DALES, Drug Allergy Labels in Elective Surgical patients: a prospective, multicentre cross-sectional study of prevalence, nature and anaesthetists' approach to management.

BACKGROUND: We sought to define the prevalence and nature of patient-reported drug allergies, determine their impact on prescribing, and explore drug allergy knowledge and attitudes amongst anaesthetists. METHODS: We performed a prospective cross-sectional study in 213 UK hospitals in 2018. Elective surgical patients were interviewed, with a detailed allergy history taken in those self-reporting drug allergy. Anaesthetists completed a questionnaire concerning perioperative drug allergy. RESULTS: Of 21 219 patients included, 6214 (29.3 %) (95% confidence interval [CI]: 28.7-29.9) reported drug allergy. Antibiotics, NSAIDs, and opioids were the most frequently implicated agents. Of a total of 8755 reactions, 2462 (28.1%) (95% CI: 29.2-31.1) were categorised as high risk for representing genuine allergy after risk stratification. A history suggestive of chronic spontaneous urticaria significantly increased the risk of reporting drug allergy (odds ratio 2.68; 95% CI: 2.4-3; P<0.01). Of 4756 anaesthetists completing the questionnaire, 1473 (31%) (95% CI: 29.7-32.3) routinely discuss perioperative allergy risk with patients. Prescribing habits in the presence of drug allergy labels differ depending on the implicated agent. Most anaesthetists (4678/4697; 99.6%) (95% CI: 99.4-99.8) prescribe opioids when reactions are consistent with side-effects, although 2269/4697 (48%) (95% CI: 46.9-49.7) would avoid the specific opioid reported. CONCLUSIONS: Almost 30% of UK elective surgical patients report a history of drug allergies, but the majority of reported reactions are likely to be non-allergic reactions. Allergy labels can impact on perioperative prescribing through avoidance of important drugs and use of less effective alternatives. We highlight important knowledge gaps about drug allergy amongst anaesthetists, and the need for improved education around allergy.

Why are certain age bands used for children in paediatric studies of medicines?

Rational prescribing of medicines requires evidence from clinical trials on efficacy, safety and the dose to be prescribed, based on clinical trials. Regulatory authorities assess these data and information is included in the approved summary of product characteristics. Regulatory guidelines on clinical investigation of medicinal products in the paediatric population generally propose that studies are done in defined age groups but advise that any classification of the paediatric population into age categories is to some extent arbitrary or that the age groups are intended only as a guide. The pharmaceutical companies tend to plan their studies using age groups the regulatory guidelines suggest, to avoid problems when applying for marketing authorisation. These age bands end up in the paediatric label, and consequently into national paediatric formularies. The age bands of the most commonly used age-subsets: neonates, infant/toddlers, children and adolescents, are more historical than based on physiology or normal development of children. Particularly problematic are the age bands for neonates and adolescents. The age of 12 years separating children from adolescents, and the upper limit of the adolescents set by the definition of paediatric age in healthcare, which varies according to the region, are particularly questionable. Modern pharmacometric methods (modelling and simulation) are being increasingly used in paediatric drug development and may allow assessment of growth and/or development as continuous covariables. Maybe time has come to reconsider the rational of the currently used age bands.

Current Challenges in Labelling for Generic Medicinal Products: Company Core Data Sheet (CCDS) Development and Maintenance.

Labelling of pharmaceutical products plays a vital role in the safe and effective use of approved medicinal products. This information may be provided to end-users including patients and/or prescribers, and it needs to be made available in multiple formats including printed forms (patient information leaflets, pack inserts, etc.) or web portals of the product, based on national authority guidelines. The Company Core Data Sheet (CCDS) serves as a key document representing the pharmaceutical company's position on the product and is used as a reference document for national labels. Content from national labels may differ from the CCDS for different reasons including implementation of national authority requirements in the serving market and findings from local markets. In the current article, we discuss the process, challenges and key concepts in creating and maintaining CCDS documents for generic products. We highlight key parameters that are worthy of process improvement in generic products' CCDS updates. In addition, we argue that labelling harmonisation across multiple regions, especially safety section-related information, plays a key role in promoting end-user safety and would help communicate risks. We also strongly believe that the topic is worthy of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) consideration, and propose that this is the key area that requires standardisation and harmonisation.

FDA postmarketing safety labeling changes: What have we learned since 2010 about impacts on prescribing rates, drug utilization, and treatment outcomes.

PURPOSE: Prior literature reviews have identified gaps in understanding of how postmarketing safety labeling changes and related FDA communications impact key clinical and behavioral outcomes. We conducted a review of newly published studies on this topic to determine what new evidence exists and to identify which gaps may still remain. We believe that this information can support FDA as it develops and implements future risk communication approaches. METHODS: We searched PubMed and Embase for studies published between January 1, 2010, and August 7, 2017 that examined the impact of labeling changes or associated FDA safety-related communications. For each study, we extracted information on research design and findings for key clinical outcomes and behaviors. We also conducted a ROBINS-I review to identify potential for bias in the research design of each study. RESULTS: We found that the estimated impacts of FDA labeling changes on several key outcomes-including adverse events-varied. Labeling changes also yielded unintended consequences on drug prescribing in some cases, despite low provider adherence. Finally, some studies we reviewed exhibited potential for bias due to confounding, among other factors. CONCLUSIONS: The new studies we reviewed contain many of the same limitations identified in previously published reviews. While there are several challenges to conducting this research there is substantial room for improvement in the quality of the evidence base. More information, particularly with respect to the types of populations and medications affected by labeling changes, is needed to support the development of more effective and targeted safety communications.

Drug identification by the patient: Perception of patients, physicians and pharmacists.

INTRODUCTION: Faced with the increasing number of pharmaceutical products on the market, several pharmacovigilance notifications regarding confusion between look-alike and sound-alike drugs have been reported. This study of perception among patients, family physicians and pharmacists aims to evaluate drug identification factors and the risk of errors of confusion for patients. MATERIAL AND METHODS: Patients were systematically approached in randomly selected pharmacies within the Midi-Pyrénées region in France and invited to complete a questionnaire. Two other questionnaires were respectively sent to family physicians and pharmacists in the same region asking for their opinion on patients' perception of the identification of prescribed medicines. RESULTS: Of the 768 patients interviewed, most report identifying their medications by name (brand name: 50%; generic: 21%), while a smaller number cite physical appearance (box: 16%, tablet: 7% and blister packaging: 3%). In practice the factors considered most likely to cause confusion by patients relate to drug appearance (look-alike tablets: 28%, look-alike boxes: 20% and look-alike blister packaging: 13%). In contrast, look-alike and sound-alike names (generic and brand names combined) were cited in 31% of cases. Physicians (n=345) and pharmacists (n=198) understimate that patients identify their treatment by name (physicians: 46%; pharmacists: 26% vs. patients: 71%), reporting instead that problems arise mainly from the appearance of medicines (physicians: identification: 52% and risk factors for confusion: 74%; pharmacists: identification: 74% and risk factors for confusion: 83%; versus patients: identification: 26%; risk factors for confusion: 61%). DISCUSSION: Our study highlights the critical role of medication name in identifying drugs among patients. However, confusion of look-alike tablets or pills figures prominently among fears surrounding medication errors. Despite several notifications of pharmacovigilance, this issue appears to be underestimated within the body of medical literature. Proper identification of medicines by patients is essential to improving medication safety and therapeutic compliance. Concrete measures can be undertaken to reach this goal.

Assessing provider and racial/ethnic variation in response to the FDA antidepressant box warning.

INTRODUCTION: After the 2004 FDA box warning raised concerns about increased suicidal ideation among youth taking antidepressants, antidepressant use decreased for White youth but slightly increased for Black and Latino youth. Better understanding of patient and provider factors contributing to these differences is needed to improve future risk warning dissemination. METHODS: We analyzed antidepressant prescriptions for youth aged 5-17 in 2002-2006 Medicaid claims data from four states (CA, FL, NC, and NY). In multilevel models, we assessed provider- and patient-level contributions to changes in antidepressant use by race/ethnicity and compared responses to the box warning between providers with large (>2/3) and small (<1/3) proportions of minority patients. RESULTS: A significant amount of variance in overall prescribing patterns (calculated by the ICC) was explained at the provider level. Significant provider-level variation was also identified in the differential effect of the box warning by racial/ethnic group. In a test of the influence of provider panel mix, we found that providers with large proportions of minority patients reduced antidepressant prescribing more slowly after the box warning than other providers. DISCUSSION: This study is the first to assess provider- and patient-level variation in the impact of a health care policy change on treatment disparities. Black and Latino youth Medicaid beneficiaries were seen by largely different providers than their White counterparts, and these distinct providers were influential in driving antidepressant prescription patterns following the box warning. Concerted outreach to providers of minority beneficiaries is needed to ensure that risk warnings and clinical innovations diffuse swiftly across racial/ethnic minority groups.

Completion Rate and Reporting of Mandatory Pediatric Postmarketing Studies Under the US Pediatric Research Equity Act.

Importance: Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies. Objective: To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act. Design and Setting: A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications. Main Outcomes and Measures: Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models. Results: Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information. Conclusions and Relevance: Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.

Pharmacogenomic biomarkers: Interpretation of information included in United States and Japanese drug labels.

WHAT IS KNOWN AND OBJECTIVES: Many drug labels contain information on pharmacogenomic biomarkers (PGBMs), but the information is not necessarily actionable. Pharmacogenomics Knowledgebase (PharmGKB) aims to clarify the level of action for PGBMs (PGx levels) implied in each label as issued by the US Food and Drug Administration. We wished to evaluate the association between the PGx level for US and Japanese drug labels and the insurance coverage for PGBM testing or approval for in vitro diagnostics (IVDs) in each country. METHODS: We investigated the information on PGBMs in US and Japanese drug labels with PGx levels, insurance coverage of PGBM tests and IVD approval in the US and Japan. We analysed the relationship of PGx levels with insurance coverage. RESULTS: A total of 243 labels were listed by PharmGKB, and 215 (88%) had PGx levels for US labels and 52 (21%) for Japanese labels. Of the 215 US labels, 54 were designated as "Testing Required" in PGx levels. PGx levels in US labels were strongly associated with coverage of PGBM testing. Tests in 52 (96%) of the 54 labels with Testing Required had insurance coverage, 2 (50%) of 4 in "Testing Recommended," 38 (38%) of 100 in "Actionable PGx," 11 (19%) of 57 in "Informative PGx" and 3 (11%) of 28 in "No Level." In Japanese labels, only 14 of 52 were listed as Testing Required, and all were covered by the National Health Insurance in Japan. WHAT IS NEW AND CONCLUSION: The PGx level given in drug labels provides information on availability of PGBM testing. Higher PGx levels, based on better evidence of usefulness of PGBM testing, provide a route to broader test coverage.

Assessment of self-reporting reading of medicine's labels and the resources of information about medicines in general public in Malaysia.

This study was undertaken to assess the people's self-reported reading of medicine labels and its associated factors and to assess the sources of information about medicines among general public. A cross-sectional study was carried out among general public in the State of Penang, Malaysia. A total of 888 participants were conveniently selected and completed the survey. A self-administered questionnaire was used to obtain the data from all the participants. Most of the participants (74.2%) reported that they have adequate information about medicines provided on their medicine labels. In addition, 86.9% of them reported that they read their medicine's label for the directions of usage and 84.3% for the dosage instruction. However, 42.1% of the participants do not read their medicine's label for the active ingredients, and 33% of them do not read their medicine's label for the safety information. In addition, 36.5% of the respondents did not read the label of medicine for the symptoms which can be used for. However, females, Malay respondents, and higher education level (college/university) were more likely to self-reported the reading medicine's label. Females were more likely to read the labels of medicines compared with males (OR = 1.6, 95% CI 1.20-2.13, P = .001). The reading of medicine labels was predicted by females, Malay respondents, and higher educated people. Health educational programs are needed to clarify label's information that can help in concept of patient safety.

Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome.

Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction ( P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.

Unintended Consequences of Adjusting Citalopram Prescriptions Following the 2011 FDA Warning.

OBJECTIVES: In 2011, the U.S. Food and Drug Administration (FDA) issued a safety announcement cautioning providers against prescribing citalopram above 40 mg per day given concerns for QT prolongation. We assessed the impact of a health system quality improvement initiative to identify patients taking higher than the recommended dose of citalopram. DESIGN: Retrospective cohort study. SETTING: Nine primary care clinics within the University of Michigan from March 2012 to February 2013. PARTICIPANTS: Adult patients taking a higher-than-recommended dose of citalopram following the FDA warning in 2011 (N = 199). MEASUREMENTS: Frequency of EKG monitoring, clinical factors associated with patients whose citalopram dose or use was adjusted, and potential impact of these changes on overall health care utilization was assessed. RESULTS: In patients prescribed higher-than-recommended doses of citalopram and who received a note from a pharmacist regarding the FDA warnings, only 8.5% received electrocardiogram (EKG) monitoring. Patients who were converted to an alternative antidepressant from citalopram were more likely to receive subsequent new prescriptions for benzodiazepines and sedative hypnotics (χ2 = 7.9, p = 0.048). Patients who had any adjustments to their antidepressant medication had greater overall health care utilization (OR: 25.0; 95% CI: 5.7-109.6; p < 0.001) than patients remaining on the same dose of citalopram. CONCLUSIONS: Despite a targeted quality intervention to address the FDA warning regarding citalopram, the warning was associated with low levels of EKG monitoring, increased anxiolytic and sedative medication use, and higher healthcare utilization. This finding may represent destabilization of patients on previously therapeutic doses of their antidepressant and an unintended consequence of the FDA warning.

Assessment of drug use patterns in terms of the WHO patient-care and facility indicators at four hospitals in Southern Ethiopia: a cross-sectional study.

BACKGROUND: Patient-centered care is now the goal for virtually all healthcare systems. The aim of this research was to evaluate the patient care quality in regard to drug dispensing in four hospitals in southern Ethiopia namely Wolaita Sodo University teaching and referral hospital (WSUTRH), Tercha zonal hospital (TZH), Sodo Christian hospital (SCH) and Dubo St. Mary's Catholic primary hospital (DSMCPH). METHODS: A cross sectional study was conducted by using the WHO patient care and facility indicators between September 10 and October 20, 2014. Patients who visited the outpatient departments of the four hospitals were selected by systematic random sampling method and interviewed. In total 384 patients were selected based on a rough estimate of proportion of patients visiting to the four hospitals. Facility indicators including the availability of essential drugs list (EDL), national drug formulary, standard treatment guideline (STG) and key drugs were evaluated. Descriptive statistical calculations were performed using SPSS® version 20.0 software. RESULT: The mean number of drugs was in the range between 1.9 ± 0.9 to 2.2 ± 2.0. The mean consultation time range was found to be 4.2 ± 1.6 to 4.9 ± 5.0 min whereas the mean dispensing time was ranged from 96.1 ± 52.0 to 152.3 ± 47.6 s. The overall mean number of drug prescribed for the four hospitals was 2.0 ± 1.2 and the mean percentage of medications actually dispensed in the hospitals was thus calculated to be 86.3. The mean percentage of medications clearly labeled was 45.4. Patients who knew their dosage forms accurately were 78.8. Among the four hospitals evaluated only one hospital (25 %) had at least a copy of the Ethiopian essential drug list (EDL), standard treatment guideline for hospitals and drug formulary. The mean availability of key drugs in the hospitals was found to be 65.7 %. CONCLUSION: The result of the present study indicates that the patient consulting time, medications labeling and availability of key drugs in the hospitals are inadequate. The medication labeling practice in the four hospitals is unacceptably low. These patient care indicators need a special attention for improvement.

Searches for randomized controlled trials of drugs in MEDLINE and EMBASE using only generic drug names compared with searches applied in current practice in systematic reviews.

BACKGROUND: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation of informative systematic reviews (SRs). METHODS: We conducted a retrospective analysis of relevant references included in SRs of drugs. We determined the proportion of references identified by a simplified technique consisting of a systematic search for RCTs in MEDLINE and EMBASE via the search interface Ovid and using only the truncated generic drug name in all search fields. We calculated aggregated sensitivity and also evaluated the unidentified references. RESULTS: Forty-eight SRs contained 873 primary publications, of which we found 829 in MEDLINE and 757 in EMBASE ("gold standard"). The simplified search identified 823 of the 829 MEDLINE references (sensitivity 99.3%) and 754 of the 757 EMBASE references (99.6%). Ultimately, only three references could not be found by additional searches. CONCLUSION: Our findings indicate that when searching for RCTs of drugs in MEDLINE and EMBASE, a search using the truncated generic drug name in all fields produces sufficient results.

Readability assessment of package inserts of biological medicinal products from the European medicines agency website.

BACKGROUND: Package inserts that accompany medicines are a common source of information aimed at patients and should match patient abilities in terms of readability. OBJECTIVE: Our objective was to determine the degree of readability of the package inserts for biological medicinal products commercially available in 2007 and compare them with the readability of the same package inserts in 2010. METHODS: A total of 33 package inserts were selected and classified into five groups according to the type of medicine: monoclonal antibody-based products, cytokines, therapeutic enzymes, recombinant blood factors and other blood-related products, and recombinant hormones. The package inserts were downloaded from the European Medicines Agency website in 2007 and 2010. Readability was evaluated for the entire text of five of the six sections of the package inserts and for the 'Annex' when there was one. Three readability formulas were used: SMOG (Simple Measure of Gobbledygook) grade, Flesh-Kincaid grade level, and Szigriszt's perspicuity index. RESULTS: No significant differences were found between the readability results for the 2007 package inserts and those from 2010 according to any of the three readability indices studied (p>0.05). However, there were significant differences (p<0.05) between the readability scores of the sections of the package inserts in both 2007 and 2010. The readability of the package inserts was above the recommended sixth grade reading level (ages 11-12) and may lead to difficulties of understanding for people with limited literacy. CONCLUSIONS: All the sections should be easy to read and, therefore, the readability of the medicine package inserts studied should be improved.

Assessment of PRO label claims granted by the FDA as compared to the EMA (2006-2010).

BACKGROUND: The US Food and Drug Administration (FDA) provides formal guidance for the use of patient-reported outcomes (PROs) in support of labeling claims, whereas the European Medicines Agency (EMA) offers insight in a reflection paper relating to health-related quality of life in lieu of formal guidance. OBJECTIVES: PRO label claims granted for new molecular entities and biologic license applications from 2006 through 2010 were reviewed to evaluate consistencies and discrepancies in PRO label claims granted by the FDA and the EMA and to highlight trends in the acceptance of PRO claims across agencies. METHODS: Products approved by both the FDA and the EMA were identified. By using US Drug Approval Packages and European Public Assessment Reports packages, any PRO label claims made for the same product by the same company were compared. RESULTS: Both agencies approved a total of 75 products. Of these, 35 (47%) had at least one EMA-granted PRO label claim compared with 14 (19%) by the FDA. Most FDA-grated claims focused on symptoms; however, EMA-granted claims were more likely to include higher order concepts. Few (~12%) were granted the same label claims. Despite this discordance between the two agencies, where PRO label claims were granted by both the FDA and the EMA, there was similarity in the type of label claim. CONCLUSIONS: The EMA is more likely than the FDA to grant PRO claims and for higher order constructs. On a macro level, there appears to be poor concordance between claims granted by both agencies. On close examination, however, there appears to be greater concordance than previously recognized, which may be instructive in formulating future PRO strategies. Further research to create strategic alignment across agencies may be beneficial.

Outcomes associated with concordance of oral antidiabetic drug treatments to prescribing information in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVES: This retrospective study aims to examine the association between prescribing information (PI)-concordant oral antidiabetic drug (OAD) treatment and clinical and economic outcomes in patients with type 2 diabetes mellitus and stages 3-5 chronic kidney disease (CKD). METHODS: The study used a large, national administrative claims database with laboratory findings to identify patients with a diagnosis of diabetes and indication of stages 3-5 CKD (first observed indication as the index date) between 1/1/2005 and 30/06/2009. OADs prescribed during 6 months following the index date (baseline period) were evaluated and patients were considered non-PI-concordant if any did not meet the recommendations regarding patients with renal impairment. Glycemic control and measures of healthcare costs (standardized to 2010 US dollars using the Consumer Price Index) and resource utilization were assessed during the 12 months following the baseline period. Severe hypoglycemic events were assessed after the baseline period until lost to follow-up. Regression analyses were performed after adjusting for demographic and clinical characteristics. RESULTS: Among the 3300 patients included in the study, 2454 (74.4%) were non-PI-concordant. The non-PI-concordant patients had higher risk of severe hypoglycemic events identified in all settings (HR = 1.35, 95% CI: 1.10-1.67) and events identified in inpatient hospital setting (HR = 2.51, 95% CI: 1.49-4.22), were more likely to have inpatient hospital admissions (OR = 1.27, 95% CI: 1.02-1.57), and were less likely to have glycemic control (OR = 0.56, 95% CI: 0.44-0.71). Annual diabetes-related cost was $1638 higher in the non-PI-concordant cohort (p = 0.0048). LIMITATION: The retrospective cohort design does not allow for conclusions to be drawn on the causal effect of PI-concordant use based on the associations observed. CONCLUSION: Our findings suggest PI-concordant treatment to be associated with better clinical and diabetes-associated economic outcomes. Future research is warranted to confirm the associations found in this study.

Storage and wastage of drug products in Jordanian households: a cross-sectional survey.

OBJECTIVE: Appropriate household storage and use of drug products can reduce drug wastage and unnecessary hazards. We aimed to quantify the amounts and types of medications that were stored in Jordanian households and the extent of drug wastage in terms of the amount and cost of these medications. METHODS: The setting was households in Amman, Jordan. This was a cross-sectional survey study using a pre-piloted questionnaire. Family members were interviewed in person about use of drug products, and where drug products were stored. The main outcomes were types, storage methods, cost and quantities of drug products in every household. KEY FINDINGS: Two hundred and forty-three households were approached, out of which 219 agreed to participate. A total of 2393 (mean 10.9, SD 5.2) drug products were recorded from the 219 households surveyed. A significant positive correlation was noted between the number of drug products in a household and family size (r = 0.19, P < 0.01), the level of the mother's education (r = 0.24, P < 0.01), the level of the father's education (r = 0.28, P < 0.01) and income (r = 0.14, P = 0.034). Eighty nine (40.6%) households had at least one child younger than 6 years of age, and 1122 (46.9%) drug products were stored in unsafe places in the houses, within the reach of children. More than a quarter of drug products (1509, 27.2%) were not in their original containers, 360 (15%) were unused since dispensing, 261 (10.9%) had expired and 44 (1.8%) had no clear expiry date. We estimated that the cost of drug wastage in the 219 households was US$5414. Paracetamol (202, 8.4%), diclofenac (98, 4.1%) and amoxicillin (79, 3.3%) were the most commonly reportedly stored individual drugs. CONCLUSION: Drug products are stored in large quantities in Jordanian households. Unsafe storage practices have the potential to pose safety hazards, especially to children.

Pattern of extemporaneous prescriptions and preparations in a tertiary health institution: a five-year assessment.

Due to the increasing rate in the demand of extemporaneous formulations, it became necessary to assess the pattern of prescription and preparation in a developing institution. The purpose of this study was to assess the pattern of extemporaneous prescription and preparation in the University of Benin Teaching Hospital, Benin City, Nigeria. Records of prescription and preparation of extemporaneous formulations were assessed retrospectively between 2007 and 2011. Fifty-nine different types of drugs were prescribed with a frequency of 6,882 times during the period. These were indicated for eight classes of systemic disease. Eighteen drugs were indicated for central nervous diseases, followed by 16 drugs for cardiovascular diseases. Of the 18 drugs indicated for central nervous diseases, pyridoxine was the most common. Rifampicin for tuberculosis was the most frequently formulated, followed by spironolactone for cardiovascular disorders. Most preparations were labeled to be used for a maximum of two weeks. They were all liquid preparations packaged in amber-colored bottles. Distilled water was the most common vehicle utilized for trituration; while ascorbic acid syrup was commonly used to bulk the solution and as a sweetening agent. None of the patients reported with any form of pharmaceutical degradation or toxicity within two weeks of expected use. There were reports of spillages due to poor handling. Maximum volume prepared was 75 mL. The study suggests an adequate setup of a quality-control unit in the institution to meet the increasing demand for specific agents. This will enhance an effective healthcare delivery among patients.

Health literacy assessment of labeling of pediatric nonprescription medications: examination of characteristics that may impair parent understanding.

OBJECTIVE: Poor quality and variability of medication labeling have been cited as key contributors to medication misuse. We assessed the format and content of labels and materials packaged with common pediatric liquid nonprescription medications. METHODS: Descriptive study. A total of 200 top-selling pediatric oral liquid nonprescription medications (during the 52 weeks ending October 30, 2009) categorized as analgesic, cough/cold, allergy, and gastrointestinal products, with dosing information for children <12 years (representing 99% of U.S. market for these products) were reviewed. The principal display panel (PDP) and FDA Drug Facts panel (side panel) of each bottle, and associated box, if present, were independently examined by 2 abstractors. Outcome measures were content and format of active ingredient information and dosing instructions of the principal display panel and Drug Facts panel. RESULTS: Although almost all products listed active ingredients on the Drug Facts panel (side panel), nearly 1 in 5 (37 [18.5%]) did not list active ingredients on the PDP. When present, mean (SD) font size for PDP active ingredients was 10.7 (5.0), smaller than product brand name (32.1 [15.0]) and flavor (13.1 [4.8]); P < .001. Most products included directions in chart form (bottle: 167 [83.5%], box: 148 [96.1%], P < .001); mean (SD) font size: 5.5 (0.9; bottle), 6.5 (0.5; box), P < .001. Few products expressed dosing instructions in pictographic form: 4 (2.6%) boxes and 0 bottles. Nearly all products included the Food and Drug Administration-mandated sections. CONCLUSIONS: The format and content of labels for nonprescription pediatric liquid medications could be improved to facilitate parent understanding of key medication information, including active ingredient information and dosing instructions.

Age-related changes in antidepressant pharmacokinetics and potential drug-drug interactions: a comparison of evidence-based literature and package insert information.

BACKGROUND: Antidepressants are among the most commonly prescribed psychotropic agents for older patients. Little is known about the best source of pharmacotherapy information to consult about key factors necessary to safely prescribe these medications to older patients. OBJECTIVE: The objective of this study was to synthesize and contrast information in the package insert (PI) with information found in the scientific literature about age-related changes of antidepressants in systemic clearance and potential pharmacokinetic drug-drug interactions (DDIs). METHODS: A comprehensive search of two databases (MEDLINE and EMBASE from January 1, 1975 to September 30, 2011) with the use of a combination of search terms (antidepressants, pharmacokinetics, and drug interactions) was conducted to identify relevant English language articles. This information was independently reviewed by two researchers and synthesized into tables. These same two researchers examined the most up-to-date PIs for the 26 agents available at the time of the study to abstract quantitative information about age-related decline in systemic clearance and potential DDIs. The agreement between the two information sources was tested with κ statistics. RESULTS: The literature reported age-related clearance changes for 13 antidepressants, whereas the PIs only had evidence about 4 antidepressants (κ < 0.4). Similarly, the literature identified 45 medications that could potentially interact with a specific antidepressant, whereas the PIs only provided evidence about 12 potential medication-antidepressant DDIs (κ < 0.4). CONCLUSION: The evidence-based literature compared with PIs is the most complete pharmacotherapy information source about both age-related clearance changes and pharmacokinetic DDIs with antidepressants. Future rigorously designed observational studies are needed to examine the combined risk of antidepressants with age-related decline in clearance and potential DDIs on important health outcomes such as falls and fractures in older patients.