Drug-induced Proarrhythmia and Torsade de Pointes: A Primer for Students and Practitioners of Medicine and Pharmacy.

Multiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety-related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability. ICH Guidelines S7B and E14 were released in 2005. Since then, they have been adopted by many regional regulatory authorities and have guided nonclinical and clinical proarrhythmic cardiac safety assessments during drug development. While this regulatory paradigm has been successful in preventing drugs with unanticipated potential for inducing the rare but potentially fatal polymorphic ventricular arrhythmia torsade de pointes from entering the market, it has led to the termination of drug development programs for other potentially useful medicines because of isolated results from studies with limited predictive value. Research efforts are now exploring alternative approaches to better predict potential proarrhythmic liabilities. For example, in the domain of human electrocardiographic assessments, concentration-response modeling conducted during phase 1 clinical development has recently become an accepted alternate primary methodology to the ICH E14 "thorough QT/QTc" study for defining a drug's corrected QT interval prolongation liability under certain conditions. When a drug's therapeutic benefit is considered important at a public health level but there is also an identified proarrhythmic liability that may result from administration of the single drug in certain individuals and/or drug-drug interactions, marketing approval will be accompanied by appropriate directions in the drug's prescribing information. Health-care professionals in the fields of medicine and pharmacy need to consider the prescribing information in conjunction with individual patients' clinical characteristics and concomitant medications when prescribing and dispensing such drugs.

Clinical pharmacists' opportunities to reduce inappropriate prescription of QT-prolonging medications: calls to action.

All biologically active agents carry the potential to lead to adverse reactions in certain individuals, including serious cardiac adverse reactions. Since 2005, there has been an international regulatory landscape governing the investigation of a new drug's propensity to lead to the polymorphic ventricular tachycardia Torsades de Pointes (Torsades), a rare but potentially fatal occurrence. When a regulatory agency considers it appropriate, warning information is placed in a medicine's patient information leaflet (label) concerning drug-induced QT interval prolongation, a phenomenon associated with Torsades. In busy hospital settings, however, prescribers, including cardiologists, make injudicious prescribing decisions that put patients at risk. The science of cardiac safety, including the clinical trials that generate the information about QT prolongation in patient information leaflets, is frequently not part of the curriculum at Schools of Pharmacy. Given that medication-induced cardiotoxicity is extremely serious, we advocate that schools integrate the science of cardiac safety into existing therapeutics/therapeutic medication monitoring courses. Given their expert knowledge of pharmacology, pharmacists working as part of a hospital's clinical team would then be even better placed to review prescribing decisions concerning medications that prolong the QT interval, and alert prescribers in cases where reassessing their decisions seems prudent. National pharmacy societies or other pertinent professional societies could create practice guidelines to support graduates once employed as clinical pharmacists. Clinical pharmacists are well placed to be influential arbiters of safer prescribing decisions. Cardiac safety education during their pharmacy training and practice guideline support from professional societies during their careers can optimize this role.

Assessment of Postgraduate Year 2 Pharmacy Residency Programs Within the Veterans Affairs Healthcare System.

PURPOSE: Despite the increasing importance placed on advanced training for clinical pharmacists, literature describing postgraduate year 2 (PGY2) residency opportunities is limited. The objective of this study was to describe characteristics of PGY2 programs within the Veterans Affairs (VA) healthcare system. METHODS: An online survey addressing attributes of PGY2 residency programs was electronically distributed to VA residency program directors (RPDs). RESULTS: Responses from 27 (32.9%) VA PGY2 residency programs were included, representing 11 distinct PGY2 specialties. Growth and recruitment trends were similar across programs, with most programs projecting additional expansion. Staffing requirements were uncommon, but opportunities to precept and earn teaching certificates were prevalent. RPDs had been licensed pharmacists an average of 16.9 years, and most had at least 1 advanced certification. The majority of programs had a formal residency advisory committee and required preceptors to attend regular development meetings. CONCLUSION: Although multiple postgraduate specialties were represented, the requirements and opportunities available for PGY2 pharmacy residents were similar across VA facilities. By comparing residency programs in a nationally integrated health-care system, this study may promote growth of existing PGY2 programs, facilitate the establishment of new programs, and provide a framework for prospective residents to evaluate programs of interest.