Differential Impact of Selective Serotonin Reuptake Inhibitors on Platelet Response to Clopidogrel: A Randomized, Double-Blind, Crossover Trial

SSRIs and other antidepressant medications constitute one of the most commonly prescribed drug classes that pharmacists will see in the community setting. When taken alone, any one of these medications can be a good treatment option for patients experiencing depression; however, these drugs can cause a patient who is taking multiple drugs  to experience significant interactions with his/her other medications. For this reason, it is crucial to know how the effects of other medications can be altered through this therapy.  This study analyzed the effects of two SSRIs (citalopram and fluvoxamine) on the blood thinning medication clopidogrel. These medications all work on the same CYP enzyme (CYP2C19)  and have opposing effects. Researches tested these medications on healthy individuals and found that fluvoxamine was the only drug that caused significant inhibition of clopidogrel action.

I think this is important to note because these medications are commonly utilized by patients and thus there is a high likelihood that they may be taken together. As pharmacists, we should be able to provide adequate care in response to possible drug-drug interactions. To do this, we have to be able to recognize when there could potentially be a problem in medication therapy. By taking the proper precautions when these situations arise, pharmacists will be more likely to help patients avoid adverse medical events associated to drug therapy methods.

Predictive Validity of Beers and STOPP Criteria to Detect Adverse Drug Events in the United States

One of the largest concerns among the geriatric pharmacy community is being able to predict adverse drug events from medications that are inappropriate within the elderly population.  To help with reducing these adverse outcomes and emergency department visits, most geriatric health providers often turn to recommendation resources such as Beers criteria or the Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP) for guidance on drugs that are potentially inappropriate medications (PIMs).  The issue with these criteria is a lack of research into how sensitive and accurate they are for predicting ADE or ED visits among the elderly who may have indications for the medications.

A recent study by members of the University of Arkansas, College of Pharmacy published in the Journal of American Geriatrics Society that assessed the predictive power of Beers and STOPP criteria for PIM in elderly populations.  The performed an eight-year retrospective cohort study on over 174,000 commercially insured patients over 65 years old, monitoring them for association between ADE and ED visits based on inappropriate medication use based on the criteria of either 2003 beers, 2012 Beers, or STOPP recommendations.  Over the course of the study, 41% of the patient population were exposed to a PIM from at least one of the criteria sets.  The 2012 Beers criteria identified PIMs in 34.1% of patients and STOPP identified in 27.6% of patients.  Observed differences are related to differences in classification of inappropriateness between the two identification systems.  The two criteria sets showed similar sensitivity and specificity, although they varied in predictive ability between drug classes, given variation in recommendations between classes of drugs for the two systems.

Both systems displayed acceptable prognostic power to predict adverse drug events in patients exposed to PIMs based on their individual criteria.  The study found no significant differences between the two systems in discrimination power for ADEs or ED visits, although the researchers did admit that further studies would be required to increase the predictive power of the criteria sets by medication classes.  This is the first study of its kind to look into the predictive ability of the major geriatric medication recommendations, and needs further assessment by other groups to get an accurate look at the medication lists for the elderly population in the United States.  What should pharmacists and other health care professionals be looking at to determine if our current recommendations are sufficient?  Do you have any ideas to help ensure the current system of geriatric cares are appropriate?

Article Link

Brown, J. D., Hutchison, L. C., Li, C., Painter, J. T. and Martin, B. C. Predictive Validity of the Beers and Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP) Criteria to Detect Adverse Drug Events, Hospitalizations, and Emergency Department Visits in the United States. Journal of the American Geriatrics Society (2016) 64: 22–30. doi: 10.1111/jgs.13884

Blog Officially Open: Safety of Off-Label Medication Use

Eguale and colleagues conducted a study to monitor and evaluate the off-label use of prescription medications and adverse drug events (ADE) in adults. The authors conducted a prospective cohort study of adult patients who visited a primary care physician in Quebec, Canada who participated in the Medical Office of the XXIst Century (MOXXI) research program and received a prescription for a medication between January 1, 2005 and December 30, 2009. The MOXXI physicians use an electronic health record (EHR) that integrates beneficiary, medical and pharmacy claims information together. The EHR requires that the physician document the indication for the medication, reasons for dose modifications and discontinuations and details related to any ADE. Indications were considered off-label if they were not approved by Health Canada (Canada’s FDA equivalent). A drug information database was used to classify the level of evidence supporting the use of the medications for the off-label indications. Strong evidence was defined as medication effective or favorable efficacy for off-label indication, medication is recommended for most patients with indication, and there are studies of efficacy, including at least one randomized controlled trial. In brief, the study included 46,021 patients who received 151,305 prescriptions of which 11.8% were prescribed off-label. The indication for use was not supported by strong evidence 80.9% of the time. The overall incidence of ADEs for all medications was 13.2 per 10,000 person-months. There was a 44% increase in risk of ADEs when medications were used off-label compared with on-label use. There were higher rates of ADE when the off-label use lacked strong evidence. The authors noted that the elderly and patients who frequent physicians may be overrepresented in their data. The authors concluded that the off-label use of medications is a risk factor for ADE.

JAMA Intern Med. 2016;176(1):55-63

Off-label use of medications is complicated. The editorial that accompanies the Eguale paper discusses some of in the issues, including the potential changes to off-label promotion of medications, the allowance of prescribers to write for off-label medication use, and the lack of surprise of the study’s results. How can EHRs in the US become more sophisticated and user friendly to allow for more clear documentation of off-label use of medications to allow for more thoughtful intervention? How can pharmacists help with the safe and effective use of medications, particularly when off-label use is being considered?