Assessment of knowledge of the new pregnancy and lactation labeling rule among pharmacists and physicians in Saudi Arabia.

Researchers in Saudi Arabia conducted this study to determine the level of familiarity that pharmacists and physicians possess with the pregnancy and lactation labeling rules established by the Food and Drug Administration. The present study included a cross-sectional survey conducted among pharmacists and physicians working in Saudi Arabia. The sample size was determined using the Rao sample size calculator. We utilized the Statistical Package for the Social Sciences (SPSS) version 25 for our analysis. A total of 122 respondents completed the study. Among them, 72.9% were aged between 25 and 44 years, and approximately 63.9% were male. About 64% of the respondents indicated familiarity with the A, B, C, D, and X letter system of pregnancy category labeling. Over 37% stated that the new pregnancy and lactation labeling rule would continue to use the lettering system. Additionally, 83% believed that the A, B, C, D, and X risk category labeling system is a useful resource, and 82% believed that working with this risk category labeling improves patient care. The study revealed that pharmacists and physicians exhibited good knowledge of the old rule but a low level of knowledge regarding the new rule. Despite significant flaws in the old system, most preferred it. Enhancing knowledge in this area is crucial for improving risk communication and the quality of care for women of reproductive age.

A Perspective on Evaluating Life Stage Differences in Drug Dosages for Drug Labeling and Instructions.

Drug labeling and instructions provide essential information for patients regarding the usage of drugs. Instructions for the dosage of drug usage are critical for the effectiveness of the drug and the safety of patients. The dosage of many drugs varies depending on the patient's age. However, as our understanding of human biology deepens, we believe that these instructions need to be modified to incorporate different life stages. This is because human biology and metabolism differ significantly among different life stages, and their responses to drugs also vary. Additionally, the same age of different persons may fall into different life stages. Therefore, our group from multiple institutes and countries proposes a reexamination of whether incorporating life stages in all or any drug instructions will greatly enhance drug efficiency and patients' health.

Risk of Self-Reported Penicillin Allergy Despite Removal of Penicillin Allergy Label: Secondary Analysis of the PALACE Randomized Clinical Trial.

This secondary analysis of adult patients in the Penicillin Allergy Clinical Decision Rule (PALACE) Study investigates the risk of self-reported penicillin allergy despite removal of penicillin allergy label.

Removing the FDA's Boxed Hepatotoxicity Warning and Liver Function Testing Requirement for Ambrisentan.

Importance: Endothelin receptor antagonists are first-line therapy for pulmonary arterial hypertension (PAH). The first 2 agents approved in the class, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs) as part of a risk evaluation and mitigation strategy (REMS); however, in 2011, as further safety data emerged on ambrisentan, the boxed hepatotoxicity warning and LFT requirements were removed. Objective: To analyze changes in the use of and LFT monitoring for ambrisentan and bosentan after changes to the ambrisentan labeling and REMS. Design, Setting, and Participants: This serial cross-sectional study used data from 3 longitudinal health care insurance claims databases-Medicaid, Optum's deidentified Clinformatics Data Mart, and Merative Marketscan-to perform an interrupted time series analysis of prescription fills and LFTs for patients taking ambrisentan and bosentan. Participants were patients filling prescriptions for ambrisentan and bosentan from July 1, 2007, to December 31, 2018. Data analysis was performed from April 2021 to August 2023. Exposure: Removal of the boxed warning for hepatotoxicity and the REMS LFT monitoring requirements on ambrisentan in March 2011. Main Outcomes and Measures: The primary outcomes were use of ambrisentan (ie, individuals with at least 1 dispensing per 1 000 000 individuals enrolled in the 3 datasets) vs bosentan and LFT monitoring (ie, proportion of initiators with at least 1 ordered test) before initiation and before the first refill. Results: A total of 10 261 patients received a prescription for ambrisentan during the study period (7442 women [72.5%]; mean [SD] age, 52.6 [17.6] years), and 11 159 patients received a prescription for bosentan (7931 women [71.1%]; mean [SD] age, 47.7 [23.7] years). Removal of the ambrisentan boxed hepatotoxicity warning and LFT monitoring requirement was associated with an immediate increase in the use of ambrisentan (1.50 patients per million enrollees; 95% CI, 1.08 to 1.92 patients per million enrollees) but no significant change in the use of bosentan. There were reductions in recorded LFTs before drug initiation (13.1% absolute decrease; 95% CI, -18.2% to -8.0%) and before the first refill (26.4% absolute decrease; 95% CI, -34.4% to -18.5%) of ambrisentan but not bosentan. Conclusions and Relevance: In this serial cross-sectional study of ambrisentan, labeling changes and removal of the REMS-related LFT requirement were associated with shifts in prescribing and testing behavior for ambrisentan but not bosentan. Further clinician education may be needed to maximize the benefits of REMS programs and labeling warnings designed to ensure the safe administration of high-risk medications.

First-line treatment with ceftriaxone for Neisseria gonorrhoeae infection less likely to be prescribed to patients with a penicillin allergy label: a retrospective audit of medical records.

Background Gonorrhoea notifications have increased substantially in Australia over the past decade. Neisseria gonorrhoeae is already highly resistant to several antibiotics and so, alternatives to first-line treatment are generally strongly discouraged. The penicillin allergy label (AL) on patient medical records has previously been shown to influence prescribing practices, to the detriment of best-practice management and antimicrobial stewardship. This study aimed to understand how the penicillin AL influences antibiotic selection for gonorrhoea treatment at Canberra Sexual Health Centre. Methods A retrospective chart audit of gonorrhoea cases treated at Canberra Sexual Health Centre between January 2020 and October 2023 (n =619 patients, n =728 cases). Antibiotic selection was assessed according to penicillin AL status. Ceftriaxone selection was assessed according to penicillin allergy severity reported in the medical records and as determined using a validated antibiotic allergy assessment tool. Results Cases with a penicillin AL were more likely to receive antibiotics other than ceftriaxone (n =7/41, 17.1%) than cases without the label (n =8/687, 1.2%, P n =28/41, 68.3%) to apply the assessment tool. Those reported as low-severity in the records were more likely to receive ceftriaxone (n =21/22, 95.5%) than those reported as moderate-high (n =7/11, 63.6%) or unreported (n =6/8, 0.75%). Conclusions Treatment of gonorrhoea in outpatient settings requires an understanding of penicillin allergy, and the ability to quickly and accurately identify penicillin-AL patients who can safely tolerate ceftriaxone. Institutionally endorsed penicillin allergy de-labelling protocols and access to easy-to-navigate prescribing advice within national sexually transmitted infection management guidelines would support this.

Rational approach to the prescription of anti-rheumatic drugs in rheumatoid arthritis: a product leaflet-based strategy in Italy.

The treatment of patients with rheumatoid arthritis (RA) has dramatically changed in the past 30 years. Currently, numerous conventional, biologic, and targeted synthetic DMARDs have been licensed and used following recommendations provided by international and national scientific societies. However, the availability of biosimilars and the increasing necessity of savings impacted on the local/national prescription of these drugs. The information provided by data sheet of every single drug is a decisive factor on the choice of a certain treatment merged with the patient's profile. Thus, our purpose was to construct a rational algorithm for the treatment strategy in RA according to costs and the product leaflet of the biologic and targeted-synthetic DMARDs currently licensed in Italy. We used the most recent available recommendations and then we performed a review of the literature considering all the factors that are known to influence drug safety/effectiveness. All these factors were considered in the context of the data sheets of currently available originators and biosimilars.

The continuing challenge of drug recalls: Insights from a ten-year FDA data analysis.

In this study we analyzed drug recall data from the U.S. Food and Drug Administration (FDA) over the period 2012-2023. We identified trends in the number of recalls initiated annually and their underlying causes. On average, 330 drug recalls are initiated each year, showing an overall increasing trend. The average duration of a recall, from initiation to termination date, was 1.3 years and each recall involved on average 400 000 product units, implying considerable resource demands and consequences for all stakeholders. The most frequent cause of these recalls was found to be impurities and contaminants (37 %), followed by control (28 %) and labeling/packaging (19 %) issues. Recalls of medicines causing serious health problems or death (class I), accounted for 14 % of the recall events. Continuous evaluation of recalls is expected to reduce their number, mitigate their impact on the healthcare system and improve drug safety.

Age-related off-label drug prescribing in pediatric patients in South Korea and consistency of labeling compared to the United States, Europe, and Japan.

Insufficient labeling information regarding the appropriate age for prescribing drugs to the pediatric population is challenging. This study aimed to analyze the off-label prescription of age-related drugs for pediatric patients using claims data from South Korea and to assess the consistency of the approved age in South Korea, the United States, Europe, and Japan. In 2020, 1004 unique drugs were prescribed to the pediatric population in South Korea. We found that 641 drugs (63.8%, p < 0.0001) were related to off-label prescriptions for age-related use at least once, and the total number of off-label prescriptions was 2,236,669 (62.2%, p < 0.0001). Chlorpheniramine (28%) was the most frequently prescribed drug for pediatric patients with an age-related off-label, followed by budesonide (9%) and epinephrine (9%). The degree of agreement in the approved age range for 641 off-label drugs across countries was assessed using the overall kappa coefficient. We observed slight agreement in labeling across all countries (κ: 0.16, 95% confidence interval [CI]: 0.14-0.18). The highest degree of agreement was observed between the United States and Europe (0.41, 0.37-0.45) due to pediatric-population-specific legislation. South Korea showed the lowest degree of agreement with the United States and Europe (0.10, 0.06-0.14). The United States, Europe, and Japan showed fair agreement (0.23, 0.21-0.26). However, the degree of agreement between South Korea, the United States, and Japan (0.09, 0.06-0.11) and South Korea, Europe, and Japan (0.08, 0.05-0.10) was low. This study highlights the need for South Korean regulatory agencies to consider introducing pediatric legislation to prescribe evidence-based drugs for safe and effective use.

Overdosage Section in US and EU Labeling.

The Prescribing Information (PI) in the United States (US) and the Summary of Product Characteristics (SmPC) in the European Union (EU) are approved by the US Food & Drug Administration (FDA), and the European Medicines Agency (EMA), respectively. The inclusion of overdosage information in these documents is a regulatory requirement in both regions. This research evaluates the content of the overdosage section of US and EU labeling. The overdosage sections of labels for drugs approved in the US in three time periods were analyzed: 2000-2001, 2010-2011, and 2020-2021. EU labels for these same products were also reviewed if registered through the Centralized Procedure. Data collection and analyses were performed using a predefined questionnaire, focusing on adherence to regulatory requirements and identifying areas where additional regulatory guidance may be beneficial. The findings indicate that the content of the overdosage sections largely comply with the regulatory requirements of their respective regions. Fewer than half of the labels included information on supratherapeutic doses observed from clinical studies, risk factors for overdose or population specific data associated with overdose. Inconsistencies were noted concerning the incorporation of animal data when human data were available, in addition to the referencing of Poison Centers. The overall utility of non-specific treatment recommendations, in addition to gastric lavage is discussed. While the content of the overdosage section generally aligns with regulatory expectations, additional regulatory guidance could enhance consistency in how this section of labeling is presented and clarify expectations to improve its usefulness for health care professionals (HCPs).

Testing the amount of nicotinamide mononucleotide and urolithin A as compared to the label claim.

Healthy Longevity Medicine aims to optimize health by targeting aging processes across the lifespan. Addressing accelerated aging involves adaptation of lifestyle and the use of geroprotective drugs and supplements, including nutritional supplements and bioactive compounds. The Food and Drug Administration, under the Dietary Supplement Health and Education Act, categorizes bioactive compounds and medicinal products as dietary supplements. While numerous companies sell ingredients that can be deemed geroprotectors, there's limited oversight in their quality control. Governmental safety authorities only verify the presence of prohibited compounds, not the accuracy of ingredients listed on labels.Here, Nicotinamide mononucleotide and Urolithin A supplements, easily accessible online or in pharmacies, were tested for their active ingredient content. Results showed a significant deviation from the labeled amounts, ranging from + 28.6% to -100%. This indicates a considerable disparity in the quality of geroprotective supplements.To address this variability, collaboration between and within societies representing healthcare professionals, industry and regulatory bodies is imperative to ensure the quality of geroprotective supplements.

Label Accuracy of Legal Oral Cannabis Oil Products in Ontario, Canada.

This case series compares amounts of tetrahydrocannabinol and cannabidiol reported on product labels vs levels found in laboratory testing in legal oral cannabis oil products in Ontario, Canada.

Generic Drugs and the Struggle to Compete: The Role of Skinny Labels.

PURPOSE: The generic drug industry currently faces multiple, serious issues that threaten the US drug supply. So-called "skinny labels" are one of the few tools authorized by Congress to expedite entry into the market by generic competitors when the first patent for a brand's drug compound (only) expires. This article reviews the law on this expedited marketing pathway for generic competitors, as well as limitations on its use. METHODS: We examined the literature on patent protection of brand drugs, including the timelines for production of generic competitors. We also examined the law concerning skinny labels, including a recent decision of the US Federal Circuit Court that clearly articulates the guidelines concerning entry into the generic market, including labeling, marketing, and promotion. FINDINGS: Skinny labels that follow the regulations set forth in the Hatch-Waxman Act, including the necessary carve-out procedure for "methods of use" still protected by 1 or more active patents, do not infringe a brand drug's label. Furthermore, the skinny label does not induce or contribute to infringement merely because its label contains US Food and Drug Administration-required safety profile data-even when the data cross-reference superiority studies on still-patent protected methods of use elsewhere in the label. IMPLICATIONS: Generic drugs have become essential to the broad, general availability of clinical therapeutic agents. The Hatch-Waxman Act was intended to facilitate entry of generic competitors into the marketplace, and the skinny label is an important tool to accomplish that end. As long as the generic manufacturer follows the essential skinny-label rules, specifically including marketing the compound without promoting or advertising those methods of use still protected by ongoing patents, the law will not find induced or contributory infringement.

Hepatotoxicity of Antibiotics and Antifungals and Their Safe Use in Hepatic Impairment.

Idiosyncratic drug-induced liver injury (DILI) is a rare and unpredictable form of hepatotoxicity. While its clinical course is usually benign, cases leading to liver transplantation or death can occur. Based on modern prospective registries, antimicrobials including antibiotics and antifungals are frequently implicated as common causes. Amoxicillin-clavulanate ranks as the most common cause for DILI in the Western World. Although the absolute risk of hepatotoxicity of these agents is low, as their usage is quite high, it is not uncommon for practitioners to encounter liver injury following the initiation of antibiotic or antifungal therapy. In this review article, mechanisms of hepatoxicity are presented. The adverse hepatic effects of well-established antibiotic and antifungal agents are described, including their frequency, severity, and pattern of injury and their HLA risks. We also review the drug labeling and prescription guidance from regulatory bodies, with a focus on individuals with hepatic impairment.