Por admin

Ya hemos hablado de lo importante que es la farmacovigilancia y notificar las sospechas de reacciones adversas de los medicamentos, y hoy queremos profundizar un poco más en el tema.
¿Qué es una Reación Adversa?
Cualquier respuesta a un medicamento que sea nociva y no intencionada, y que tenga lugar a dosis que se apliquen normalmente en el ser humano para la profilaxis, el diagnóstico o el tratamiento de enfermedades, o para la restauración, corrección o modificación de funciones fisiológicas. Este término incluye también todas las consecuencias clínicas perjudiciales derivadas de la dependencia, abuso y uso incorrecto de medicamentos, incluyendo las causadas por el uso fuera de las condiciones autorizadas y las causadas por errores de medicación.
¿Cuándo se deben notificar las reacciones adversas?
Siempre que tengamos la sospecha de una posible relación causal de los signos y síntomas de una reacción adversa en el paciente con el uso de un medicamento. Algo aparente insignificante puede ayudar a identificar problemas de seguridad en los medicamentos. Además hay que notificar aunque nos falte algún dato.
¿Cómo se notifican las RAM?
Utilizando las “tarjetas amarillas”, con franqueo en destino, que ponen a su disposición los correspondientes Centros Autonómicos de Farmacovigilancia o comunicándolo al Laboratorio farmacéutico titular del medicamento relacionado, cuyo Responsable de Farmacovigilancia debe reunir la información del caso, antes de notificarlo al SEFV-H.
Quien quiera más información al respecto se puede descargar el documento emitido por el Ministerio de Sanidad

Informaciòn Agencia Española de Medicamentos

2011-12-18T08:49:00.000-08:00

Atomoxetina y aumento de la presión arterial y frecuencia cardíaca. Nuevas recomendaciones

La revisión de los datos procedentes de ensayos clínicos ha mostrado que atomoxetina puede producir cambios clínicamente importantes en la presión arterial y en la frecuencia cardíaca. Atomoxetina está contraindicada en pacientes con enfermedad cardiovascular o cerebrovascular graves. Antes de iniciar el tratamiento debe evaluarse la presencia o antecedentes de patología cardiaca. Se debe llevar a cabo una monitorización de la presión arterial y de la frecuencia cardíaca durante el tratamiento.

Resumen de la nota informativa:
"ATOMOXETINA (STRATTERA®) Y AUMENTO DE LA PRESIÓN ARTERIAL Y FRECUENCIA CARDÍACA: NUEVAS RECOMENDACIONES"
Nota informativa MUH (FV), 25 /2011

Un análisis reciente de los datos combinados de ensayos clínicos controlados y no controlados con atomoxetina en niños y adultos, ha mostrado que una proporción de pacientes tratados con atomoxetina (aproximadamente 6-12% de niños y adultos) experimentaron cambios clínicamente relevantes en la frecuencia cardíaca (20 lpm o más) o en la presión arterial (15-20 mm Hg o más).

Adicionalmente, en un número reducido (15-32%) de los pacientes que experimentaron cambios clínicamente relevantes en la presión arterial y frecuencia cardíaca, éstos se mantuvieron en el tiempo o progresaron.

No es posible identificar factores de riesgo o grupos específicos de pacientes de especial riesgo, por lo que se considera necesario una evaluación clínica y cardiovascular antes y durante el tratamiento con atomoxetina, especialmente en aquellos pacientes que pueden ser susceptibles de un empeoramiento de su situación clínica por este motivo.

La AEMPS, ha establecido las siguientes recomendaciones para los profesionales sanitarios:

El uso de atomoxetina está contraindicado en pacientes con trastornos cardiovasculares o cerebrovasculares graves en los que se puede esperar un deterioro con un incremento en la presión arterial o en la frecuencia cardiaca clínicamente importante.
En aquellos pacientes en los que se esté considerando el tratamiento, se recomienda realizar un minucioso examen físico e historia clínica para evaluar la presencia de enfermedad cardíaca.
Atomoxetina debe utilizarse con precaución en pacientes que pudiesen empeorar por un aumento de la presión arterial o de la frecuencia cardiaca, tales como pacientes con hipertensión, taquicardia, o enfermedades cardiovasculares o cerebrovasculares.

La frecuencia cardíaca y la presión arterial se deben medir y registrar en todos los pacientes antes de que comiencen el tratamiento con atomoxetina, así como después de cada ajuste de dosis y al menos cada 6 meses durante el tratamiento. Si el paciente desarrolla síntomas que sugieran un trastorno cardíaco durante el tratamiento, debe ser remitido a un cardiólogo para una evaluación inmediata.

Domperidona y riesgo cardíaco

Algunos estudios epidemiológicos muestran que domperidona puede asociarse con un aumento de riesgo de arritmias ventriculares graves o muerte súbita de origen cardíaco. Este riesgo parece ser superior en pacientes mayores de 60 años o en aquellos que toman dosis diarias superiores a 30 mg. Debe utilizase la menor dosis eficaz posible, tanto en adultos como en niños.

Resumen de la nota informativa:
"DOMPERIDONA Y RIESGO CARDÍACO"
Nota informativa MUH (FV), 24 /2011

Las agencias nacionales de medicamentos de la Unión Europea han revisado la información disponible relativa a la seguridad cardíaca de domperidona, en particular la procedente de los estudios epidemiológicos disponibles y los datos de notificación espontánea de sospechas de reacciones adversas.

La conclusión de esta evaluación indica que domperidona puede estar asociada con un ligero aumento del riesgo de sufrir arritmias ventriculares graves o muerte súbita de origen cardíaco, en particular en pacientes mayores de 60 años o en pacientes que utilizan una dosis diaria mayor de 30 mg. El balance beneficio-riesgo de domperidona en sus indicaciones autorizadas se mantiene favorable.

De acuerdo con estas conclusiones, la AEMPS ha recomendado a los profesionales sanitarios:

Valorar si el paciente tiene antecedentes de patología cardíaca a la hora de prescribir domperidona, teniendo especial precaución en pacientes con antecedentes de prolongación de intervalos de la conducción cardiaca, particularmente QTc, con trastornos electrolíticos significativos o enfermedades cardíacas subyacentes como insuficiencia cardiaca congestiva.
Utilizar la menor dosis eficaz posible, tanto en adultos como en niños.
Tener especial precaución en el uso de domperidona en pacientes de edad avanzada o en aquellos que utilizan dosis altas de domperidona.

Escitalopram: riesgo de prolongación del intervalo QT del electrocardiograma

Escitalopram puede producir una prolongación dosis dependiente del intervalo QT del electrocardiograma. Por ello, la dosis máxima recomendada de escitalopram en pacientes mayores de 65 años se reduce a 10mg al día.

Resumen de la nota informativa:
"ESCITALOPRAM: PROLONGACIÓN DEL INTERVALO QT DEL ELECTROCARDIOGRAMA"
Nota informativa MUH (FV), 23 /2011

Una vez finalizada la evaluación de citalopram y su relación con la prolongación del intervalo QT del electrocardiograma (ECG) (ver nota informativa 19/2011 de la AEMPS ), se ha revisado la información disponible a este respecto para escitalopram, enantiómero de citalopram con indicaciones similares.

En base a los resultados de la evaluación realizada, la AEMPS ha informado a los profesionales sanitarios de lo siguiente:

Debido al riesgo de prolongación del intervalo QT del ECG a dosis altas, en pacientes mayores de 65 años, la dosis máxima recomendada de escitalopram pasa a ser de 10 mg al día.
Se contraindica el uso de escitalopram en las siguientes situaciones:
- Pacientes con antecedentes de intervalo QT alargado o síndrome congénito del segmento QT largo.
- Uso concomitante con medicamentos con capacidad para prolongar el intervalo QT del electrocardiograma.
Escitalopram se debe utilizar con precaución en pacientes en los que coexistan otros factores de riesgo de desarrollar Torsade de Pointes, por ejemplo aquellos con insuficiencia cardiaca congestiva descompensada, infarto de miocardio, bradiarritmias o predisposición a hipopotasemia o hipomagnesemia por enfermedad o medicación concomitante.

La AEMPS ha establecido las siguientes recomendaciones:

Los médicos deberán reevaluar a los pacientes mayores de 65 años tratados con una dosis superior a la que acaba de ser establecida, e iniciar la reducción de la misma de modo gradual con el objeto de evitar la aparición de síntomas de retirada.
Se debe informar a los pacientes para que:
- Contacten con su médico inmediatamente, si durante el tratamiento con escitalopram experimentan signos y/o síntomas relacionados con alteración de la frecuencia o el ritmo cardiaco.
- No interrumpan, modifiquen o reduzcan la dosis de escitalopram por su cuenta, sin consultar previamente a un médico.

Espironolactona: riesgo de hiperpotasemia

La AEMPS recuerda a los profesionales sanitarios que para prevenir la aparición de hiperpotasemia durante el tratamiento de la insuficiencia cardiaca congestiva (ICC) con espironolactona, se deben utilizar las dosis recomendadas para esta indicación (25 a 50 mg/día) y llevar a cabo determinaciones periódicas de los niveles séricos de potasio.

Resumen de la nota informativa:
"ESPIRONOLACTONA Y RIESGO DE HIPERPOTASEMIA"
Nota informativa MUH (FV), 22 /2011

El Sistema Español de Farmacovigilancia de medicamentos de uso humano ha seguido recibiendo notificaciones de casos de hiperpotasemia asociados al uso de espironolactona. En algunos casos, los pacientes recibían dosis inadecuadas (100 a 300 mg diarios) de espironolactona, o junto con más de un inhibidor de la enzima conversora de angiotensina (IECA) o con otros ahorradores de potasio, o incluso manteniendo suplementos de potasio.

Teniendo en cuenta la situación, la AEMPS ha recomendado a los profesionales sanitarios las siguientes medidas:

Es crítico vigilar y controlar los niveles séricos de potasio en pacientes con insuficiencia cardiaca clases III y IV de la NYHA que reciben espironolactona.
La dosis para el tratamiento de la ICC no debe ser superior a 50 mg diarios. Por tanto, las presentaciones de 100 mg de espironolactona por comprimido no deben utilizarse en estos pacientes.
Debe evitarse el uso concomitante con otros diuréticos ahorradores de potasio (amilorida, triamtereno) o antagonistas de la aldosterona (eplerenona, drospirenona).
Debe evitarse el uso de suplementos de potasio orales en pacientes con niveles séricos de potasio > 3,5 mmol/L.
Debe recordarse que el uso simultáneo con IECA, ARA-II, beta-bloqueantes, heparinas, AINE y sal de mesa para hipertensos facilita la aparición de hiperpotasemia .
Los controles de potasio y creatinina séricos deben realizarse en la semana siguiente al inicio del tratamiento o cuando se aumente la dosis de espironolactona, posteriormente cada mes durante los 3 primeros meses, luego cada trimestre durante un año y tras el año de tratamiento, cada seis meses.
En pacientes de más de 80 años debe valorarse la filtración glomerular y una posible insuficiencia renal oculta.
Interrumpir transitoria o definitivamente el tratamiento si los niveles séricos de potasio son > 5 mmol/L o de creatinina son >4 mg/dL.

Rosuvastatina: riesgo de ginecomastia

No se puede descartar la asociación del uso de rosuvastatina y ginecomastia, teniendo en cuenta la información procedente de ensayos clínicos, notificación espontánea de sospechas de reacciones adversas y de los casos publicados en la literatura. Se incorporará ginecomastia como posible reacción adversa de frecuencia muy rara en las fichas técnicas de los medicamento con rosuvastatina.

Tras la identificación de una señal de farmacovigilancia de ginecomastia con rosuvastatina, las agencias de medicamentos nacionales de la Unión Europea, han revisado la información aportada por el laboratorio titular de la autorización de comercialización, procedente de ensayos clínicos, notificación espontánea de sospechas de reacciones adversas y de casos publicados en la literatura. Por otra parte, ginecomastia se ha identificado como posible reacción adversa de atorvastatina.

Se han comunicado diversos casos en estas fuentes de información. En un ensayo clínico frente a placebo, la frecuencia de casos de ginecomastia fue superior en el grupo tratado con rosuvastatina que en el grupo que recibió placebo (1,6% vs. 1,1%). También se han comunicado algunos casos en la bibliografía y por notificación espontánea de sospechas de reacciones adversas.

Entre los casos notificados después de la comercialización, en algunos de ellos se observó la resolución del problema después de la retirada del fármaco, en un caso se notificó la reexposición positiva con la aparición de ginecomastia de nuevo tras la retirada y posterior reintroducción del tratamiento con rosuvastatina.

Tomando como base esta información, se ha concluido que la asociación de rosuvastatina y ginecomastia no se puede descartar. Rosuvastatina podría contribuir a la aparición de ginecomastia en pacientes susceptibles para ello (p. ej. pacientes obesos o de edad avanzada).

Se incorporará ginecomastia como posible reacción adversa en la ficha técnica de los medicamentos con rosuvastatina, con una frecuencia de aparición muy rara.

Tibolona: riesgo de tromboembolismo venoso, infarto de miocardio, cáncer de mama y cáncer de ovario

Se va a actualizar la información de la ficha técnica y prospecto de los medicamentos compuestos por tibolona con el fin de incorporar la nueva información disponible sobre el riesgo de tromboembolismo venoso (TEV), infarto de miocardio, cáncer de mama y cáncer de ovario.

Tibolona es una hormona sintética con propiedades estrogénicas, progesterónicas y androgénicas que en España se encuentra autorizada, a dosis de 2,5 mg, para el tratamiento de los síntomas de deficiencia de estrógenos en mujeres postmenopáusicas (más de 1 año). En algunos otros estados miembros de la Unión Europea, tibolona se encuentra autorizada además, para prevención de la osteoporosis en mujeres postmenopáusicas con riesgo de padecer fracturas y que no toleran o bien tienen contraindicado el uso de otros medicamentos para el tratamiento de la osteoporosis.

Durante el proceso de evaluación que se ha llevado a cabo, el riesgo de tromboembolismo venoso (TVE) fue valorado conjuntamente a partir de las notificaciones espontáneas de sospechas de reacciones adversas que se habían recibido, de los datos procedentes de ensayos clínicos y de un estudio de casos y controles realizado sobre la base de datos inglesa GPRD¹ diseñado para investigar el efecto de tibolona y otras terapias hormonales sobre la incidencia del TVE. Los resultados de este último estudio muestran que el riesgo de TVE asociado al uso de tibolona es inferior al que se asocia a la terapia hormonal sustitutiva convencional. En cualquier caso, estos datos son tan limitados que no permiten excluir la existencia de un pequeño riesgo de TVE entre los pacientes que toman tibolona en comparación con los pacientes que no toman este medicamento.

El riesgo de infarto agudo de miocardio se evaluó a partir de otro estudio epidemiológico llevado a cabo con la misma base de datos². En este caso, el número de pacientes que se encontraban en tratamiento con tibolona era demasiado pequeño como para poder detectar diferencias con respecto al grupo de pacientes no tratados. Aunque los datos resultan insuficientes para calcular la magnitud exacta del posible riesgo, sugieren que tibolona no protege a las mujeres postmenopáusicas frente al infarto agudo de miocardio.

El riesgo de cáncer de mama y ovario, fue evaluado a partir del estudio denominado The Million Women³, a partir del cual se concluyó que el riesgo relativo de cáncer de ovario asociado al uso de tibolona resulta similar al que se asocia con otros tipos de tratamiento hormonal sustitutivo.

Se incluirá información detallada sobre todos estos aspectos en las fichas técnicas y prospectos de los medicamentos que contienen tibolona. El re-análisis de los datos de otro de los estudios evaluados⁴ no justifica sin embargo modificar la información que actualmente figura sobre el riesgo de accidente cerebro-vascular y que se encuentra basada en el estudio LIFT⁵.

Referencias

Renoux C, Dell'Aniello S, Suissa S. Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. J Thromb Haemost. 2010; 8: 979-986.
de Vries CS, Bromley SE, Farmer RDT. Myocardial infarction risk and hormone replacement: differences between products. Maturitas. 2006; 53: 343-350.
Million Women Study Collaborators, eds. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003; 362: 419-427.
Rossouw, JE, Prentice RL, Manson JE, Wu LL, Barad D, Barnabei VM, Ko M, LaCroix AZ, Margolis KL, Stefanick ML. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. J Am Med Assoc. 2007; 297: 1465-1477.
Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, Mol-Arts M, Kloosterboer L, Mosca L, Christiansen C, Bilezikian J, Kerzberg EM, Johnson S, Zanchetta J, Grobbee DE, Seifert W, Eastell R; LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008; 359: 697-708.

Topiramato y riesgo de malformaciones congénitas

Como resultado de la nueva evaluación que se ha llevado a cabo sobre este asunto, se va a actualizar la ficha técnica y prospecto de todos los medicamentos que contienen topiramato. Se incluirá información relativa al incremento del riesgo de aparición de malformaciones congénitas si se administra durante el embarazo.

Se han evaluado los datos procedentes de dos registros (uno inglés y otro americano¹) puestos en marcha para valorar el uso de los medicamentos antiepilépticos durante el embarazo. En ambos registros aparecen casos de malformaciones graves en recién nacidos de madres que fueron tratadas, tanto en monoterapia como en combinación, con topiramato. Aunque el número de casos observados aún es relativamente pequeño, los datos continúan mostrando un incremento de riesgo. La información no clínica también muestra claramente este potencial teratogénico.

En consecuencia, se va a proceder a actualizar con esta nueva información, la ficha técnica y el prospecto de todos los medicamentos que contienen topiramato. Se hará constar, que los niños expuestos durante el primer trimestre del embarazo a un tratamiento en monoterapia con este medicamento, presentan un mayor riesgo de sufrir malformaciones congénitas, por ejemplo: defectos craneofaciales como paladar hendido y labio leporino; hipospadias; y defectos en los que se ven afectados diversos sistemas del organismo del recién nacido.

Topiramato está indicado:

En monoterapia en adultos, adolescentes y niños mayores de 6 años de edad con crisis epilépticas parciales con o sin crisis generalizadas secundarias, y crisis tónico-clónicas generalizadas primarias.
Como tratamiento concomitante en niños de 2 o más años de edad, adolescentes y adultos con crisis epilépticas parciales con o sin generalización secundaria o crisis tónico-clónicas generalizadas primarias y para el tratamiento de crisis asociadas con el Síndrome de Lennox-Gastaut.
En adultos, para el tratamiento profiláctico de la migraña, después de una cuidadosa evaluación de otras posibles alternativas terapéuticas. Topiramato no está indicado para el tratamiento agudo. Se encuentra contraindicado en la profilaxis de la migraña durante el embarazo y en las mujeres en riesgo de embarazo que no estén usando un método anticonceptivo eficaz.

Referencias

The North American Antiepileptic Pregnancy Registry (NAAED) y the UK Epilepsy and Pregnancy Register.

5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer

2011-12-14T19:22:00.000-08:00

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5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer

Drugs in the 5-ARI class include finasteride and dutasteride. These drugs are marketed under the brand-names Proscar, Propecia, Avodart, and Jalyn

[Posted 06/09/2011]

AUDIENCE: Urology, Family Medicine, Internal Medicine

ISSUE: FDA notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer).

BACKGROUND: The new safety information is based on FDA’s review of two large, randomized controlled trials––the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. Proscar, Avodart, and Jalyn are approved to improve symptoms of an enlarged prostate gland (benign prostatic hyperplasia or BPH). Proscar and Avodart are also approved to reduce the risk of urinary retention or surgery related to an enlarged prostate.Propecia is approved to treat male pattern hair loss.

RECOMMENDATION: Prior to initiating therapy with 5-ARIs, perform appropriate evaluation to rule out other urological conditions, including prostate cancer, that might mimic benign prostatic hyperplasia (BPH). See Drug Safety Communication for a Data Summary and additional information.

Healthcare professionals and patients are encouraged to report adverse events, side effects, or product quality problems related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[06/09/2011 - Drug Safety Communication - FDA]

[06/09/2011 - Q and A's - FDA]

Alertas de la AEMPS

2011-12-13T14:43:00.000-08:00

En las últimas semanas, desde el 27 de octubre, la Agencia Espanhola
de Medicamentos (Aemps) ha emitido las siguientes Notas:

-Nota informativa MUH (FV), 25 /2011: ATOMOXETINA (STRATTERA®) Y
AUMENTO DE LA PRESIÓN ARTERIAL Y FRECUENCIA CARDÍACA: NUEVAS
RECOMENDACIONES” (ver en
http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_25-2011.htm)

-Nota informativa MUH (FV), 24 /2011: “DOMPERIDONA Y RIESGO CARDIACO”
(ver en http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_24-2011.htm)

-Nota informativa MUH (FV), 23 /2011: “ESCITALOPRAM: PROLONGACIÓN DEL
INTERVALO QT DEL ELECTROCARDIOGRAMA” (ver en
http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_23-2011.htm)

-Nota informativa MUH (FV), 22 /2011: “ESPIRONOLACTONA Y RIESGO DE
HIPERPOTASEMIA” (ver en
http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_22-2011.htm)

-Nota informativa MUH (FV), 21 /2011: "DABIGATRÁN ( PRADAXA®) Y RIESGO
DE HEMORRAGIA: NUEVAS RECOMENDACIONES DE VIGILANCIA DE LA FUNCIÓN
RENAL" (ver en http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_21-2011.htm

-Nota informativa MUH (FV), 20 /2011: "METOCLOPRAMIDA: RESTRICCIONES
DE USO EN NIÑOS Y ADOLESCENTES" (ver en
http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_20-2011.htm)

-Nota informativa MUH (FV), 19 /2011: "CITALOPRAM Y PROLONGACIÓN DEL
INTERVALO QT DEL ELECTROCARDIOGRAMA" (ver en
http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2011/NI-MUH_19-2011.htm)

Éstas y otras informaciones de interés se publican cada mes de forma
agregada en los INFORMES MENSUALES, que se pueden acceder desde la
página http://www.aemps.gob.es/informa/informeMensual/home.htm

Un abrazo,

Mariano Madurga
Madrid, Espanha
mmadurgasanz@gmail.com
mmadurga@aemps.es
web: www.aemps.gob.es

Merck se declara culpable de publicidad engañosa

2011-11-24T17:55:00.000-08:00

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Merck se declara culpable de publicidad engañosa

BBC (Gran Bretaña) 22-11-11, EFE, 22-11-11 y Terra (col) 22-11-11

El gigante farmacéutico estadounidense, Merck, acordó este martes pagar una multa cercana a los US$1.000 millones y declararse culpable de haber publicitado de manera engañosa al analgésico Vioxx.
Vioxx fue presentado como un tratamiento para la artritis reumatoide antes de que fuese aprobado oficialmente.
El fármaco puesto a la venta en 1999, fue retirado del mercado en 2004, cuando se descubrió que aumentaba el riesgo de ataques cardíacos y accidentes cerebrovasculares. Según la FDA, fue responsable de entre 88.000 y 139.000 crisis cardiacas en cinco años, y entre 30% y 40% de las crisis cardiacas imputables al uso de Vioxx probablemente fueron mortales.

Merck, que se declaró culpable ante la justicia federal, pagará una multa penal de 321,64 millones de dólares por haber recomendado el uso de Vioxx a pacientes que sufren de artritis reumatoide, antes que esta utilización fuera autorizada por el organismo regulador FDA, indicó el Departamento de Justicia de Estados Unidos. 628,4 millones serán para resolver la demanda civil .
Según un comunicado la empresa subrayó que el pacto "no constituye admisión alguna de mala fe o responsabilidad".

"Toda actividad de marketing que ignora la importancia de una aprobación de la FDA, o que afirma hechos no establecidos sobre la seguridad de un medicamento, es inaceptable y será objeto de fuertes castigos tanto por la vía penal como por la civil", declaró la fiscal federal de Massachusetts (noreste), Carmen Ortiz, en un comunicado.

Merck había retirado de forma voluntaria el medicamento del lucrativo mercado mundial en 2004. Pero el laboratorio fue posteriormente objeto de múltiples demandas judiciales por parte de los afectados, ya que se estableció que los peligros del medicamento pudieron haber sido identificados cuatro años antes.

En 2007, el laboratorio había aceptado un acuerdo por 4.850 millones de dólares para saldar más del 95% de las 26.600 demandas entabladas contra Vioxx.

Martin Cañás
Fundación Femeba
La Plata
(Argentina)

2011-11-11T19:24:00.000-08:00

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The Lancet, Volume 378, Issue 9804, Page 1677, 12 November 2011

doi:10.1016/S0140-6736(11)61723-6 Cite or Link Using DOI

Non-medical use of painkillers in the USA

The Lancet

In the USA, pain is managed with pain relievers that include opioid analgesic drugs such as oxycodone, methadone, hydrocodone, and oxymorphone. With different types of opioid drugs available and frequently prescribed, these drugs have become increasingly prone to non-medical use. It is estimated that non-medical use of opioid drugs in the USA costs the health-care system US$72·5 billion each year. And in 2009, 500 000 emergency department visits in the USA were due to poisoning caused by painkillers.

A report released on Nov 1 by the US Centers for Disease Control and Prevention entitled Vital Signs: Overdoses of Prescription Opioid Pain Relievers—United States, 1999—2008, provides comprehensive nationwide estimates for opioid drug sales, non-medical use of opioid pain relievers, and opioid drug death rates—all of which have increased substantially during the past decade. This picture suggests an epidemic of painkiller use in the USA. The number of deaths owing to painkiller overdose in the USA has quadrupled in the past decade (to 14 800 each year, or 40 daily), and is currently higher than the number of fatalities from illegal drugs such as cocaine and heroin combined, and in some states surpasses road accident fatalities. Likewise, the availability of opioid drugs in US pharmacies, hospitals, and doctors' offices has quadrupled from 1999 to 2010—an amount that is sufficient to medicate every American adult every 4 hours for a month. The report also mentions that 12 million Americans (one in 20) reported using opioid drugs for a non-medical purposes, mainly recreational, in the past year.

Although the report probably underestimates the true magnitude of painkiller misuse in the USA (stratification by intention of opioid use was not possible, death records often lack information about the type of drug used, and responders tend to under-report non-medical use of opioid drugs in surveys), it confirms risk groups for whom interventions should be tailored. Men, individuals aged 35—45 years, non-Hispanic whites and American Indians, and rural dwellers are more likely to die from a painkiller overdose. Poverty and unemployment have also now been linked to use of non-medical opioid drugs since US states with the largest poverty rates, and a high number of Medicaid users, were also those with the highest mortality rates from opioid drug overdose.

Although the problem of painkiller misuse and overdosing is preventable, its origin is complex. Painkillers are easily obtained in the USA from so-called pill mills—illegitimate pain clinics that provide opioid drugs without adequate evaluation or follow-up. Doctor shopping is another common practice by which opioid drug prescriptions are obtained by an individual from several different physicians. Chronic mild pain, such as back pain, headache, and arthritis, are most likely to be unnecessarily treated with opioid drugs by primary and family-care physicians, who also tend to overprescribe sedatives and muscle relaxants that have an additive effect with painkillers. Family medical cabinets provide easy access to opioid drugs—not only do 40% of drugs prescribed in the USA go unused, but seven out of ten medication misusers get their drugs from family or friends.

What are possible solutions to balance legitimate access to pain treatment with reduction of misuse of painkillers? There should be increased recognition that non-medical use of opioid drugs is frequently observed in illicit drug users, and that addiction is a multifaceted problem that is much more complex than easy access to a drug. Physicians must take responsibility to: first, screen patients, scrutinising medical and family history to look for past substance misuse problems; second, be properly trained in pain management, opioid pharmacology, and principles of misuse and addiction; and third, only prescribe painkillers as a last resort for management of chronic pain, and give shorter supplies for acute pain. Patients must be educated in safe use, storage, and disposal of painkillers. Finally, local and federal government must take a lead with legislative measures that monitor prescription practices and prevent misuse and diversion of prescription of opioid drugs. 48 US states have already approved the prescription drug management programme which uses electronic databases to track all painkiller prescriptions within a state.

It is a paradox that opioid drugs are creating opposite public health problems in developed and developing countries—one caused by abundance and excess, and the other from lack of access for pain relief, which is a violation of a basic human right. This profound discrepancy must become a priority for policy makers and prescribers to properly balance opioid availability and misuse, and focus efforts on control of opioid demand rather than supply.

For more on the CDC report on painkillers in the USA see http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6043a4.htm?s_cid=mm6043a4_w

Why Drug Safety Should Not Take a Back Seat to Efficacy

2011-10-29T18:40:00.000-07:00

Citation: The PLoS Medicine Editors (2011) Why Drug Safety Should Not Take a Back Seat to Efficacy. PLoS Med 8(9): e1001097. doi:10.1371/journal.pmed.1001097

Published: September 27, 2011

Copyright: © 2011 PLoS Medicine Editors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors are each paid a salary by the Public Library of Science, and they wrote this editorial during their salaried time.

Competing interests: The authors' individual competing interests are athttp://www.plosmedicine.org/static/editorsInterests.action. PLoS is funded partly through manuscript publication charges, but the PLoS Medicine Editors are paid a fixed salary (their salary is not linked to the number of papers published in the journal).

* E-mail: medicine_editors@plos.org

The PLoS Medicine Editors are Virginia Barbour, Jocalyn Clark, Susan Jones, Melissa Norton, Paul Simpson, and Emma Veitch.

Provenance: Written by editorial staff; not externally peer reviewed.

Historically, the evaluation of harmful effects resulting from prescription drug use has been considered less important than demonstrating drug efficacy, yet the harms caused by specific adverse drug reactions are a major, and avoidable, contributor to hospitalizations and deaths [1]. There are many reasons (both scientific and social) why reliable data on harmful effects may only emerge well after drug approval and marketing [2]. Some evidence suggests that drugs approved under a rapid regulatory review process may be more likely to show problems with safety post-marketing than drugs that go through a slower evaluation process [3]. And debates continue about the best ways to meaningfully synthesize and interpret data on the possible harmful effects of drugs—for example, how passive surveillance systems (spontaneous reports of suspected adverse reactions) should be improved, whether new drugs should go through a phased launch process with enhanced safety evaluations, and whether risk mitigation strategies are appropriate for drugs with safety concerns.

One such debate—whether systematic reviews estimating the risk of harmful effects should use evidence from randomized trials or observational studies—seems finally to have been laid to rest. In a systematic overview published earlier this year in PLoS Medicine [4], Su Golder, Yoon Loke, and Martin Bland demonstrate that, for 19 specific drug–harm relationships, the evidence on magnitude of risk for each particular harm discovered through systematic reviews of randomized trials was, on average, no different from the evidence assembled via systematic reviews of observational studies. This is an important finding, although perhaps counterintuitive: it is easy to imagine that observational studies would be so plagued by confounding that the estimates of risk of harm they generate could be biased away from true effects. The implications of this study for future evaluations of drug safety are clear: systematic reviewers should consider all types of evidence in trying to build a complete picture of harms associated with drug treatments.

In another study published this week in PLoS Medicine [5], Patricia McGettigan and David Henry report their re-evaluation of one specific and much-studied harmful effect—that of cardiovascular risk associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs). Many previous systematic reviews have been conducted, largely using evidence from randomized trials, but these trials have generally captured only small numbers of cardiovascular events and have focused mainly on a small range of specific NSAIDs. By revisiting observational data in their systematic review, Henry and colleagues were able to form a fuller profile of the cardiovascular risks associated with use of a much wider group of NSAIDs, across dose ranges and in population settings, than had previously been the case. Broadly, their findings correlate closely with those of systematic reviews of trial data, but also show that there seems to be no “safe” lower dose for cardiovascular risk associated with certain NSAIDs, such as rofecoxib and diclofenac.

These studies together highlight the importance of data from high-quality observational studies in enabling estimation of the risk of harms associated with specific drug treatments. Passive surveillance is still crucial for providing early warning signals and generating new hypotheses about possible harms associated with specific approved drugs. However, new hypotheses emerging from such surveillance must subsequently be explicitly tested, preferably using study designs that can incorporate data on the size of the exposed population (such as cohort or record linkage studies). Such studies can therefore estimate the relative increase in risk associated with exposure, which is difficult or impossible to calculate from passive surveillance data.

A new initiative established by the European Medicines Agency (ENCEPP, the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance [6],[7]) seeks to promote the conduct of such studies and establish standards for post-marketing safety evaluations. Given the diversity of designs and multiple possible sources of bias in pharmacoepidemiology, this will not be an easy job. But the initiative is already showing signs of setting high standards in some areas. Studies conducted solely by industry will not be eligible to qualify for ENCEPP approval; studies must be publicly registered before collection of data, and protocols and datasets must be released (with some restrictions relating to data privacy) in a timely way after completion. Some vague wording in the ENCEPP code of conduct remains, however: “datasets” can be interpreted to mean analyzed, not raw, data, meaning that other investigators may not be able to exploit the full potential of the data in conducting reanalyses. Critically, ENCEPP can still potentially approve studies funded by the pharmaceutical industry, with involvement of industry partners in design and analysis, providing the study's lead investigator is based within an ENCEPP-approved center. More worryingly, the code allows for industry sponsors to retain control of datasets; this, and other provisions, may enable conflicts of interest to creep in during study design or data analysis.

Clearly, for post-approval safety studies, one size will not fit all. Conduct and reporting are unlikely to be standardizable in the same way as has been possible for randomized trials, in which there is agreement on what information needs to be registered about the study and when [8], and specific standards for the reporting of studies, such as CONSORT [9], are widely accepted. The ENCEPP guidance avoids normative statements about study design, instead preferring to highlight the methodological challenges and multiple sources of bias that plague analysis and interpretation of data. However, these challenges should not discourage investigators, regulators, and patients from demanding a higher safety standard for approved drugs. Higher standards will require both greater transparency—in revealing what studies are being conducted and what data that have been generated—and greater willingness of funders to support new studies specifically addressing drug safety.

Author Contributions Top

Wrote the first draft: EV. Contributed to the writing of the paper: VB JC SJ MN PS.

References Top

Pirmohamed M, James S, Meakin S, Green C, Scott AK, et al. (2004) Adverse drug reactions as cause of admission to hospital: Prospective analysis of 18,820 patients. BMJ 329: 15–19. FIND THIS ARTICLE ONLINE
Strom B (2004) Potential for conflict of interest in the evaluation of suspected adverse drug reactions. JAMA 292: 2643–2646. FIND THIS ARTICLE ONLINE
Carpenter D, Zucker EJ, Avorn J (2008) Drug-review deadlines and safety problems. N Engl J Med 358: 1354–1361. FIND THIS ARTICLE ONLINE
Golder S, Loke YK, Bland M (2011) Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: Methodological overview. PLoS Med 8(5): e1001026. doi:10.1371/journal.pmed.1001026.
McGettigan P, Henry D (2011) Cardiovascular Risk with non-steroidal anti-inflammatory drugs: Systematic review of population-based controlled observational studies. PLoS Med 8(9): e1001098. doi:10.1371/journal.pmed.1001098.
European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. Home page. Available: http://www.encepp.eu/.
Schneeweiss S, Avorn J (2011) Postmarketing studies of drug safety. BMJ 342: d342. FIND THIS ARTICLE ONLINE
Laine C, Horton R, DeAngelis CD, Drazen JM, Frizelle FA, et al. (2007) Clinical trial registration — Looking back and moving ahead. N Engl J Med 356: 2734–2736. FIND THIS ARTICLE ONLINE
CONSORT: Transparent Reporting of Trials. Home page. Available: http://www.consort-statement.org/.

Pioglitazone and bladder cancer

2011-10-28T06:52:00.000-07:00

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The Lancet, Volume 378, Issue 9802, Page 1544, 29 October 2011

doi:10.1016/S0140-6736(11)61663-2 Cite or Link Using DO

Pioglitazone and bladder cancer

Robert Elford Ryder a

In June, 2011, the French and German regulatory bodies suspended pioglitazone over the risk of bladder cancer. The European Medicines Agency (EMA) considered the issue and, on July 21, 2011, concluded that there did seem to be a small increased risk of bladder cancer with pioglitazone.1 Given this, and concerns about increased fractures and heart failure with pioglitazone,2 it is not surprising that, in a recent Lancet webcast,3 thiazolidinediones were lumped with sibutramine and rimonabant as drugs that have recently “bombed out”. And yet type 2 diabetes is more than anything a disease of people dying prematurely of cardiovascular disease and there is substantial evidence that pioglitazone causes cardiovascular benefit.2 The widespread blindness to this evidence is attributable to the well known “failure” of the primary composite endpoint in pioglitazone's randomised controlled trial, PROactive.4 But was this “failure” real?

Table 3 of the original Lancet publication of PROactive in 20054 shows that the first six factors in PROactive's primary composite endpoint: death, non-fatal myocardial infarction, silent myocardial infarction, stroke, leg amputation, and acute coronary syndrome are all less for pioglitazone than placebo and statistics show significant benefit for pioglitazone. It is only when the bottom two lines in the table—coronary and leg revascularisation—are added in that significance is lost. This outcome might be explained by pioglitazone preserving people from death, myocardial infarction, acute coronary syndrome, and leg amputation to be available for coronary or leg revascularisation.2 Thus pioglitazone as an agent of cardiovascular benefit would reduce the need for coronary and leg revascularisation in some patients while increasing the number of patients available for these procedures, making it impossible to come to any conclusion on the basis of procedure-based endpoints.

Pioglitazone reduces glycated haemoglobin (HbA1c) and, by implication, microvascular complications, and substantially reduces the need for insulin.4 Furthermore, on the basis of the pathophysiology and progress of type 2 diabetes with time, there is a strong case that current ideal management would involve aggressive treatment combining metformin, pioglitazone, and agonists of the glucagon-like peptide 1 receptor with a target HbA1c of less than 42 mmol/mol.5 It is worth noting that this combination of agents obviates the cost of home glucose monitoring and is devoid of hypoglycaemia risk.

Despite the EMA's conclusion over bladder cancer risk, the overall risk—benefit balance remains strongly in favour of continued use of pioglitazone, especially in patients with ischaemic heart disease (but without heart failure) or stroke.2

I have previously received educational sponsorship, speaker fees, and consultancy fees from several pharmaceutical companies including Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi-Aventis, and Takeda.

References

1 European Medicines Agency. European Medicines Agency recommends new contra-indications and warnings for pioglitazone to reduce small increased risk of bladder cancer: benefit-risk balance remains positive in a limited population of type 2 diabetics.http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2011/07/WC500109176.pdf. (accessed July 28, 2011).

2 Ryder REJ. Pioglitazone: an agent which reduces stroke, myocardial infarction and death and is also a key component of the modern paradigm for the optimum management of type 2 diabetes. Br J Diabetes Vasc Dis 2011; 11: 113-120. PubMed

3 Zimmet P. Controversies in diabetes: getting to the heart of the problem. http://www.thelancet.com/education/at-the-limits/cardiology-and-diabetes-2011/controversies-in-diabetes. (accessed July 28, 2011).

4 Dormandy JA, Charbonnel B, Eckland DJ, et alon behalf of the PROactive investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366: 1279-1289. Summary | Full Text | PDF(165KB) | CrossRef | PubMed

5 DeFronzo RA. Banting lecture: from the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58: 773-795. CrossRef | PubMed

Atomoxetina y alteraciones cardiovasculares

2011-10-25T06:39:00.000-07:00

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Eli Lilly Canada Inc., en colaboración con Health Canada, está notificando a los profesionales sanitarios y pacientes nuevos datos de seguridad importantes provenientes de estudios clínicos, en relación al riesgo de
aumento de la presión arterial y del ritmo cardíaco asociados con el uso de atomoxetina (Strattera), que es un inhibidor selectivo de la recaptación de noradrenalina indicado para el tratamiento de síndrome de déficit de atención / hiperactividad (TDAH) en niños y adultos.
La atomoxetina puede aumentar la frecuencia cardíaca y presión arterial. Tener en cuenta las siguientes recomendaciones:
a.. La atomoxetina está contraindicada en pacientes con enfermedad cardiovasculares sintomática, hipertensión moderada a severa o alteraciones cardiovasculares graves cuya condición se espera que se deteriore si se
experimentaron aumentos en la presión arterial o del ritmo cardíaco que pueden ser clínicamente importantes.

b.. Atomoxetina debe usarse con precaución en pacientes cuya patología subyacente podría empeorar por el aumento de la presión arterial o de la frecuencia cardiaca, como pacientes con hipertensión, taquicardia o
enfermedad cardiovascular o cerebrovascular.

c.. Atomoxetina debe usarse con precaución en pacientes con síndrome de QT largo congénita o adquirida, o un historial familiar de prolongación del intervalo QT.

d.. Antes de iniciar el tratamiento con atomoxetina y durante el seguimiento del curso del tratamiento, los pacientes deben ser evaluados para investigar la existencia de alteraciones cardiovasculares o cerebrovasculares pre-existentes o subyacentes.

e.. Se recomienda medir la frecuencia cardiaca y presión arterial en todos los pacientes antes del inicio del tratamiento con atomoxetina, después de aumentar la dosis, y periódicamente durante el tratamiento para
detectar posibles aumentos clínicamente importantes, en particular durante los primeros meses de la terapia.

Un reciente análisis de datos combinados de ensayos clínicos controlados y no controlados, patrocinados por Eli Lilly han indicado que, aproximadamente el 25% de los 8417 los pacientes pediátricos tratados con atomoxetina,
experimentó un aumento de la presión arterial de 10 mmHg y 5,8% un aumento de 20 mmHg, mientras que se registro un aumento de la frecuencia de 10 latidos por minuto (lpm) en el 33% de los pacientes y de 20 lpm en el 12% de los pacientes. Estos aumentos podrían representar un riesgo para algunos pacientes. En pacientes adultos con TDAH se ha observado aumento de la presión arterial y del ritmo cardíaco en una proporción similar

La monografía del producto canadiense de Stratteraha sido revisada.

Fuente: Martin Cañas. Lista Drugs in spanish
recientemente para incluir estos nuevos hallazgos importantes de seguridad.
Una copia de la monografía de producto más actualizada se puede encontrar
en: http://webprod3.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp

Fuente:
Health Canada. STRATTERA (atomoxetine) - Association with Increased Blood
Pressure and Increased Heart Rate - For Health Professionals. October 21,
2011
http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2011/strattera_2_hpc-cps-eng.php

Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia

2011-10-15T10:31:00.000-07:00

Image via WikipediaBAILIE, G. R., MASON, N. A. and VALAORAS, T. G. (2010), Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Hemodialysis International, 14: 47–54. doi: 10.1111/j.1542-4758.2009.00409.x

Abstract

There is limited safety information about ferric carboxymaltose (FCM), a new intravenous iron preparation. This randomized, crossover study compared the safety and tolerability of double-blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia. Subjects (559) with iron deficiency anemia received a dose of either FCM (15 mg/kg, maximum 1000 mg) over 15 minutes or placebo on day 0. On day 7, subjects received the other agent. Safety evaluations were performed on days 7 and 14. The primary endpoint was the incidence of treatment-emergent adverse events during each 7-day study period. During the first 24 hours and during the 7-day treatment period, at least one treatment-emergent adverse event was experienced by 15.0% and 29.3% of subjects after FCM and 11.4% and 19.7% after placebo, respectively. Most were classified as Grade 1 or 2. Six subjects had Grade 3 treatment-emergent adverse events after FCM and 9 subjects after placebo. One subject had a Grade 4, and 1 subject had a Grade 5 treatment-emergent adverse event, but neither was considered study drug-related. During the first 24 hours of the treatment period, drug-related adverse events were reported in 9.3% of subjects receiving FCM and 4.8% receiving placebo. Of drug-related Grade 3 events, 4 subjects received FCM and 5 subjects received placebo. Administration of FCM (15 mg/kg, maximum of 1000 mg) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia.

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Early Communication of an Ongoing Safety Review on Bisphosphonates

2011-10-14T13:18:00.000-07:00

Early Communication of an Ongoing Safety Review on Bisphosphonates: Alendronate (Fosamax, Fosamax Plus D), Etidronate (Didronel), Ibandronate (Boniva), Pamidronate (Aredia), Risedronate (Actonel, Actonel W/Calcium), Tiludronate (Skelid), and Zoledronic acid (Reclast, Zometa)

The FDA has issued new information about this safety issue, see current information.

10/1/2007

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

Publications in a recent issue of The New England Journal of Medicine have raised the question about the association of atrial fibrillation with the use of bisphosphonates. FDA has reviewed some safety data and requested additional data to further evaluate the risk of atrial fibrillation in patients who take bisphosphonates.

An article and an accompanying letter to the editor in the May 3, 2007, issue of The New England Journal of Medicine describe increased rates of serious atrial fibrillation (defined by the authors as life-threatening or resulting in hospitalization or disability) in two different studies of older women with osteoporosis treated with the bisphosphonates, Reclast and Fosamax. In both studies, more women who received one of the bisphosphonates (Reclast-1.3% or Fosamax-1.5%) reportedly developed serious atrial fibrillation as compared to women who received placebo (Reclast study-0.5%, Fosamax study-1.0%). In both studies, the rates of all atrial fibrillation (serious plus nonserious) were not significantly different between groups treated with bisphosphonate versus placebo.

What does FDA know about this concern?

The FDA reviewed spontaneous post-marketing reports of atrial fibrillation reported in association with oral and intravenous bisphosphonates and did not identify a population of bisphosphonate users at increased risk of atrial fibrillation. In addition, as part of the data review for the recent approval of once-yearly Reclast for the treatment of postmenopausal osteoporosis, the FDA evaluated the possible association between atrial fibrillation and the use of Reclast. Most cases of atrial fibrillation occurred more than a month after drug infusion. Also, in a subset of patients monitored by electrocardiogram up to the 11th day following infusion, there was no significant difference in the prevalence of atrial fibrillation between patients who received Reclast and patients who received placebo.

Atrial fibrillation is a heart rhythm disorder common in individuals 65 years old and older, the same age range of many of the patients studied in the article published in The New England Journal of Medicine. Upon initial review, it is unclear how these data on serious atrial fibrillation should be interpreted. Therefore, FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of bisphosphonates at this time.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. FDA is seeking additional data to allow for an in-depth evaluation of the atrial fibrillation issue for the entire class of bisphosphonates. It may take up to 12 months to complete the evaluation at which time FDA will communicate the conclusions and any resulting recommendations to the public. Moreover, FDA is continuing to monitor spontaneous post-marketing reports of atrial fibrillation reported in patients who have taken bisphosphonates.

Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis. Bisphosphonates are also used to slow bone turnover in patients with Paget’s disease of the bone and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. There are 7 FDA-approved bisphosphonates: alendronate (Fosamax, Fosamax Plus D), etidronate (Didronel), ibandronate (Boniva), pamidronate (Aredia), risedronate (Actonel, Actonel W/Calcium), tiludronate (Skelid), and zoledronic acid (Reclast, Zometa).

The FDA urges both healthcare professionals and patients to report side effects from the use of bisphosphonates to the FDA's MedWatch Adverse Event Reporting program, using the contact information at the bottom of this page.

Related Information

September 2011 Safety Labeling Changes

2011-10-14T12:58:00.000-07:00

The MedWatch September 2011 Safety Labeling Changes posting includes 34 products with safety labeling changes to the following sections: BOXED WARNINGS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, PATIENT PACKAGE INSERT, and MEDICATION GUIDE.

The "Summary Page" provides a listing of drug names and safety labeling sections revised:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm274280.htm

Clicking on a drug product name in the Summary View will take you to the "detailed view" page, which identifies safety labeling sections and subsections revised, along with a brief summary of new or modified safety information.

The following drugs had modifications to the BOXED WARNINGS, CONTRAINDICATIONS and WARNINGS sections:

Detrol (tolterodine tartrate) tablets and Detrol LA (tolterodine tartrate) extended release tablets
Orap (pimozide) 1 mg and 2 mg tablets
Anzemet (dolasetron mesylate) tablets and Anzemet (dolasetron mesylate) injection
Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) tablets
Avastin (bevacizumab)
Cymbalta (duloxetine hydrochloride)
Effient (prasugrel hydrochloride) 5 mg and 10 mg Tablets
Ellence (epirubicin hydrochloride) injection
Istodax (romidepsin) for Injection
Lexiscan (regadenoson) Injection
MultiHance (gadobenate dimeglumine) injection
Nicorette (nicotine polacrilex) 2 mg and 4mg gum [OTC]
Procardia (nifedipine) 10 mg Capsules
Procardia XL (nifedipine) 30 mg, 60 mg, and 90 mg Extended Release Capsules
Stimate (desmopressin acetate) 1.5 mg/mL nasal spray
Sustenna (paliperidone palmitate) Extended-Release Injectable Suspension for intramuscular use
Risperdal (risperidone) tablets, oral solution
Risperdal M-Tab (risperidone) orally disintegrating tablets
Risperdal Consta (risperidone) long-acting injection
Xenon Xe 133 Gas, 10 and 20 mCi, septum sealed glass vial
Zofran (ondansetron hydrochloride) injection and premixed injection
Zofran (ondansetron hydrochloride) tablets, oral solution, and orally disintegrating tablets

Some Vitamin, Mineral Supplements May Be Harmful

2011-10-13T15:27:00.000-07:00

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Source: Family Practice News

Some Vitamin, Mineral Supplements May Be Harmful

By: SHARON WORCESTER, Family Practice News Digital Network

Several commonly used vitamin and mineral supplements were significantly associated with increased total mortality risk in 38,772 older women from the Iowa Women’s Health Study who were followed for a mean of 19 years.

Supplemental iron was most strongly associated with increased mortality (hazard ratio of 1.10 in a fully adjusted model), Jaakko Mursu, Ph.D., of the University of Eastern Finland, Kuopio, and colleagues reported in the Oct. 10 issue of Archives of Internal Medicine.

The use of multivitamins, vitamin B₆, folic acid, magnesium, zinc, and copper also was associated with a higher risk of mortality (hazard ratios, 1.06, 1.10, 1.15, 1.08, 1.08, and 1.45, respectively) after adjustment for age, education level, place of residence, diabetes mellitus, high blood pressure, body mass index, waist to hip ratio, hormone therapy, physical activity, smoking status, alcohol intake, energy intake, saturated fatty acids intake, whole grain products intake, and fruit and vegetable intake.

Conversely – and in contrast to findings from some prior studies – calcium supplementation was associated with decreased mortality risk in adjusted models (hazard ratio of 0.91 for the fully adjusted model), the investigators found (Arch. Intern. Med. 2011;171:1625-33).

Participants in the Iowa Women’s Health Study were enrolled in 1986 and those included in the current study had a mean age of 61.6 years. Participants completed a 16-page self-administered questionnaire that included information on food frequency and supplement use. Additional self-reports were provided in 1997 and 2004. As of Dec. 31, 2008, 40% of those included in the current analysis had died.

Self-reported supplement use increased over time, with 62.7%, 75.1%, and 85.1% reporting the use of at least one supplement daily in the 1986, 1997, and 2004 questionnaires, respectively.

The most commonly used supplements were calcium, multivitamins, vitamin C, and vitamin E; the most commonly used combinations were calcium and multivitamins; calcium, multivitamins, and vitamin C; and calcium and vitamin C.

"Although we cannot rule out benefits of supplements, such as improved quality of life, our study raises a concern regarding their long-term safety."

On analyses performed for shorter follow-up intervals of 10, 6, and 4 years, the findings for iron and calcium were replicated; about 15% of the deaths in original participants occurred in each of the following periods: 1986 through 1996, 1997 through 2003, and 2004 through 2008.

"In multivariable adjusted analyses across the shorter follow-up intervals, beginning with the baseline and each follow-up questionnaire, the most consistent findings ... were for supplemental iron (hazard ratios,1.20, 1.43, and 1.56...) and calcium (0.89, 0.90, 0.88)," the investigators said.

Furthermore, increased consistency of use of iron was associated with increased mortality risk; the hazard ratio for mortality (versus nonuse) for those who reported using iron at only one survey was 1.35, compared with 1.62 and 1.60 for use at two and at all three surveys, respectively, they said.

The findings, though observational, are concerning given the popularity of dietary supplements, the investigators said, noting that about half of all adults were using supplements in 2000, and that 66% of women participating in the Iowa Women’s Health Study used at least one supplement daily at baseline, with an increase to 85% in 2004. More than a quarter of participants used four or more.

"Supplemental nutrient intake clearly is beneficial in deficiency conditions. However, in well-nourished populations, supplements often are intended to yield benefit by preventing chronic disease," the investigators noted, adding that studies have produced inconsistent results in regard to the benefits and harms of supplementation.

Several randomized controlled trials and meta-analyses – particularly those evaluating the use of calcium and vitamins B, C, D, and E – have shown no benefit in terms of total mortality rate and in some cases have shown possible harm, they said.

This study provides further evidence that most dietary supplements are unrelated to total mortality rate, and that some are associated with increased total mortality rate.

The strengths of this study are the large sample size and longitudinal design, as well as the fact that the women were questioned three times about diet and supplement use during the course of the follow-up.

"The use of repeated measures enabled evaluation of the consistency of the findings and decreased the risk that the exposure was misclassified," the investigators wrote.

The limitations of the study include the potential for residual confounding despite extensive adjustment, and the possibility that some supplements may have been taken for "reasonable cause in response to symptoms or clinical disease."

Furthermore, 99.2 % of women in the Iowa Women’s Health Study were white, thus generalization to other populations, ethnic groups, and men is problematic.

"Although we cannot rule out benefits of supplements, such as improved quality of life, our study raises a concern regarding their long-term safety ... it is not advisable to make a causal statement of excess risk based on these observational data; however, it is noteworthy that dietary supplements, unlike drugs, do not require rigorous (randomized controlled trial) testing, and observational studies are often the best available method for assessing the safety of long-term use," they wrote.

Therefore, based on existing evidence, they argue that there is little justification for the general and widespread use of dietary supplements.

"We recommend that they be used with strong medically based cause, such as symptomatic nutrient deficiency disease," they concluded.

"Until recently, the available data regarding the adverse effects of dietary supplements has been limited and grossly underreported."

This "large, well-designed, and well-conducted" trial adds to the existing evidence that certain supplements can be harmful, and the findings concur with those of other recent observational studies, Dr. Goran Bjelakovic and Dr. Christian Gluud said in an editorial accompanying the report (Arch. Intern. Med. 2011;171:1633-4).

"The belief that antioxidant supplements are beneficial seems likely to have resulted from a collective error. Perhaps oxidative stress is one of the keys to extension of our life span," they suggested.

Indeed, the shift in the use of dietary supplementation for prevention of deficiency to use for promoting wellness and prevention of diseases – with many consumers believing that supplements are safe for use without the supervision of their physician – is problematic.

"Until recently, the available data regarding the adverse effects of dietary supplements has been limited and grossly underreported. We think the paradigm ‘the more the better’ is wrong," they said.

Rather, there are likely risks with both insufficient and too-large intake, added Dr. Bjelakovic and Dr. Gluud, both of whom are with the Copenhagen trial unit, center for clinical intervention research, Cochrane Hepato-Biliary Group, Rigshospitalet, Copenhagen, University Hospital.

"Therefore, we believe that politicians and regulatory authorities should wake up to their responsibility to allow only safe products on the market," they said, also noting that in a well-nourished population, the use of vitamin and mineral supplements as a preventive measure should not be recommended.

A possible exception based on these and other findings is with vitamin D₃ supplementation, particularly when there is insufficient vitamin D supply from the sun and diet; this may apply to older women, and perhaps older men. The matter of calcium supplementation may require further study, they said.

This study was partially supported by a grant from the National Cancer Institute and by grants from the Academy of Finland, the Finnish Cultural Foundation, and the Fulbright program. One of the study authors (David R. Jacobs Jr., Ph.D.) reported being an unpaid member of the scientific advisory board of the California Walnut Commission. None of the other authors had relevant financial disclosures to report. Neither Dr. Bjelakovic nor Dr. Gluud had relevant financial disclosures to report.

Risk of Pulmonary Arterial Hypertension with dasatinib

2011-10-11T15:11:00.000-07:00

Sprycel (dasatinib): Drug Safety Communication - Risk of Pulmonary Arterial Hypertension

AUDIENCE: Hematology, Oncology

ISSUE: FDA notified healthcare professionals that Sprycel (dasatinib) may increase the risk of a rare but serious condition in which there is abnormally high blood pressure in the arteries of the lungs (pulmonary arterial hypertension [PAH]). Symptoms of PAH may include shortness of breath, fatigue, and swelling of the body (such as the ankles and legs). In reported cases, patients developed PAH after starting Sprycel, including after more than one year of treatment.

Information about this risk has been added to the Warnings and Precautions section of the Sprycel drug label.

BACKGROUND: Sprycel (dasatinib) is used to treat certain adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

RECOMMENDATION: Healthcare professionals should evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to starting Sprycel and also during treatment. If PAH is confirmed, Sprycel should be permanently discontinued.

Read the MedWatch safety alert, including a link to the Drug Safety Communication, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm275176.htm

Related articles

Effects of DES Exposure Follow Women for Decades

2011-10-06T21:42:00.000-07:00

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The teratogenic effects of diethylstilbestrol (DES) have continued to exact a heavy toll throughout the lifetime of women who were exposed to the drug in utero, investigators reported.

The lingering effects of DES encompassed a broad spectrum of health disorders, ranging from infertility and a variety of pregnancy complications to a significantly elevated risk of breast and cervical cancer, according to Robert N. Hoover, MD, ScD, of the National Cancer Institute in Bethesda, Md., and colleagues.

All comparisons of women exposed to DES with an unexposed control group demonstrated statistically significant differences, most of which were at least twice as high in exposed women, they reported in the Oct. 6 issue of the New England Journal of Medicine.

"Our study linked 12 adverse health outcomes in women to their exposure to DES in utero, with most risks increased by a factor of more than two as compared with the risks among unexposed women," Hoover and co-authors wrote in their summation.

"For most outcomes, risks were higher among women with vaginal epithelial changes, a histologic marker of high-dose DES exposure, than for women without this condition," they continued.

"Although DES has not been prescribed for pregnant women in the U.S. for 40 years, adverse outcomes continue to occur in women exposed in utero, and continued monitoring, as is ongoing in this cohort, for established and unexpected adverse outcomes seems prudent."

Developed in 1938 as the first synthetic estrogen, DES was used almost immediately to prevent pregnancy complications. The use continued until clinical trials conducted in the 1950s showed no pregnancy-associated efficacy for the hormone.

In the 1960s, an unusual cluster of vaginal and cervical adenocarcinoma was identified in adolescent girls and young women. Subsequent investigation revealed a strong association between the cancers and in utero exposure to DES, the authors wrote in their introduction.

Additional studies of women exposed to DES showed developmental defects in the genital tract and an increased rate of several complications of pregnancy, they continued.

Concern about the clinical significance and magnitude of the findings led to longer-term studies of women exposed to DES in utero.

In the early 1990s, investigators at NIH and multiple collaborating institutions combined participants in three large cohort studies begun in the 1970s and contacted all of the surviving women and enrolled them in a systematic assessment and follow-up study.

Investigators compared the exposed and unexposed women with respect to 12 adverse outcomes associated with DES exposure, including cumulative risk to age 45 for reproductive outcomes and to 55 for other outcomes.

The final analysis included 4,653 DES-exposed women and 1,955 women who were not exposed. The average age at follow-up was 48.

The comparisons showed significantly higher rates of adverse outcomes in the DES-exposed women.

Infertility: 33% versus 15.5%, HR 2.37, 95% CI 2.05 to 2.75
Spontaneous abortion: 50.3% versus 38.6%, HR 1.64, 95% CI 1.42 to 1.88
Preterm delivery: 53.3% versus 17.8%, HR 4.68, 95% CI 3.74 to 5.86
Loss of second-trimester pregnancy: 16.4% versus 1.7%, HR 3.77, 95 CI 2.56 to 5.54
Ectopic pregnancy: 14.6% versus 2.9%, HR 3.72, 95% CI 2.58 to 5.38
Preeclampsia: 26.4% versus 13.7%, HR 1.42, 95% CI 1.07 to 1.89
Stillbirth: 8.9% versus 2.6%, HR 2.45, 95% CI 1.33 to 4.54
Early menopause: 5.1% versus 1.7%, HR 2.35, 95% CI 1.67 to 3.31
Grade 2 or higher cervical intraepithelial neoplasia: 6.9% versus 3.4%, HR 2.28, 95% CI 1.59 to 3.27
Breast cancer: 3.9% versus 2.2%, HR 1.82, 95% CI 1.04 to 3.18

Hazard ratios for the adverse outcomes tended to be higher among women with vaginal epithelial changes, consistent with high-dose DES exposure.

The study was supported by the National Cancer Institute.

Co-author Stanley J. Robboy disclosed a relationship with UCB, Belgium. Co-author Beth Y. Karlan disclosed a relationship with IRIS International.

Primary source: New England Journal of Medicine
Source reference:
Hoover RN, et al "Adverse health outcomes in women exposed in utero to diethylstilbestrol" N Engl J Med 2011; 365: 1304-1313.

Action Points

Explain that the teratogenic effects of diethylstilbestrol have continued to exact a heavy toll throughout the lifetime of women who were exposed to the drug in utero.
Point out that DES-exposed women had significantly higher rates of multiple adverse outcomes including increases in infertility, spontaneous abortion, preterm delivery, early menopause, grade 2 or higher cervical intraepithelial neoplasia, and breast cancer.

Evaluación de Medicamentos, Pamplona, España

2011-10-05T21:20:00.000-07:00

Image via WikipediaJuan Erviti Lopez, de la Sección de Información y Asesoría del Medicamento del Servicio de Prestaciones Farmaceuticas. SNS-O. Pamplona (España) nos comunica la publicación de los ultimo informes de evaluación de medicamentos

FET Numero 12. Citrato de fentanilo sublingual (Abstral®) en el dolor irruptivo del paciente oncologico:

/Una presentacion mas en la peligrosa y lucrativa moda de los fentanilos orales/

El fentanilo sublingual esta indicado solo en el dolor irruptivo en pacientes oncologicos, siempre y cuando el dolor de base persistente este controlado con terapia cronica con opiodes. La evidencia sobre su eficacia es escasa, solo un estudio frente a placebo. No hay estudios comparativos de las distintas formulaciones de fentanilo comercializadas, ni con otros opiodes de liberacion inmediata.
Es un opiode potente con un perfil de reacciones adversas similar y no mas seguro que otros. Requiere una fase de ajuste y titulacion de la dosis efectiva para cada paciente y no es posible el intercambio de las distintas formulaciones de fentanilo oral con la misma dosis, ya que no son equivalentes.
http://tinyurl.com/6j6b2kr

FET Numero 11. Liraglutida (Victoza®) en diabetes mellitus tipo 2
Similar a exenatida

• La liraglutida ha mostrado una eficacia comparable a glimepirida y ligeramente superior a insulina glargina y exenatida, aunque la relevancia clinica es escasa.
• Produce disminucion del peso comparable a la exenatida,mayor al inicio del tratamiento y en pacientes con alto indice de masa corporal.
• Los abandonos por efectos adversos y el perfil de seguridad es similar a exenatida. La incidencia de hipoglucemias es baja, aumentando cuando se combina con sulfonilureas.
• Existen incertidumbres sobre su seguridad cardiovascular, accion en tiroides, pancreatitis e inmunogenicidad. No hay informacion de su seguridad a largo plazo.
• No se dispone de datos de eficacia en las complicaciones de la diabetes ni de mortalidad
http://tinyurl.com/63fag8y

FET Numero 10. Ciclesonida (Alvesco®) en el tratamiento del asma persistente
...Y otro corticoide inhalado mas

Ciclesonida es un corticoide inhalado indicado en el tratamiento del control del asma persistente en adultos y adolescentes (?12 anhos). Eficacia a corto plazo similar a otros corticoides inhalados en asma leve-moderada.
No hay datos a largo plazo, ni en asma grave ni a dosis altas.
La imposibilidad de realizar ajustes individuales de la dosificacion, al estar solo comercializada la dosis de 160 ?g, limita la teorica ventaja de su administracion unica diaria.
http://tinyurl.com/6bzptbn

FET Numero 9. Dutasterida/Tamsulosina (Duodart®) en hiperplasia benigna de prostata
Asociar ¿para que?

La asociacion esta indicada en el tratamiento de los sintomas de moderados a graves de la HBP y para la reduccion del riesgo de retencion aguda de orina y cirugia en estos pacientes. En el unico estudio publicado, la asociacion no ha conseguido demostrar su superioridad frente a dutasterida en monoterapia en la reduccion de riesgo de retencion urinaria aguda o necesidad de cirugia.
Las reacciones adversas fueron mas frecuentes en el grupo tratado con la asociacion que en los de monoterapia. La incidencia de insuficiencia cardiaca fue mayor en los pacientes tratados con tamsulosina sola o combinada y las alteraciones en la eyaculacion y la disfuncion erectil fueron mayores entre los pacientes que recibieron dutasterida sola o combinada.
La FDA ha emitido una alerta en la que advierte que los inhibidores 5-alfa-reductasa pueden aumentar el riesgo de cancer de prostata de alto grado.
http://tinyurl.com/6duc9yk

Martín Cañás
Fundación Femeba
La Plata
(Argentina)
farmacol@femeba.org.ar