Why Is Oral Phenylephrine on the Market After Compelling Evidence of Its Ineffectiveness as a Decongestant?

Ineffective over-the-counter (OTC) drugs should be removed from the US market. Despite solid research showing that oral phenylephrine is ineffective as a decongestant, the US Food and Drug Administration has failed to respond to a 2015 citizen's petition to remove it from the OTC nasal decongestant monograph. Other examples of scientifically proven ineffective OTC medications include guaifenesin as an expectorant, dextromethorphan as a cough suppressant, and chlorpheniramine for cold symptoms.

Site-Specific and Country-of-Origin Labeling for Pharmaceutical Manufacturing.

There is increasing concern about the quality of pharmaceuticals, especially generics made in Asia. Popular books and news reports have the public questioning the quality of pharmaceuticals. Recalls and import bans shake confidence in medications, particularly for active pharmaceutical ingredients and finished dosage forms made outside the United States. The Food and Drug Administration uses geography to allocate resources for manufacturing surveillance. Site of manufacturing labeling, including the country, could be linked to the facility's quality score to assess the risk of poor quality. Clinicians should advocate for legal and regulatory changes to increase the transparency of pharmaceutical manufacturing of products.

Countries Manufacturing Pharmaceuticals for the US Market: A 10-Year Analysis of Public Data.

BACKGROUND: Concerns about strategic supplies and quality have increased the scrutiny of the countries where US pharmaceuticals are made. OBJECTIVE: To examine the locations of manufacturers of brand name, biological, and generic drugs over 10 years. METHODS: This longitudinal descriptive study used publicly available data from US government Web sites, including the Food and Drug Administration (FDA) Drug Establishments list, FDA National Drug Code Directory, FDA Orange Book, FDA Purple Book, and the National Institutes of Health DailyMed Drug Labels. These data were collected from 2011 to 2020. RESULTS: Brand name drug manufacturing in the United States and Europe decreased from 89% in 2011 to 79% in 2020. Biological manufacturing in the United States decreased, while that in Western European countries increased; 100% of biological manufacturing was done in the United States or Europe in 2011 and decreased to 93% by 2020. Generic manufacturing in India increased from 21% to 51%, while US manufacturing decreased from 52% to 35% from 2011 to 2020. These analyses were limited to publicly available data, and the results could be affected by the accuracy and completeness of the data. CONCLUSIONS AND RELEVANCE: Brand name drugs and biologicals are primarily made in the United States and Europe. Generic drugs are increasingly made in India, but the United States remains a major supplier. If the country of origin for pharmaceuticals is important, these findings support supply chain concerns for generic drugs. We recommend that product containers and official labeling prominently include the manufacturer and location for active pharmaceutical ingredients and finished dosage forms.

Meeting report: an exploration into the scientific and regulatory aspects of pharmaceutical drug quality in the United States.

INTRODUCTION: The University of Florida College of Pharmacy, Department of Pharmaceutical Outcomes and Policy hosted a seminar 6-7 March 2021, on the quality of pharmaceutical products in the United States. This meeting report summarizes the topics presented at the seminar and highlights the expert opinions offered by the presenters. AREAS COVERED: The seminar, held virtually due to the COVID-19 pandemic, included slide presentations and faculty-moderated panel discussions from experts in the field. These experts from regulatory, academic, and private sectors discussed bioequivalence standards, existing and emerging efforts to promote quality in brand and generic manufacturing, as well as market-based solutions throughout the drug supply chain. EXPERT OPINION: The time spent understanding bioequivalence standards during the seminar felt especially important and relevant in our current pandemic environment, given the present need to have confidence in the science of drug development and to advocate for the safety of pharmaceuticals. Also an important point to emphasize from the seminar, was that every stakeholder along the drug supply chain has a responsibility to do their part to maintain its quality. And those in attendance, many of whom were students of healthcare sciences, were encouraged to be leaders in their fields and develop strategies to advance innovative improvements.

Consistency of psychotropic drug-drug interactions listed in drug monographs.

BACKGROUND: With an increasing prevalence of psychotropic polypharmacy, clinicians depend on drug-drug interaction (DDI) references to ensure safe regimens, but the consistency of such information is frequently questioned. OBJECTIVES: To evaluate the consistency of psychotropic DDIs documented in Clinical Pharmacology (CP), Micromedex (MM), and Lexicomp (LC) and summarize consistent psychotropic DDIs. METHODS: In May 2016, we extracted severe or major psychotropic DDIs for 102 psychotropic drugs, including central nervous system (CNS) stimulants, antidepressants, an antimanic agent (lithium), antipsychotics, anticonvulsants, and anxiolytics-sedatives-hypnotics from CP, MM, and LC. We then summarized the psychotropic DDIs that were included in all 3 references and with evidence quality of "excellent" or "good" based on MM. RESULTS: We identified 1496, 938, and 1006 unique severe or major psychotropic DDIs from CP, MM, and LC, respectively. Common adverse effects related to psychotropic DDIs include increased or decreased effectiveness, CNS depression, neurotoxicity, QT prolongation, serotonin syndrome, and multiple adverse effects. Among these interactions, only 371 psychotropic DDIs were documented in all 3 references, 59 of which had "excellent" or "good" quality of evidence based on MM. CONCLUSION: The consistency of psychotropic DDI documentation across CP, MM, and LC is poor. DDI documentations need standards that would encourage consistency among drug information references. The list of the 59 DDIs may be useful in the assessment of psychotropic polypharmacy and highlighting DDI alerts in clinical practice.

Emerging roles for pharmacists in clinical implementation of pharmacogenomics.

Pharmacists are uniquely qualified to play essential roles in the clinical implementation of pharmacogenomics. However, specific responsibilities and resources needed for these roles have not been defined. We describe roles for pharmacists that emerged in the clinical implementation of genotype-guided clopidogrel therapy in the University of Florida Health Personalized Medicine Program, summarize preliminary program results, and discuss education, training, and resources needed to support such programs. Planning for University of Florida Health Personalized Medicine Program began in summer 2011 under leadership of a pharmacist, with clinical launch in June 2012 of a clopidogrel-CYP2C19 pilot project aimed at tailoring antiplatelet therapies for patients undergoing percutaneous coronary intervention and stent placement. More than 1000 patients were genotyped in the pilot project in year 1. Essential pharmacist roles and responsibilities that developed and/or emerged required expertise in pharmacy informatics (development of clinical decision support in the electronic medical record), medication safety, medication-use policies and processes, development of group and individual educational strategies, literature analysis, drug information, database management, patient care in targeted areas, logistical issues in genetic testing and follow-up, research and ethical issues, and clinical precepting. In the first 2 years of the program (1 year planning and 1 year postimplementation), a total of 14 different pharmacists were directly and indirectly involved, with effort levels ranging from a few hours per month, to 25-30% effort for the director and associate director, to nearly full-time for residents. Clinical pharmacists are well positioned to implement clinical pharmacogenomics programs, with expertise in pharmacokinetics, pharmacogenomics, informatics, and patient care. Education, training, and practice-based resources are needed to support these roles and to facilitate the development of financially sustainable pharmacist-led clinical pharmacogenomics practice models.

Complete-block scheduling for advanced pharmacy practice experiences.

PURPOSE: An innovative approach to meeting increased student demand for advanced pharmacy practice experiences (APPEs) is described, including lessons learned during a two-year pilot project. SUMMARY: To achieve more efficient allocation of preceptor resources, the University of Florida College of Pharmacy (UFCOP) adopted a new APPE rotation model in which 20 pharmacy students per year complete all required and elective APPEs at one practice site, an affiliated academic medical center. Relative to the prevailing model of experiential training for Pharm.D. students, the "complete-block scheduling" model offers a number of potential benefits to students, preceptors, and the pharmacy school. In addition to potentially reduced student housing expenses and associated conveniences, complete-block scheduling may enable (1) more efficient use of teaching resources, (2) increased collaboration among preceptors, (3) greater continuity and standardization of educational experiences, and (4) enhanced opportunities for students to engage in longer and more complex research projects. The single-site APPE rotation model also can provide value to the training site by enabling the extension of clinical pharmacy services; for example, UFCOP students perform anticoagulation monitoring and discharge medication counseling at the host institution. Despite logistical and other challenges encountered during pilot testing of the new scheduling model, the program has been well received by students and preceptors alike. CONCLUSION: Complete-block APPE scheduling is a viable model for some health systems to consider as a means of streamlining experiential education practices and helping to ensure high-quality clinical rotations for Pharm.D. students.

Evaluating incorporation of drug restrictions into computerized drug order entries after transition to an electronic health record.

BACKGROUND: Incorporation of drug restriction policy into electronic drug order entries (DOEs) can promote responsible medication use and resource utilization when implemented systematically. OBJECTIVE: To identify drugs that require further incorporation of formulary restriction policy into their DOEs after migration to an electronic health record with computerized prescriber order entry (CPOE). METHODS: After transition to CPOE, test orders for formulary restricted drugs were entered in the CPOE environment. Data were collected about rationale for drug restriction, type of formulary restriction, presence of incorporation of restriction policy into the DOE, and whether incorporation was consistent with a recommended method. Restricted drugs requiring revision of policy incorporation into their DOEs were analyzed to create a prioritized task list based on rationale for the restriction. RESULTS: Of all restricted drugs, 63.6% (287/451) did not have restriction policy incorporated into their DOEs consistent with the recommended method and therefore required revision. Eighteen percent (81/451) of restricted drugs had no incorporation of restriction policy in their DOEs. Safety was the rationale for restriction in 21% (17/81) of these, which received highest priority for revision. When drugs were orderable but restricted, 61.9% (78/126) lacked optimal incorporation of policy in DOEs to promote adherence. When drugs were not orderable, 64% (206/322) did not provide guidance to formulary alternatives in DOEs when they should have. CONCLUSION: After transition to CPOE, almost two-thirds of all analyzed restricted drugs lacked optimal incorporation of formulary restriction policies in their DOEs. DOEs with restrictions related to safety reasons were among those most frequently requiring revision. Some DOEs can better promote adherence and provide guidance to prescribers through revision. Predefined, systematic implementation strategies should be used during changes in computerized drug use processes.

Factors associated with the publication of scholarly articles by pharmacists.

PURPOSE: Factors associated with the publication of scholarly articles by pharmacists were evaluated. METHODS: A Web-based survey was distributed to all pharmacists who published at least one scholarly article in selected pharmacy and medical journals in 2008. All scholarly works published in the American Journal of Health-System Pharmacy, Annals of Pharmacotherapy, and Pharmacotherapy during the study period were categorized by study design using a predetermined algorithm. A secondary group of pharmacists who published in at least 1 of 10 selected medical journals during the study period was also evaluated to identify any differences between those who published in pharmacy versus medical journals. RESULTS: The final number of usable responses was 254, for an adjusted response rate of 72.9%. Factors identified as the most helpful for facilitating publication efforts included time allotment, mentorship, and collaborative efforts. "Lack of time" was reported as the most important barrier to publication. The majority of respondents (73%, n = 182) published their first article during a training program (academic program, residency, or fellowship). Of the 468 scholarly works published in the selected pharmacy journals during the study period, review articles were most common (38.7%, n = 177). CONCLUSION: The most influential factors on the publication efforts by pharmacists were time allotment, collaboration between pharmacy colleagues and within multidisciplinary teams, and training in research methods and scientific writing. Introduction to the publication process during training programs appeared to influence future propensity toward scholarly participation. Review and descriptive articles were the most frequently published types of articles in the pharmacy literature.

Evaluation of contraindicated drug-drug interaction alerts in a hospital setting.

BACKGROUND: Risks associated with contraindicated drug-drug interaction alerts (CDDIAs) should always outweigh benefits. Misclassified CDDIAs should be eliminated. OBJECTIVE: To review CDDIAs and determine if they are contraindicated according to Food and Drug Administration-approved product labeling and if there are circumstances in which contraindicated interactions are acceptable. METHODS: A cross-sectional observational and quality improvement study was conducted over two 1-year periods. The 20 most common CDDIAs from May 2007 to May 2008 and all CDDIAs from April 2008 to April 2009 were collected at a large teaching hospital. Horizon Meds Manager used First DataBank as the knowledge base for decision support. Interactions were deemed truly contraindicated if listed in the contraindications section of the labeling of at least one of the interacting drugs. Alerts were grouped by drug and pharmacologic class to evaluate the evidence supporting the relevance of these interactions. An expert panel determined when an alert was misclassified. A medical advisory committee determined whether a contraindicated drug-drug combination was acceptable. RESULTS: Twelve (60%) of the most common 20 contraindicated interaction pairs from 2007 to 2008 were inappropriately classified. Half of the alerts were not truly contraindicated. The 8 truly contraindicated drug-drug pairs were ketorolac and other nonsteroidal antiinflammatory drugs or oral solid potassium products and anticholinergics. Half of these interactions were subsequently deemed acceptable under specific circumstances. Similar results were found in the second year, with only 55.1% of all CDDIAs being truly contraindicated despite eliminating some of the alerts that were misclassified in the first year. Nearly three fourths of legitimate CDDIAs were deemed acceptable under specific circumstances. CONCLUSIONS: Most contraindicated drug-drug interaction alerts from a commercial knowledge base were inappropriately categorized and could be downgraded. Some contraindicated drug combinations are permissible under specific circumstances. Alerts suggesting that certain drugs should never be used together, but their use together is sometimes acceptable, contribute to alert fatigue.

Pharmacy resident project publication rates and study designs from 1981, 1991, and 2001.

PURPOSE: The publication rates and characteristics of residency projects presented at the Southeastern Residency Conference (SERC) in 1981, 1991, and 2001 are described. METHODS: SERC abstracts from 1981, 1991, and 2001 were searched in MEDLINE and International Pharmaceutical Abstracts with a time limit of six years after the conference. All potential positive publications were reviewed and validated by a second investigator. Publication rates and other secondary variables, including study design, authors' degrees, reporting of results, time to publication, and journal of publication, were compared, with differences noted. RESULTS: A total of 272 abstracts were evaluated. Publication in a journal was achieved for 18 (20%) of 90 projects presented in 1981, 11 (16%) of 70 projects presented in 1991, and 14 (13%) of 112 projects presented in 2001. The median time to publication for all abstracts was 22.8 months. Publications rates decreased at each subsequent time period. Projects published in journals with high impact factors had a longer median time to publication compared with other projects. Abstracts that reported results were published more often than those that did not (43% versus 23%), as were those that included a physician coauthor compared with those that did not (32% versus 19%). Observational studies were the most common study designs and were most published. CONCLUSION: Approximately 16% of pharmacy residents' research projects presented at SERC in 1981, 1991, and 2001 were published. Projects with observational study designs were the most common study type and were the most commonly published.

Evaluation of seven i.v. drug compatibility references by using requests from a drug information center.

PURPOSE: The scope of coverage and clinical performance of i.v. drug compatibility references were evaluated for drug pairs. METHODS: Compatibility pairs were selected from a drug information center database of previous questions. Duplicate pairs, contrast media, and nondrug chemicals were excluded. Scope of coverage was defined as whether i.v. compatibility information was present for each pair and was reported as a percentage. Clinical performance included the agreement among the references on compatibility, the inclusion of specific concentration information for each drug in a pair, and the presence of references for the information provided. The analysis included one print reference (Handbook on Injectable Drugs, 14th edition) and six electronic i.v. drug compatibility references (King Guide to Parenteral Admixtures, Trissel's 2 Clinical Pharmaceutics Database, Micromedex's IV INDEX, Gold Standard's Clinical Pharmacology, Facts and Comparisons 4.0 IV Chek, and CompoundingToday.com). The manufacturers' online labeling was also consulted. RESULTS: A total of 97 unique drug pairs were analyzed. Four databases contained i.v. compatibility information on 76% of the drug pairs, one contained 62%, one contained 58%, one contained 56%, and the manufacturers' labeling contained 13% of the pairs. Seventy-nine percent of the pairs had agreement among the references as to whether the pair was compatible, incompatible, or variable. Compounding Today.com, Facts and Comparisons IV Chek, the Handbook on Injectable Drugs, IV INDEX, and Trissel's 2 reported concentrations and references for the information given on all pairs. CONCLUSION: The highest-performing references included in the evaluation used the compatibility information provided in Trissel's 2 database as their source of information. Other popular references identified fewer pairs, and the manufacturers' labeling rarely contained compatibility information.

Effects of concomitant amiodarone and haloperidol on Q-Tc interval prolongation.

PURPOSE: The effects of concomitant amiodarone and haloperidol on Q-Tc interval prolongation were studied. METHODS: All adult patients admitted to a 618-bed tertiary referral teaching hospital between January 1, 2005, and December 31, 2006, who received amiodarone and haloperidol concomitantly were included in this retrospective descriptive analysis. Data collected to assess patients' risk of developing Q-T interval prolongation included age, sex, past medical history, and number of days of concomitant exposure. Data relevant for the assessment of cardiac effects were collected for the time period between 24 hours before and after the administration of haloperidol and included laboratory test values, use of other Q-T interval-prolonging drugs, heart rate, Q-Tc intervals, and clinical documentation of arrhythmia. To determine change in the Q-Tc interval, Q-T and R-R values were recorded using cardiac rhythm strips or electrocardiogram. Nurses' and physicians' records were reviewed to determine if an arrhythmia occurred. Descriptive statistics were used to analyze baseline patient information and Q-Tc interval data. RESULTS: A total of 49 patients met inclusion criteria, yielding 381 distinct amiodarone-haloperidol exposures. During 138 (36.2%) of 381 haloperidol-amiodarone exposures, patients received at least one additional Q-T interval-prolonging drug. When amiodarone-haloperidol exposures were grouped by the number of concomitant Q-T prolonging drugs, no apparent association was detected between longer Q-Tc intervals and an increased number of concomitant Q-T interval-prolonging drugs. CONCLUSION: A small, potentially significant Q-Tc interval prolongation, but not ventricular arrhythmia, was observed in adult patients who received a concomitant administration of amiodarone and haloperidol at a tertiary referral teaching hospital.

An evaluation of the effects of gatifloxacin on glucose homeostasis.

INTRODUCTION: The United States labeling for gatifloxacin has been updated to include contradictions related to its reported association with dysglycemia. However, adequately controlled studies in acute care settings assessing the magnitude and clinical determinants of dysglycemia are lacking. OBJECTIVES: To compare the hypoglycemic and hyperglycemic effects of gatifloxacin with ceftriaxone in hospitalized patients. METHODS: A retrospective cohort study of hospitalized adult (> or =18 years) patients admitted with Community Acquired Pneumonia (CAP) or Acute Exacerbation of Chronic Bronchitis (AECB) in a US tertiary care hospital between 7/1/01 and 12/31/04 treated with gatifloxacin or ceftriaxone during hospital admission. Outcomes of interests were incidence of hypoglycemia (blood glucose levels <46 mg/dL) or hyperglycemia (>200 mg/dL) during up to 5 days of drug exposure. Risks for gatifloxacin and ceftriaxone were compared adjusting for variables previously reported to be independent predictors of hypoglycemia or hyperglycemia. RESULTS: 1504 patients met the study inclusion criteria. Compared to ceftriaxone, gatifloxacin was associated with an increased risk of hypoglycemia: (adjusted odds ratio (OR) 2.34, 95% confidence interval (CI) 1.4-4.0). The increased risk of hypoglycemia during exposure to gatifloxacin was similar in patients with and without a diagnosis of diabetes mellitus. Gatifloxacin was not associated with an increased risk for hyperglycemia (adjusted OR: 1.06 95% CI 0.8-1.4) considering the whole study cohort. However, stratification by diagnosis of diabetes, gatifloxacin treated patients appeared to have a reduced risk of hyperglycemia (adjusted OR: 0.4 95% CI 0.2-0.4) while non-diabetic gatifloxacin treated patients appeared to have an increased risk of hyperglycemia (adjusted OR: 1.64 95% CI 1.1-2.4). CONCLUSION: The risk of dysglycemia with gatifloxacin in this population of hospitalized patients was not as high as previously reported in ambulatory patients. Although these results suggest gatifloxacin use is safer in acute care settings, we recommend that clinicians monitor blood glucose levels carefully or consider alternatives to gatifloxacin therapy whenever possible.