Infections, oral anticoagulant therapy, cotrimoxazole and ciprofloxacin

The newsletter on Patient Safety of the Ministry’s Quality Agency has published a new edition with articles of great interest. Among them, one published in Archives of Internal Medicine that associate the increased occurrence of upper gastrointestinal (UGI) tract hemorrhage in patients undergoing oral anticoagulant therapy with warfarin, if they are prescribed cotrimoxazole or ciprofloxacin, for a lower urinary tract infection (UTI), for example.

The researchers conducted a population-based, nested case-control study. Cases were hospitalized with UGI tract hemorrhage. For each case, we selected up to 10 age- and sex-matched control subjects. We calculated adjusted odds ratios (aORs) for exposure to cotrimoxazole, amoxicillin trihydrate, ampicillin trihydrate, ciprofloxacin hydrochloride, nitrofurantoin, and norfloxacin within 14 days before the UGI tract hemorrhage.Cases were patients taking warfarin and who were hospitalized with UGI tract hemorrhage. 2151 cases and 21434 controls were identified (10 for each). Researchers investigated whether the patients had taken in the days before cotrimoxazole, amoxicillin or ampicillin, ciprofloxacin, nitrofurantoin and norfloxacin (antibiotic commonly used to treat UTIs). Cotrimoxazole was even associated with increased risk of UGI hemorrhage, with an OR of 3.84. It also occurred with ciprofloxacin, with an OR of 1.94. Amoxicillin, ampicillin, nitrofurantoin and norfloxacin were not associated with an increased risk.

Although cotrimoxazole is rarely used in Spain at present, ciprofloxacin is usually prescribed. This article provides guidelines for a safer –and more rational- treatment of the UTIs or other location.

Fischer HD, Juurlink DN, Mamdani MM, Kopp A, Laupacis A. Hemorrhage during warfarin therapy associated with cotrimoxazole and other urinary tract anti-infective agents: a population-based study. Arch Intern Med 2010; 170 (7):617-21. [PMID: 20386005].


Posted by Fernando Palacio
English version by Erika Céspedes

Europe removes drugs containing rosiglitazone (Avandia®, Avandamet® and Avaglim®)

Finally, rosiglitazone (Avandia®) is no longer available in Europe.

In a previous post we discussed an article of The New York Times, which might help to explain why the FDA refuses its full withdrawal, although rosiglitazone is not better than pioglitazone, but causes more cardiovascular problems.

Yesterday, El País reported extensively on the ban, until Glaxo can "identify the group of patients in which the drug benefit exceeds the risks".

Avandia® sold 920 million Euros last year, and had arrived in 2006 to more than 2000 million. The question is: If the alert was given, and there are equally effective alternative medications, and safer, why was it still prescribed?

+ Info: - Spanish Agency for Drugs and Health Care Products (AEMPS):

Patient information note on the suspension of marketing of drugs containing rosiglitazone (Avandia ®, Avandamet ®, Avaglim ®)

Communication for professionals

- European Medicines Agency (EMA):

Press release: European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim

Questions and answers on the suspension of rosiglitazone-containing medicines (Avandia, Avandamet and Avaglim)


- In this blog:

GSK hid the rosiglitazone (Avandia) is associated with cardiovascular risk

GSK recibe una reprimenda de la FDA por ocultar datos sobre su antidiabético rosiglitazona (Avandia) (GSK receives a rebuke from the FDA for hiding data on its antidiabetic rosiglitazone Avandia)


Posted by Fernando Palacio
English version by Erika Céspedes

Again with blood glucose meters: Supplementary information

We recently echoed in this blog a warning from the Spanish Agency of Drugs and Health Care Products (AEMPS), referring to problems of interference in glucose meters.

Abbott Laboratories have corrected their test strips FreeStyle Lite, for not to interfere with certain medications at the time of measuring blood glucose in diabetic patients.

They have therefore changed the reactive enzyme, replacing PQQ-glucose-dehydrogensasa by glucose dehydrogenase-FAD, which is specific for the detection of glucose in blood.

To identify these new strips they have changed aspects of packaging and labeling, making it necessary to pay attention to these changes.

The Spanish Agency for Drugs and Health Care Products (AEMPS) has issued a supplementary information to the security note on possible errors in measurements of glucose in diabetic patients due to interference with certain treatments, which provides detailed information on laboratory changes.


See also in this blog:

Again with blood glucose meters

Beware with blood glucose meters


Posted by Juan José Jurado
English version of this post Jesús Moreno

GSK hid the Rosiglitazone (Avandia) is associated with cardiovascular risk

The New York Times has published an article which alleged that GlaxoSmithKline (GSK) has withheld the results of a study, organized by the very multinational pharmaceutical company, which showed an increased cardiovascular risk in patients treated with rosiglitazone (Avandia).

Rosiglitazone, a drug used in the treatment of diabetes, is also marketed in the European Union, in combination with Metformin (Avandamet) and Glimepiride (Avaglim).

This study, conducted prior to the approval of the product, comparing rosiglitazone with pioglitazone, concluded not only that it was not superior for treatment, but also produced an increased cardiovascular risk. Although the results were clearly unfavorable to the drug of GSK, the laboratory not only did not published them but, according to company files, deliberately concealed them, stealing relevant information for the approval of the regulatory agencies.

Currently, the agencies responsible for authorization of medicines in USA (FDA) and the European Union (EMEA), are assessing the safety of Rosiglitazone, after the publication last year of two studies concluding that it increases the likelihood of suffering serious cardiovascular problems and even death.

That is, new trials agree in indicating cardiovascular risks identified previously by the manufacturer in 1999 and hidden from the authorities, patients and professionals. Meanwhile thousands of patients, only about 80,000 in Spain, are taking a drug that some studies indicate may increase the risk of suffering a cardiovascular event like heart attack, stroke and even death.

There is a fierce debate in the FDA over the decision to take on Avandia, in which the director of new drugs, John Jenkins has defended the retention of the drug on the market, and has even informed GSK managers about the internal deliberations of the agency.

Rosemary Johann-Liang, an former member of that department of the FDA, who was sanctioned for recommending to emphasis Avandia's cardiovascular warnings in its package information leaflets, has now joined the voices calling for a change in the leadership of the FDA.

+ Info on NYT Diabetes Drug Maker Hid Test Data, Files Indicate

See also in this blog: GSK recibe una reprimenda de la FDA por ocultar datos sobre su antidiabético Rosiglitazona (Avandia)


Posted by Jesús Palacio
English version by Jesús Moreno and Erika Céspedes

The effects of on-screen, point of care computer reminders on processes and outcomes of care

A Cochrane review on on-screen computer reminders delivered to health professionals at the point of care, concludes that those ones produce only small to moderate improvements in both process and outcome of care.

Computer reminders are intended to help health care professionals to recall information that they may already know, but could forget easily when doing other activities of care. They also serve to support decisions, provide information or guidance in an accessible format at a particularly relevant. These reminders are able to address multiple topics, are automatic and come at the right time of care.

This Cochrane review found 28 studies that evaluated the effects of different on-screen reminders. The studies tested reminders to prescribe specific drugs, to warn about drug interactions, to provide vaccinations or to order tests.

The review found small to moderate benefits, that is, these reminders improved medical practice in a small percentage by measuring the results against the percentage of patients receiving care according to the reminder given to the professional (e.g. specific medication prescription, performance of a specific task such as sending to a medical specialist, etc.).

They also studied continuous process outcomes, for example, duration of treatment with antibiotics and various markers of disease or health status (e.g., mean blood pressure or cholesterol level). However, the results of improvement patients’ health also achieved small benefits.


Shojania KG, Jennings A, Mayhew A, Ramsay CR, Eccles MP, Grimshaw J. The effects of on-screen, point of care computer reminders on processes and outcomes of care.. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD001096. DOI: 10.1002/14651858.CD001096.pub2


See also in this blog: ¿Se cancelan las alertas sobre medicamentos en la prescripción electrónica?


Posted by Guadalupe Olivera
English version by Erika Céspedes

Beware with blood glucose meters

The Spanish Agency for Drugs and Health Care Products has issued a safety note on June 18 warning on the risk of possible errors in measurements of glucose obtained with some blood glucose meters using the enzyme as a reagent pyrroloquinoline quinone glucose dehydrogenase (GDH-PQQ ), interfering in these results some medications.

Meters that use this enzyme are Accu-Chek Sensor®, Accu-Chek Compact Plus®, Accu-Chek Compact®, Accu-Chek Aviva®, Accu-Chek Aviva Nano® , Accu-Chek Voicemate®, FreeStyle Lite® and Freestyle Freedom Lite®.

Drugs wich may interfere are Extraneal® , Orencia®, Octagamocta® and Adept® 4%.

This same warning has been published by the FDA in August 2009 (FDA Public Health Notification: Potentially Fatal Errors with GDH-PQQ * Glucose Monitoring Technology).

Both notes report that the use of these meters in patients undergoing treatment with outlined in the table medications, can produce abnormally high results detecting substances other than glucose that are generated from the administration of these drugs.

Worth noting that these drugs are not used routinely in primary care settings because the conditions for which are shown are monitoring, most of them specialized care. These patients are those undergoing peritoneal dialysis (Extraneal), patients with certain immune deficiencies situations or undergoing bone marrow transplantation (Octagamocta), patients with rheumatoid arthritis (Orencia), or patients undergoing abdominal surgery (Adept).

It is important therefore not to use these blood glucose meters in these patients.

With respect to the use of blood glucose meters, we also note that a valid result can come conditioned by other aspects of this process:

• Assessing the need for prior calibration of the meter.
• Improper storage of test strips.
• Ambient temperature.
• Insufficient blood volume.

Also, each meter has different methodologies for testing. Therefore, it is not advisable to make comparisons of results between different commercial laboratories.


Posted by Juan José Jurado
English version by Jesús Moreno

Proton pump inhibitors and risk of fracture

The FDA has issued a note, both for professionals and patients, reporting the revision of the prescription of the proton pump inhibitors to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine.

This information is based on the review of seven epidemiological studies that suggested that the increased risk of such fractures may depend on the dose, duration of the treatment or both.

At present, there is uncertainty about the magnitude of this risk. So, when prescribing PPIs, healthcare professionals should consider a lower dose or shorter duration of treatment, when required.

+ Info: Press release by the FDA

The widespread use of PPIs requires to take into account this risk, especially when deciding the appropriateness of the initiation or maintenance treatment of the treatment with these drugs.

There are several reliable publications on the appropriate of PPIs, for example, this synthetic and clear note of the Dirección General de Farmacia del Servicio Canario de Salud.


Posted by Guadalupe Olivera and Jesús Palacio
English version by Erika Céspedes