Análise das solicitações de medicamentos não padronizados de um hospital universitário terciário / Analysis of requests for non-standard medicines from a tertiary university hospital

Introdução: O uso extensivo de medicamentos não padronizados causa aumento de custos em saúde, além de potencial redução de segurança e uso racional de medicamentos. A Comissão de Farmácia e Terapêutica orienta a prescrição de medicamentos, por meio da avaliação e seleção de medicamentos a serem incluídos no formulário de medicamentos padronizados, com base nas melhores evidências científicas disponíveis e no perfil dos pacientes locais, promovendo o uso racional de medicamentos. O objetivo deste trabalho foi analisar as solicitações de fornecimento de medicamentos não padronizados na instituição. Métodos: Trata-se de um estudo observacional e descritivo onde foram analisadas as solicitações de medicamentos não padronizados realizadas entre fevereiro de 2016 e dezembro de 2021, identificando os medicamentos envolvidos e seus respectivos custos. Resultados: Foram realizadas 203 solicitações no período, sendo 174 incluídas no estudo. Os medicamentos que tiveram mais solicitações foram o rituximabe (41), a imunoglobulina humana (31), o sucralfato (23), a nitazoxanida (12) e o eltrombopague (7). As solicitações com maior custo foram as de imunoglobulina humana (US$ 799,702.38), rituximabe (US$ 717,320.26), eltrombopague (US$ 281,062.50), ruxolitinibe (US$ 167,867.46) e bortezomibe (US$ 149,033.52). As principais clínicas que solicitaram medicamentos não padronizado foram a neurologia (47), a hematologia (30), as moléstias infecciosas e parasitárias (17), e a anestesiologia (12). As solicitações de maior custo foram realizadas pela neurologia (US$ 145,519.08), hematologia (US$ 120,980.25), transplante de medula óssea (US$ 51,635.11) e dermatologia (US$ 44,813.40). Conclusão: O estudo demonstrou que há um fluxo estruturado de solicitação de medicamentos não padronizados na instituição, sendo uma importante ferramenta de gerenciamento dessas solicitações, evitando a aquisição desnecessária de itens que não compõem o elenco terapêutico do hospital.

Introduction: Widespread use of non-formulary drugs (NFD) increases cost and may reduce safety and rational use of medicines. The Pharmacy and Therapeutics Committee provides guidance on drug prescription by evaluating and selecting medications to be included in a hospital's formulary based on best scientific evidence available and local patients' profile, promoting rational use of medicines. The objective of this study was to assess non-formulary drugs prescriptions at a tertiary hospital. Methods: This was a retrospective study. NFD prescribed and its associated costs were assessed through NFD request forms received from February 2016 to December 2021. Results: A total of 203 NFD request forms were received, from which 174 were included in this study. The most frequently prescribed NFD included rituximab (n = 41), immunoglobulin (31), sucralfate (23), nitazoxanide (12), and eltrombopag (7), with the highest costs being with immunoglobulin (US$ 799,702.38), rituximab (US$ 717,320.26), eltrombopag (US$ 281,062.50), ruxolitinib (US$ 167,867.46), and bortezomib (US$ 149,033.52). The most frequent requesting specialties were neurology (n = 47), hematology (30), infectious disease (17) and anesthesiology (12), and highest costs requests were from neurology (US$ 145,519.08), hematology (US$ 120,980.25), bone marrow transplant unit (US$ 51,635.11), and dermatology (US$ 44,813.40). Conclusion: This study showed that a structured request flow for NFD prescription is a critical procedure in order to better manage drug prescription within the hospital, promoting rational use of medicines and preventing unnecessary spending with drugs for which the clinical indication may be covered by a drug already in the hospital's formulary.

Government Mandated Consent Dramatically Reduces Pediatric Urologist Opioid Utilization for Outpatient and Minor Emergency Surgeries.

PURPOSE: Postoperative opioids are overprescribed in the United States. In November 2016 the State of Pennsylvania required an opioid consent for minors. Our hypothesis is that this mandate decreased postoperative opioid prescriptions in our division. MATERIALS AND METHODS: All patients who received a urological outpatient or minor emergency procedure from August 2015 to August 2019 were identified. Surgeries performed within 6 months after mandate implementation were excluded to account for the transition period. Perioperative data including case type were extracted by a clinical data warehouse from preexisting fields within the health record. The frequencies of postoperative prescriptions, delayed prescriptions and emergency department encounters were assessed. A multivariable logistic regression to identify predictors of opioid prescription at discharge was performed. RESULTS: A total of 4,349 patients were analyzed. The frequency of postsurgical opioid prescriptions decreased from 45.3% to 2.6% (p <0.001). The median morphine milligram equivalent decreased by 22.5 among children prescribed an opioid (p <0.001). Rates of an emergency department visits (3% vs 2.7%) or delayed nonopioid prescriptions (0.8% vs 1.2%) within 30 days of discharge were unchanged (p >0.05). Fewer patients received a delayed opioid prescription after mandate implementation (0.03% vs 0.5%, p <0.001). Female patients were less likely (OR 0.309, 95% CI 0.195-0.491; p <0.001) to receive opioids prior to but not after the mandate (OR 0.309, 95% CI 0.544-2.035; p=0.122). Increasing age was predictive of receiving an opioid before (OR 1.187, 95% CI 1.157-1.218; p <0.001) and after (OR 1.241, 95% CI 1.186-1.299; p <0.001) the mandate. CONCLUSIONS: A state mandated opioid consent for minors greatly reduced post-urological surgery opioid prescription rates without increasing rates of readmission or delayed prescriptions.

Effects of State Law Limiting Postoperative Opioid Prescription in Patients After Cesarean Delivery.

BACKGROUND: The impact of the Florida State law House Bill 21 (HB 21) restricting the duration of opioid prescriptions for acute pain in patients after cesarean delivery is unknown. Our objective was to assess the association of the passage of Florida State law HB 21 with trends in discharge opioid prescription practices following cesarean delivery, necessity for additional opioid prescriptions, and emergency department visits at a large tertiary care center. METHODS: This was a retrospective cohort study conducted at a large, public hospital. The 2 cohorts represented the period before and after implementation of the law. Using a confounder-adjusted segmented regression analysis of an interrupted time series, we evaluated the association between HB 21 and trends in the proportions of patients receiving opioids on discharge, duration of opioid prescriptions, total opioid dose prescribed, and daily opioid dose prescribed. We also compared the need for additional opioid prescriptions within 30 days of discharge and the prevalence of emergency department visits within 7 days after discharge. RESULTS: Eight months after implementation of HB 21, the mean duration of opioid prescriptions decreased by 2.9 days (95% confidence interval [CI], 5.2-0.5) and the mean total opioid dose decreased by 20.1 morphine milligram equivalents (MME; 95% CI, 4-36.3). However, there was no change in the proportion of patients receiving discharge opioids (95% CI of difference, -0.1 to 0.16) or in the mean daily opioid dose (mean difference, 5.3 MME; 95% CI, -13 to 2.4). After implementation of the law, there were no changes in the proportion of patients who required additional opioid prescriptions (2.1% vs 2.3%; 95% CI of difference, -1.2 to 1.5) or in the prevalence of emergency department visits (2.4% vs 2.2%; 95% CI of difference, -1.6 to 1.1). CONCLUSIONS: Implementation of Florida Law HB 21 was associated with a lower total prescribed opioid dose and a shorter duration of therapy at the time of hospital discharge following cesarean delivery. These reductions were not associated with the need for additional opioid prescriptions or emergency department visits.

The role of school characteristics in pre-legalization cannabis use change among Canadian youth: implications for policy and harm reduction.

Reducing youth cannabis use in Canada is a public health priority with schools of interest as a potential modifier of behavior and as a venue for prevention programming. This work aimed to provide a basis for future policy and programming by evaluating pre-legalization cannabis use change patterns in schools and the impact of school characteristics on these patterns. Average rates of cannabis use behavior change (initiation, escalation, reduction, cessation) were collected from 88 high schools located in Ontario and Alberta, Canada participating in the COMPASS prospective cohort study. There was little variability in cannabis use behaviors between schools with intra-class correlation coefficients lowest for cessation (0.02) and escalation (0.02) followed by initiation (0.03) and reduction (0.05). Modest differences were found based on school province, urbanicity and student-peer use. Cannabis ease of access rates had no significant effect. Fewer than half the schools reported offering school drug use prevention programs; these were not significantly associated with student cannabis use behaviors. In conclusion, current school-based cannabis prevention efforts do not appear sufficiently effective. Comprehensive implementation of universal prevention programs may reduce cannabis harms. Some factors (urbanicity, peer use rates) may indicate which schools to prioritize.

How do state Medicaid programs determine what substance use disorder treatment medications need prior authorization? An overview for clinicians.

The process by which state Medicaid programs develop their preferred drug lists, and determine which medications require prior authorization, is opaque to many clinicians. This process is a synthesis of cost and clinical information. For cost, the federal Medicaid Drug Rebate Program establishes mandatory rebates that pharmaceutical manufacturers must pay state Medicaid programs. In addition, state Medicaid programs may also negotiate supplemental rebates whereby, in exchange for a preferred position on the preferred drug list, manufacturers pay an additional rebate. These supplemental rebates are most important in therapeutic classes with multiple brand competitors (e.g., medication treatments for opioid use disorder). For clinical information, state Medicaid programs convene pharmaceutical and therapeutics committees, drug utilization review boards, or both, composed of a variety of stakeholders such as practicing clinicians. Cost factors such as federal rebate calculations and supplemental rebate negotiations may lead to counterintuitive preferred drug lists, for example, a state Medicaid program requiring prior authorization for a generic medication but not for its brand equivalent (e.g., buprenorphine/naloxone products). Because of states' reliance on rebates, mandates to remove prior authorization may have the unintended consequence of increasing costs significantly through the loss of rebate negotiating power. In the face of high and rising medication costs, state Medicaid programs are also implementing innovative policy approaches to maintain access and control costs, such as targeted rebate negotiation and value-based pricing. Through participation in state Medicaid program clinical advisory committees, individual clinicians can have a powerful voice. Interested clinicians should consider joining to inform policy and help ensure their patients' needs are met.

[Present Conditions of Marijuana Regulation in USA: Medical and Recreational Use].

In most countries marijuana is regulated by the Single Convention on Narcotic Drugs. In Japan marijuana use is illegal under the Marijuana Control Law. In USA, marijuana is also classified as a schedule I drug, which is the most stringent regulation category under federal law. On the other hand, California became the first state to legalize marijuana for medical uses in 1996. Since then, several other US states have approved marijuana for medical or recreational use. However, marijuana remains completely illegal in most states, while some allow only cannabidiol (CBD) extracted from marijuana for medical use. In June 2018, the US Food and Drug Administration approved Epidiolex, the first marijuana-derived drug, containing purified CBD, to treat certain rare childhood seizure syndromes. Therefore the situation surrounding control of marijuana in USA is complex. Recently, a definite trend toward reconsidering marijuana regulation has been seen around the world, which could have a major impact on marijuana policy in Japan. In this review, we investigated existing medical and recreational marijuana laws in various US states, with a focus on California, which approved recreational use in 2018. Here, we describe the current state of marijuana regulation in terms of both medical and recreational use. In addition, we discuss public safety issues associated with marijuana, including crime, traffic accidents, and emergency department visits from possible marijuana exposure, as well as generated tax revenues, from official marijuana-related reports in Colorado, which legalized marijuana use in 2012.

Pharmaceutical policies: effects of educational or regulatory policies targeting prescribers.

BACKGROUND: Pharmaceuticals make an important contribution to people's health. Medicines, however, are frequently not used appropriately. Improving the use of medicines can improve health outcomes and save resources. On the other hand, regulatory and educational policies may have unintended effects on health and costs. OBJECTIVES: To assess the effects of pharmaceutical educational and regulatory policies targeting prescribers on medicine use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries in March 2018 and several other databases between 2014 and 2018. We reviewed the reference lists of included studies and other relevant reviews, contacted authors of relevant reviews and studies to identify additional studies, and did a citation search for all included studies using ISI Web of Science (searched 05 January 2016). SELECTION CRITERIA: Randomised trials, non-randomised trials, interrupted time series studies, repeated measures studies and controlled before‒after studies of policies regulating who can prescribe medicines and other policies targeted at prescribers. We included in this category monitoring and enforcement of restrictions, generic prescribing, programmes to implement treatment guidelines, system-wide policies regarding monitoring medicine safety, and legislated or mandatory continuing education or quality improvement specifically targeted at prescribing. We defined 'policies' in this review as laws, rules, financial and administrative orders made by governments, non-governmental organisations or private insurers. We excluded interventions applied at the level of a single facility. For us to include a study, it had to include an objective measure of at least one of the following outcomes: medicine use, healthcare utilization, health outcomes, or costs. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and reference lists of relevant reports, assessed full-text studies for inclusion, extracted data, and assessed risk of bias and certainty of the evidence (GRADE). For all the steps in the above process we resolved disagreements by discussion. MAIN RESULTS: We identified two studies that met our selection criteria: a controlled interrupted time series study evaluating a regulatory policy involving the monitoring of prescribing of benzodiazepines; and a controlled before‒after study of an educational policing involving mailed educational materials on prescribing for physicians and Health Maintenance Organization (HMO) members as well as an intervention to regulate drug reimbursement. We are uncertain about the effects on medicine use of a regulatory policy involving the monitoring of prescribing with triplicate prescriptions, compared with no regulatory intervention (very low certainty evidence). We are also uncertain about the effects on medicine use, assessed through doctors' prescribing, and costs of an educational policy involving mailed educational materials on prescribing for physicians and HMO members, compared to no educational intervention or an intervention to regulate drug reimbursement (very low certainty evidence). Neither of the included studies measured healthcare utilization, health outcomes, or additional costs, if any, to patients. AUTHORS' CONCLUSIONS: We are uncertain of the effects of educational or regulatory policies targeting prescribers due to very limited evidence of very low certainty. The impacts of these policies therefore need to be evaluated rigorously using appropriate study designs. Evaluations are needed across a range of settings, including low- and middle-income countries, and across different types of prescribers and medicines.

[Evolution of the legal and normative framework surrounding the practice of hospital pharmacy and the correct use of drugs in Quebec]. / Évolution du cadre juridique et normatif entourant l'exercice de la pharmacie hospitalière et le bon usage des médicaments au Québec.

OBJECTIVES: The objective was to identify the main texts applicable to the practice of pharmacy in Quebec, then count the specific number of recommendations and criteria and describe the evolution of the legal and normative framework. METHODS: This is a descriptive and retrospective study of the main texts applicable to the legal and normative framework for the practice of pharmacy on January 1st, 2019. RESULTS: A total of 107 texts relating to the practice of pharmacy in Quebec were identified. They come from the legislator (53.1 %), the Order of pharmacists (26.1 %) or other organizations (20.8 %). These were laws/regulations (n=59), contributing to the optimal use of drugs (n=18), relating to hospital pharmacy management (n=18), the provision of pharmaceutical care (n=11), drug preparation (n=3), oncology practice (n=2) or health and safety at work (n=1). Thirty-three texts were considered for enumeration of recommendations and explicit criteria, for a total of 235 recommendations and 3703 explicit criteria applicable to the practice of hospital pharmacy in Quebec. CONCLUSION: There is a significant increase in the number of texts, recommendations and criteria applicable to the practice of hospital pharmacy in Quebec. Compliance with this legal and normative framework appears to be a considerable challenge for hospital pharmacists. It seems worthwhile to further promote discussion with text-issuing agencies in order to keep the search for compliance realistic.

Restrictive measure for the commercialization of antimicrobials in Brazil: results achieved.

OBJECTIVE: To assess whether the incidence of hospital infection by a resistant microorganism decreased after the implementation of the restrictive measure of the National Health Surveillance Agency for the commercialization of antimicrobials. METHODS: A historical cohort study of medical records of adult patients admitted to a general and public hospital from May 2010 to July 2011. A cohort was formed with patients admitted in the period before the restrictive measure for the commercialization of antimicrobials (Phase I) and a second cohort was formed with patients admitted after the implementation of the restrictive measure (Phase II). RESULTS: The instantaneous risk of hospital infection by a resistant microorganism was estimated at seven by 1,000 people-time (95%CI 0.006-0.008) in Phase I, and four by 1,000 people-time (95%CI 0.003-0.005) in Phase II of the study. The differences between the survival curves in the different phases of the study and stratified by age group were also significant (p < 0.05). CONCLUSIONS: The results suggest that the implementation of the restrictive measure of the commercialization of antimicrobials by the National Health Surveillance Agency reduced the incidence of hospital infection by a resistant microorganism.

Opioid prescribing in minimally injured trauma patients: Effect of a state prescribing limit.

BACKGROUND: Opioid-prescribing practices for minimally injured trauma patients are unknown. We hypothesized that opioid-prescribing frequency and morphine-equivalent doses prescribed have decreased in recent years, specifically surrounding an acute prescribing limit implemented in August 2017 mandating opioid prescriptions not exceed 210 morphine-equivalent doses. METHODS: A single-center retrospective study was performed in the month of May during the years 2015 to 2018 on minimally injured trauma patients in a level I trauma center. Minimally injured trauma patients included patients discharged within 2 midnights of trauma evaluation without surgical intervention. Primary outcomes were discharge opioid-prescribing frequency and dosing in morphine-equivalent doses. Secondary outcomes were occurrence and timing of postdischarge follow-up. RESULTS: For 673 minimally injured trauma patients, opioid-prescribing frequency and morphine-equivalent doses prescribed decreased between 2015 and 2017 (49.3% to 31.5%, P = .006, mean 229 to 146 morphine-equivalent doses, P = .007). Decreases between 2017 and 2018 were not statistically significant. Acute prescribing limit compliance was 97% in 2018. After the acute prescribing limit was implemented, outpatient opioid prescribing did not increase and time to earliest follow-up did not decrease. CONCLUSION: Opioid-prescribing frequency and morphine-equivalent doses prescribed to minimally injured trauma patients decreased dramatically between 2015 and 2018. These changes occurred primarily before the implementation of an acute prescribing limit; however, incremental improvement and high compliance since implementation are demonstrated. Patients did not have significantly earlier follow-up encounters for pain or additional opioid prescriptions. Prospective research on pain control for minimally injured trauma patients is needed.

Mandatory Prescription Limits and Opioid Utilization Following Orthopaedic Surgery.

BACKGROUND: Since 2016, over half of the states in the United States have passed mandatory limits on opioid prescriptions, with limited evidence of effectiveness. In this study, we evaluated postoperative opioid prescriptions following orthopaedic surgery before and after the implementation of one of the earliest such laws. METHODS: Following the implementation of state legislation limiting opioid prescriptions for opioid-naïve patients, 2 patient cohorts (pre-law and post-law) were compared. Both opioid-tolerant and opioid-naïve patients undergoing 6 common orthopaedic procedures (total knee arthroplasty, rotator cuff repair, anterior cruciate ligament reconstruction, open reduction and internal fixation for a distal radial fracture, open reduction and internal fixation for an ankle fracture, and lumbar discectomy) met inclusion criteria. Patients undergoing >1 primary procedure in the same operative session were excluded. All benzodiazepine and opioid prescriptions from 30 days before to 90 days after the surgical procedure were recorded. Logistic regression was performed to determine risk factors for prolonged postoperative opioid use. RESULTS: In this study, 836 pre-law patients were compared with 940 post-law patients. The 2 groups were similar with regard to demographic variables, baseline opioid tolerance, and recent benzodiazepine use (all p > 0.05). Post-law, for all patients, there were decreases in the initial prescription pill quantity (49.65 pills pre-law and 22.08 pills post-law; p < 0.001) and the total morphine milligram equivalents (MMEs) (417.67 MMEs pre-law and 173.86 MMEs post-law; p < 0.001), regardless of patient preoperative opioid exposure (all p < 0.001). Additionally, there were decreases in the mean cumulative 30-day MMEs (790.01 MMEs pre-law and 524.61 MMEs post-law; p < 0.001) and the 30 to 90-day MMEs (243.51 MMEs pre-law and 208.54 MMEs post-law; p = 0.008). Despite being specifically exempted from the legislation, opioid-tolerant patients likewise experienced a significant decrease in cumulative 30-day MMEs (1,304.08 MMEs pre-law and 1,015.19 MMEs post-law; p = 0.0016). Opioid-tolerant patients required more postoperative opioids at all time points and had an increased likelihood of prolonged opioid use compared with those who were opioid-naïve preoperatively (odds ratio, 8.73 [95% confidence interval, 6.21 to 12.29]). CONCLUSIONS: A clinically important and significant reduction in opioid utilization after orthopaedic surgery was observed following the implementation of statewide mandatory opioid prescription limits. CLINICAL RELEVANCE: After implementation of mandatory opioid prescription regulations, a clinically important and significant decline in the volume of opioids dispensed in the short term and intermediate term following orthopaedic surgery was observed. Furthermore, important clinical predictors of prolonged postoperative opioid use, including preoperative opioid use and preoperative benzodiazepine use, were identified. These findings have important implications for public health, as well as the potential to influence policymakers and to change practice among orthopaedic surgeons.

The Impact of Increased Hydrocodone Regulation on Opioid Prescribing in an Urban Safety-Net Health Care System.

BACKGROUND: Hydrocodone-combination analgesics were changed from Schedule III to Schedule II to discourage the prescribing of these analgesics. Our primary aim was to explore the effect of hydrocodone rescheduling on opioid prescribing within an urban safety-net health care system. METHODS AND DESIGN: Data were extracted from electronic records of ambulatory patients (N = 82,432 patients) prescribed hydrocodone-combination, codeine-combination, or tramadol opioid analgesics (N = 200,675 prescriptions) between October 6, 2013 and October 6, 2015. Data analyses modeled predicted probabilities of hydrocodone-combination prescriptions (HCPs). Chronic opioid therapy (COT) for chronic pain (ie, ≥3 opioid prescriptions/12 months) and morphine milligram equivalency (MME) levels were also examined. RESULTS: The probability of providers writing HCPs decreased significantly from pre- to postrescheduling (0.525 vs 0.158, respectively, P < .0001). However, this coincided with large probability increases in codeine-combination (0.064 vs 0.269) and tramadol prescriptions (0.412 vs 0.573). The probability of HCPs varied across physician specialty (P < .0001), patient diagnoses (P < .0001), COT versus non-COT patients (P < .0001), and patient characteristics (sex, race/ethnicity, and age; P < .05). COT patients received significantly more opioid prescriptions in the postrescheduling period (M = 4.81 vs M = 4.27; P < .0001). Patients on <20 MME/day increased slightly from pre- to postrescheduling (P < .0001). DISCUSSION: Significant declines in HCPs occurred after rescheduling; however, one third of patients prescribed opioids remained on doses ≥20 MME/day. Codeine- and tramadol-prescription probabilities increased significantly and providers may have an increased perception of safety about these medications. Physicians and health care systems must reduce their overreliance on opioids in treating pain, especially chronic pain, as all opioids incur some level of risk.

The effectiveness of formulary restriction and preauthorization at an academic medical center.

The impact of formulary restriction and preauthorization (FRPA) on prescribing trends was examined over a 5-year period at an academic medical center. Ordinary least squares regression was used to identify hospital units demonstrating statistically significant trends in prescription of restricted agents. Significant decreases in restricted drug use were seen on 2 of 7 medicine units subject to FRPA, whereas a significant increase was seen in 1 of 4 surgical units subject to FRPA.