MANAGEMENT OF RISKS OF ADVERSE DRUG REACTIONS ACCORDING TO ADR REPORT FORM DATA FROM LVIV REGION HEALTHCARE FACILITIES IN 2022.

The study aimed to analyse the adverse drug reactions report form data received by the State Expert Center of the Ministry of Health of Ukraine from healthcare professionals in the Lviv region in 2022. Regarding specific types of medicines, the ones with proven cause-and-effect relationships that caused the highest frequency of adverse drug reactions incidents were chemotherapeutic agents (35.5%), medicines affecting the cardiovascular system (20.3%), and non-steroidal anti-inflammatory drugs (8%). Within the penicillin class, amoxicillin potentiated by clavulanate (67%) and amoxicillin (29%) were the dominant drugs showing the highest incidence rate of adverse reactions. Among cephalosporins, ceftriaxone (46%) and cefixime (15%) were found to take the lead in terms of adverse reaction frequency. The highest proportion among all adverse drug reactions caused by penicillins and cephalosporins was attributed to allergic reactions. To confirm or rule out immediate or delayed type allergies in patients, as well as in patients with a history of immediate-type allergic reactions to ß-lactams and planned administration of another ß-lactam, it is necessary to conduct skin testing (skin prick test, or, in the case of parenteral administration, intradermal test) with the planned ß-lactam antibiotic. The second highest proportion of induced adverse drug reactions was attributed to drugs affecting the cardiovascular system (20.3%). The leading medications in the angiotensin-converting enzyme inhibitors category were enalapril (47%) and the combination of lisinopril with hydrochlorothiazide (24%). In the angiotensin II receptor blockers category of medications, valsartan (30%) and telmisartan-hydrochlorothiazide combination (20%) ranked highest. In the category of CCB drugs, amlodipine (66%) and nifedipine (20%) held the leading positions. among angiotensin-converting enzyme inhibitors, enalapril caused the most prevalent and predicted adverse reaction, that of cough, affecting 10.5% of patients, whereas, with the combination therapy of lisinopril and hydrochlorothiazide, the cough was observed in only 5.2% of patients. Angiotensin II receptor blockers have a better safety profile, particularly concerning cough. Analysis of adverse drug reactions reports for angiotensin II receptor blockers showed no cases of cough with valsartan and telmisartan-hydrochlorothiazide combination. Among calcium channel blocker medications, amlodipine emerged to rank highest, causing one of the predicted adverse drug reactions, that of lower extremity oedema in 64% of patients. The second position was taken by the combination of amlodipine with valsartan, which showed a statistically significant reduction of 14.3% (p≤0.05) in the incidence of oedema. Using amlodipine at a dose of 5 mg in combination with sartan medicines as angiotensin receptor blockers is an effective therapeutic alternative not only for enhancing blood pressure control in hypertensive patients but also for improving the safety profile of amlodipine. Among all the non-steroidal anti-inflammatory drugs prescribed to patients in the Lviv region in 2022, the highest number of adverse reactions was associated with the administration of diclofenac, ibuprofen, paracetamol, and nimesulide, causing adverse drug reactions in 22%, 19%, 17%, and 10% of cases, respectively. The most common systemic manifestations of adverse reactions with these non-steroidal anti-inflammatory drugs were allergic reactions (63.4%) and gastrointestinal disorders (26.8%). From an evidence-based medicine perspective, the most justified approach for primary and secondary prevention of gastrointestinal complications is the use of proton pump inhibitors.

Tramadol utilization among patients with higher risk of adverse drug events: A claims analysis of commercially insured and Medicare Advantage members.

OBJECTIVE: To assess prescribing of tramadol among patients with contraindications and higher risks of adverse events in a large population of commercially insured and Medicare Advantage members. DESIGN: We performed a cross-sectional analysis evaluating tramadol utilization in patients with higher risk of adverse outcomes. SETTING: This study utilized 2016-2017 data from the Optum Clinformatics Data Mart. PATIENTS AND PARTICIPANTS: Patients with at least one tramadol prescription without a cancer or sickle cell diagnosis during the study period. MAIN OUTCOME MEASURES: We first determined if tramadol was prescribed among patients with contraindications or risk factors for adverse outcomes. We then determined if patient demographic or clinical factors were associated with the use of tramadol in these higher-risk scenarios using multivariable logistic regression models. RESULTS: Among patients with at least one prescription for tramadol, 19.66 percent (99 percent CI: 19.57-19.75) concurrently received an interacting cytochrome P450 isoenzyme medication, 19.24 percent (99 percent CI: 19.15-19.33) concurrently received a serotonergic medication, and 7.93 percent (99 percent CI: 7.88-8.00) concurrently received a benzodiazepine. Additionally, 1.59 percent (99 percent CI: 1.56-1.61) of patients who received tramadol also had a seizure disorder, while 0.55 percent (99 percent CI: 0.53-0.56) of patients were under the age of 18. Overall, nearly one in three patients (31.17 percent) received tramadol in the presence of at least one of these risks (99 percent CI: 31.06-31.27). CONCLUSION: Almost one in three patients prescribed tramadol had a clinically significant drug interaction or contraindication for use, suggesting that prescribers often disregard these concerns. Real-world studies are needed to better understand the likelihood of harms associated with the use of tramadol in these contexts.

Side Effects of Antihypertensives Induced by Switching to Different Generic Medications: Case Reports.

Generic medication is a product that contains the same active substance and pharmaceutical characteristics as brand-name medications. Generic medications are cost-effective and comparable to brand-name medications in terms of clinical endpoints. However, the use of generic medications instead of brand-name medications is a debatable issue among patients and healthcare providers. Two patients with essential hypertension experienced side effects after switching to different generic antihypertensives (one generic medication to another generic medication). Adverse drug reactions, including, hypersensitivity, side effects, and intolerance, should be identified through present and past medical history and clinical characteristics. The adverse drug reactions in both patients were more likely to be side effects of the medications after switching to different generic antihypertensives produced by different companies (patient 1: enalapril and patient 2: amlodipine). The side effects were possibly caused by the different inactive ingredients or excipients. These two case reports emphasise the importance of monitoring adverse drug reactions throughout the course of treatment and communicating with patients prior to switching to a new generic medication.

Implications of Under-Reporting Medication Side Effects: Beta-Blockers in Heart Failure as a Case Example.

INTRODUCTION: Perceiving medication side effects but not reporting them to a clinician is common. Patterns of "under-reporting" and their implications are not well described. We aimed to address this gap by examining patterns of under-reporting perceived side effects of beta-blockers among patients with heart failure. METHODS: In 2016, a survey that evaluated medication-taking behavior was administered to 1114 participants (46.5% response rate) from The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with prior adjudicated heart failure hospitalization or a heart failure Medicare claim. We examined the results of survey respondents who reported taking a beta-blocker to understand patterns of under-reporting perceived beta-blocker side effects. We defined an under-reporter as a participant who perceived experiencing a side effect from their beta-blocker but did not share it with their clinician (according to survey responses). We conducted a multivariable logistic regression analysis to identify determinants of being an under-reporter. Co-variates included age, sex, race, income, level of education, geographical location, and pill burden. We also examined whether under-reporters differed in self-reported medication adherence and willingness to take additional medication to prevent a future healthcare encounter compared to participants who reported perceived side effects to their clinicians and those who did not experience side effects. RESULTS: Among 310 respondents, 28% (n = 87) were under-reporters. Black race (odds ratio 2.11, confidence interval 1.21-3.67) and education less than college (odds ratio 2.00, confidence interval 1.09-3.67) were associated with being an under-reporter. Self-reported medication adherence was similar between groups (under-reporters: 46.3%; those who reported perceived side effects: 49.4%; those who did not experience side effects: 45.0%); under-reporters were more frequently unwilling to take additional medication to prevent a doctor's visit (18.9% vs 12.1% vs 10.8%), emergency room visit (21.6% vs 13.3% vs 9.9%), and hospitalization (17.6% vs 10.8% vs 9.0%) compared with the other groups. CONCLUSION: We conclude that under-reporting perceived side effects of beta-blockers among adults with heart failure is common, is associated with Black race and low education, and may contribute to patient willingness to take additional medication to prevent future medical encounters.

Clinical and economic impact of clinical oncology pharmacy in cancer patients receiving injectable anticancer treatments: a systematic review.

PURPOSE: Clinical pharmacy can reduce drug-related iatrogenesis by improving the management of adverse effects of drugs, limiting drug-drug interactions, and improving patient adherence. Given the vulnerability of cancer patients and the toxicity of injectable anticancer drugs, clinical pharmacy service (CPS) could provide a significant clinical benefit in cancer care. This review aims to synthesize existing evidence on clinical pharmacy's impact on patients treated with intravenous anticancer drugs. METHODS: A comprehensive search was performed in the PubMed/Medline database from January 2000 to December 2021, associating the keywords: clinical pharmacy, pharmaceutical care, pharmacist, oncology, and chemotherapy. To be eligible for inclusion, studies have to report clinical pharmaceutical services for patients treated with intravenous chemotherapy with a clinical and/or economic impact. RESULTS: Forty-one studies met the selection criteria. Various CPS were reported: medication reconciliation, medication review, and pharmaceutical interview with patient. There was a lack of randomized study (n = 3; 7.3%). In one randomized controlled trial, pharmaceutical intervention significantly improved quality of life of patients receiving pharmaceutical care during injectable anticancer drugs courses. Economical results appear to show positive impact of clinical pharmacy with cost savings reported from 3112.87$ to 249 844€. Although most studies were non-comparative, they highlighted that clinical pharmacy tend to limit chemotherapy side effects and drug-related problems, improve quality of life and satisfaction of patients and healthcare professional, and a positive economic impact. CONCLUSION: Clinical pharmacy can reduce adverse drug events in cancer patients. More robust and economic evaluations are still required to support its development in everyday practice.

Serious Adverse Drug Reactions to Antipsychotics in Minors with Multiple Disabilities: Preventability and Potential Cost Savings by Therapeutic Drug Monitoring.

INTRODUCTION: Children and adolescents with multiple disabilities and mental disorders (CAMD) are frequently treated with antipsychotic drugs. However, CAMD are particularly susceptible to serious adverse drug reactions (sADRs). This retrospective study examined the frequency of sADRs to antipsychotics in CAMD. Further, the potential preventability of these sADRs through therapeutic drug monitoring (TDM) and the potential socio-economic benefits of TDM were explored. METHODS: Routine clinical data of all patients treated at a specialized psychiatric clinic for CAMD between January 2017 and December 2018 were retrospectively examined. Data on the occurrence of sADRs (definition according to the European Medicines Agency), their causality with antipsychotics, as well as their preventability (Schumock criteria) were extracted from patient files. The prolongation of the hospital stay due to sADRs was calculated, and the cost savings were estimated if TDM had been applied. The data were based on a subsample of the KiDSafe project, supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. RESULTS: One hundred two CAMD who were administered at least one antipsychotic drug during inpatient treatment were identified. Of these patients, 22 (21.6%) sADRs with a possible causal relationship with the antipsychotic treatment were documented. Eleven sADRs (50%) could potentially have been prevented through TDM. Mitigating sADRs through TDM likely would have prevented prolonged hospital stays and thus conferred considerable savings for health insurance companies. DISCUSSION: The routine implementation of TDM is urgently recommended for antipsychotic treatment in CAMD to increase drug therapy safety.

Incidence and management of patients with methotrexate delayed elimination in the clinical practice: A Delphi study.

INTRODUCTION: High-dose methotrexate (HDMTX) is administered for the treatment of some cancers. HDMTX is usually safe but may crystallize in renal tubules causing acute kidney injury (AKI). Consequently, MTX elimination is delayed, resulting in a severe and life-threatening condition. No studies have been published about the impact of MTX toxicity in Spain. This study aims to estimate the incidence and management of MTX delayed elimination and toxicity. METHODS: A two-round Delphi study was performed to reach consensus between 10 medical experts on haemato-oncology and paediatric oncology with experience in the management of HDMTX treated patients from leading Spanish hospitals. An online questionnaire was developed based on national and international guidelines and previous evidence regarding HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile ranges were calculated, and incidence data were extrapolated to the Spanish general population. RESULTS: Out of 1.475 patients estimated to receive HDMTX treatment annually in Spain, 27.5% present MTX delayed elimination and 11.6% develop HDMTX-induced AKI (35.4% with severe systemic toxicities (>grade 3) and 18.8% develop chronic renal disease). Mortality is estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (90%) for MTX serum level monitoring. All experts use increased supportive care and high leucovorin as first-line treatment. Available treatments in experts' hospitals in case toxicity persists are haemodialysis (90% of hospitals), glucarpidase (60%) and hemofiltration (50%). Most prevalent non-renal systemic toxicities are haematologic and mucositis (21-40% of patients). Patients with HDMTX-induced AKI require from intensive care (5% of patients), more than 3 sessions and 4 days of dialysis, and about 8.5 days of hospitalization (non-ICU patients) and 12 days in case of patients requiring ICU. CONCLUSIONS: These results are the first evidence regarding HDMTX-induced AKI in Spain. Incidence and mortality results are in line with previous studies. Clinical management is based on preventive measures and the treatment depend on the availability in the hospital. The need for effective, safe and rapid treatment for the reduction of MTX toxic levels and the improvement of monitoring methods were noted by experts as urgent needs. Further observational studies to validate these results would be needed.

Assessment of chemotherapy-related educational needs of colorectal cancer patients.

AIM: Aim of our study was to evaluate cancer patients' knowledge about their chemotherapy regimens in order to assess educational needs of patients. METHODS: Study was conducted on 58 colorectal carcinoma patients who were treated in an outpatient chemotherapy unit. These patients had received a 2-page information pamphlet about their chemotherapy treatments before the commencement of treatment. During the first interview with patients, pharmacist collected demographic data and evaluated patients' knowledge about their medications using a standardized questionnaire. FINDINGS: Mean age of the patients was 59.6 ± 1.3 years; 65.5% were male. Majority (77.6%) of patients were graduates of primary school. Sixty-four percent of these had at least one comorbid disease. Median number of chemotherapy courses already received by patients was 4 (1-9). Fifty-nine percent reported that they did not receive any patient education and 43.1% reported that they did not receive any informative document. Twenty-nine percent of patients did not know what actions to take in case of nausea-vomiting; while 53.4% did not know how to react if their body temperature exceeded 38 °C and 25.9% had no idea about dietary necessities. About one-third of patients did not pay attention to oral care. CONCLUSION: Our study showed that patients did not understand (or remember) the basic points about their chemotherapy sufficiently, but remembered the adverse effects they experienced occasionally. Pharmacists will have the chance to increase the level of knowledge of the patients receiving chemotherapy by providing patient education and follow-up.

Introducing a simple and cost-effective RT-PCR protocol for detection of DPYD*2A polymorphism: the first study in Kurdish population.

PURPOSE: Fluoropyrimidines, the major chemotherapeutic agents in various malignancies treatment, are metabolized by dihydropyrimidine dehydrogenase (DPD). DPD deficiency can lead to severe and sometimes fatal toxicity. In the present study, we developed a simple protocol to detect the DPYD*2A variant. Common side effects in patients treated with these drugs were also evaluated in a Kurdish population. METHOD: We established a reverse-transcriptase polymerase chain reaction (RT-PCR) technique for detection of DPYD*2A. Sanger sequencing was used to confirm the results. 121 Kurdish patients receiving fluoropyrimidine derivatives were enrolled, and clinical information regarding the dosage and toxicity was analyzed. RESULTS: Our RT-PCR method was able to detect one patient with heterozygous state for DPYD*2A (0.8%). The most observed adverse drug reactions were tingling, nausea, and hair loss. The frequency of patients with the toxicity of grade 3 or worse was 6.6%. CONCLUSION: This was the first study that detect DPYD*2A polymorphism in the Kurdish population. Our method was successfully able to detect the DPYD*2A variant and, due to its simplicity and cost-effectiveness, it may be considered as an alternative to the current methods, especially in developing countries. Our detected polymorphism rate at 0.8% is comparable with other studies. Despite the low rate of DPYD*2A polymorphism, pharmacogenetics assessment before beginning the treatment process is highly recommended due to its association with a high risk of severe toxicity.

Assessment of cisplatin-induced nephrotoxicity and its associated factors among cervical cancer patients in the leading tertiary hospital in Kenya.

INTRODUCTION: Cisplatin is the widely used antineoplastic agent in managing cervical cancer despite nephrotoxicity being a major concern. In addition, there was a paucity of data about the degree of nephrotoxicity due to cisplatin in the study setting. Therefore, this study aimed to investigate the prevalence of cisplatin nephrotoxicity among cervical patients. METHODS: A retrospective cross-sectional study was conducted at the Cancer Treatment Centre of Kenyatta National Hospital among 100 cervical cancer patients treated with a cisplatin regimen. Simple random sampling was employed to the recruit medical record of patients. This study used a data abstraction tool to extract the patients' relevant socio-demographic and clinical characteristics. The data were analysed using Statistical Package for Social Sciences version 25.0 software. Frequency tables and figures were used to present the findings of the study. Binary logistic regression analysis was used to determine factors associated with cisplatin nephrotoxicity. RESULTS: The study showed a mean age of 52.09 ± 10.44 years. The prevalence rate of cisplatin-induced nephrotoxicity in cervical cancer patients was 45%. Of these patients, 36% and 9% patients had grade 1 and 2 nephrotoxicities, respectively. Comorbidities (crude odd's ratio (COR) = 3.05, 95% confidence interval [CI] = 1.3-7.02, p = 0.011), hypertension (COR = 3.0, 95% CI = 1.1-7.8, p = 0.03), and more than three cycles of cisplatin treatment (adjusted odd's ratio = 4.5, 95% CI = 1.19-17.0, p = 0.027) were significant factors of nephrotoxicity. CONCLUSION: The prevalence of cisplatin-induced nephrotoxicity among cervical cancer patients was high in the study setting. Comorbidities, number of cycles and types of comorbidities were significant factors associated with cisplatin nephrotoxicity.

An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.

Kappa opioid receptor (κOR) agonists lack the abuse liability and respiratory depression effects of clinically used mu opioid receptor (µOR) analgesics and are hypothesized to be safer alternatives. However, κOR agonists have limiting adverse effects of their own, including aversion, sedation, and mood effects, that have hampered their clinical translation. Studies performed over the last 15 years have suggested that these adverse effects could result from activation of distinct intracellular signaling pathways that are dependent on ß-arrestin, whereas signaling downstream of G protein activation produces antinociception. This led to the hypothesis that agonists biased away from ß-arrestin signaling would have improved therapeutic windows over traditional unbiased agonists and allow for clinical development of analgesic G-protein-biased κOR agonists. Given a recent controversy regarding the benefits of G-protein-biased µOR agonists, it is timely to reassess the therapeutic promise of G-protein-biased κOR agonists. Here we review recent discoveries from preclinical κOR studies and critically evaluate the therapeutic windows of G-protein-biased κOR agonists in each of the adverse effects above. Overall, we find that G-protein-biased κOR agonists generally have improved therapeutic window relative to unbiased agonists, although frequently study design limits strong conclusions in this regard. However, a steady flow of newly developed biased κOR agonists paired with recently engineered behavioral and molecular tools puts the κOR field in a prime position to make major advances in our understanding of κOR function and fulfill the promise of translating a new generation of biased κOR agonists to the clinic.

Assessment of Causality in Hospitalized Children With Aminoglycoside-Related Nephrotoxicity.

OBJECTIVE: To evaluate the incidence of aminoglycoside-related nephrotoxicity and ascertain drug causality and its risk factors. METHODS: This prospective study was conducted from January, 2019 to January, 2021, and recruited 110 consecutively admitted children aged 1 month to 12 years, receiving aminoglycosides for ≥4 days. Drug causality was assessed using Liverpool adverse drug reaction causality assessment tool. RESULTS: 42 (38.2%) children developed acute kidney injury (AKI), with 71 (64.5%) having composite nephrotoxicity (AKI and/or tubular-dysfunction). Only 17 (15.5%) had AKI definitively attributable to aminoglycosides. Hypotension [OR 0.016 (95% CI 0.01-0.71), P=0.03], PRISM-III score 20-29% [OR 55.48 (95% CI 3.66-840.53), P=0.004] and post-surgery patients [OR 3.2 (95% CI 1.01-10.1), P=0.047] were independent predictors of AKI. Conclusions: Only a small proportion of children receiving aminoglycosides had AKI definitively attributable to the drug.

Análise de intervenções farmacêuticas utilizando um instrumento de acompanhamento farmacêutico em uma Unidade de Terapia Intensiva Pediátrica / Analysis of pharmaceutical interventions using a pharmaceutical monitoring instrument in a Pediatric Intensive Care Unit

Introdução: A pediatria apresenta um cenário bastante específico devido ao uso de medicamentos off-label e carência de estudos científicos direcionados à utilização de medicamentos por essa população. Assim, o farmacêutico clínico pode contribuir na identificação e prevenção de problemas relacionados a medicamentos.Métodos: Estudo de coorte retrospectivo realizado em uma unidade de terapia intensiva pediátrica de um hospital universitário do Rio Grande do Sul. Foram analisadas as intervenções farmacêuticas realizadas entre março de 2016 a julho de 2018 por farmacêuticos clínicos. Tais intervenções foram reclassificadas conforme os critérios de um instrumento de acompanhamento farmacêutico (bundle) utilizado na rotina. Foi realizada análise estatística descritiva das variáveis estudadas.Resultados: Das 582 intervenções farmacêuticas analisadas, as categorias mais prevalentes foram dose (n = 97; 16,7%), necessidade (n = 92; 15,8%) e forma farmacêutica (n = 56; 9,6%). Após reclassificação das intervenções farmacêuticas utilizando o bundle, os critérios mais prevalentes foram: critério 1 (revisão da farmacoterapia; n = 285; 49%), critério 4 (analgesia; n = 78; 13,4%) e critério 10 (antimicrobianos; n = 65; 11,2%). As classes de medicamentos mais frequentes foram os do sistema nervoso (n = 213; 36,6%) e os anti-infecciosos gerais para uso sistêmico (n = 115; 19,8%). A taxa de adesão das intervenções farmacêuticas pela equipe médica foi de 85,1%.Conclusão: A classificação das intervenções farmacêuticas utilizando o bundle pode contribuir no aperfeiçoamento do instrumento tornando-o mais viável para uso na unidade de terapia intensiva pediátrica e direcionar o trabalho do farmacêutico clínico nas situações que geram mais problemas relacionados a medicamentos.

Introduction: Pharmaceutical interventions in the pediatric setting are highly peculiar due to the use of off-label drugs associated with the lack of scientific studies on the use of drug therapies in this population. Thus, clinical pharmacists may help identify and prevent drug-related problems.Methods: We conducted a retrospective cohort study in the pediatric intensive care unit of a teaching hospital in Rio Grande do Sul, Brazil. Pharmaceutical interventions conducted between March 2016 and July 2018 were analyzed by clinical pharmacists. These interventions were reclassified according to the criteria of a routine pharmaceutical monitoring instrument (care bundle). We conducted a descriptive statistical analysis of study variables.Results: Of 582 pharmaceutical interventions analyzed, the most prevalent categories were dose adjustment (n = 97; 16.7%), need for drug therapy (n = 92; 15.8%), and dosage forms (n = 56; 9.6%). After reclassification of pharmaceutical interventions, the most prevalent criteria were criterion 1 (review of drug therapy; n = 285; 49%), criterion 4 (analgesia; n = 78; 13.4%), and criterion 10 (antimicrobials; n = 65; 11.2%). The most common drug classes were nervous system agents (n = 213; 36.6%) and anti-infectives for systemic use (n = 115; 19.8%). The rate of adherence to pharmaceutical interventions by the medical team was 85.1%.Conclusions: The classification of pharmaceutical interventions according to the pharmaceutical care bundle may help improve the instrument, allowing its use in the pediatric intensive care unit and guiding clinical pharmacists in situations causing drug-related problems.

Initial assessment of an interprofessional team-delivered telehealth program for patients with epilepsy.

INTRODUCTION: Epilepsy affects 3.5 million people in the United States (US). Rural-dwelling individuals have less access to healthcare and consequently poorer health outcomes. This study describes the outcomes of an interprofessional telehealth program for rural-dwelling individuals with epilepsy in one US state. METHODS: An academic medication therapy management pharmacist provided clinical services to rural-dwelling individuals with epilepsy between November 2015 and June 2018, using video-conferencing technology and follow-up telephonic consultation. Data collected included: demographics, prescribed seizure medications, comorbidities, drug-drug and drug-disease interactions, adverse drug reactions, therapeutic duplications, dose-related safety concerns, adherence concerns, and recommendations to resolve identified issues. Data were summarized using appropriate descriptive statistics. RESULTS: A total of 168 patients (51% male, mean age 28 ± 15 years), participated in this pilot study. Most participants (94%) were prescribed at least one seizure medication including: benzodiazepines (n = 89), lamotrigine (n = 58), and levetiracetam (n = 56). The majority (55%) had at least one comorbidity including: mood disorders (n = 49) and psychiatric disorders (n = 26). Common medications with reported precautions for people with a seizure history were: selective serotonin reuptake inhibitors (n = 18), second-generation atypical antipsychotics (n = 17) and benzodiazepines (n = 16). Participants had at least one: drug-disease interaction (33%), drug-drug interaction (54%), adverse drug reaction (37%), therapeutic duplication (13%); dose-related safety concerns (35%); and medication utilization concerns (13%). DISCUSSION: This pharmacist-delivered pilot program was effective in: reaching underserved patients with epilepsy, identifying and recommending resolutions to medication-related problems, and demonstrating the value of pharmacists in an interprofessional team. Further work is warranted to identify telehealth strategies to reduce medication associated problems.

5-Fluorouracil and Capecitabine: Assessment and Treatment of Uncommon Early-Onset Severe Toxicities Associated With Administration.

BACKGROUND: Uncommon early-onset severe toxicities from 5-fluorouracil (5-FU) and capecitabine can be fatal if early warning signs are not recognized and treated promptly. OBJECTIVES: This article delineates the differences between expected side effects and uncommon early-onset severe toxicities from 5-FU and capecitabine. It also provides background for understanding the reasons patients may develop these toxicities and reviews the efficacy of standard supportive care against a novel therapy (uridine triacetate). METHODS: A panel of nurses convened to review the literature about toxicities associated with 5-FU and capecitabine administration and determined methods to educate nurses about toxicities and treatment. FINDINGS: Standard supportive care for 5-FU and capecitabine toxicities is associated with high fatality rates. Uridine triacetate treatment within 96 hours of administration is associated with survival.

Assessment Tools for Peripheral Neuropathy in Pediatric Oncology: A Systematic Review From the Children's Oncology Group.

Peripheral neuropathy is a known side effect of several chemotherapy agents, including vinca alkaloids and platinum-based chemotherapy. Early recognition and monitoring of this side effect is an important role of the pediatric oncology nurse. There are a variety of peripheral neuropathy assessment tools currently in use, but the usefulness of these tools in identifying and grading neuropathy in children varies, and there is currently no standardized tool in place to evaluate peripheral neuropathy in pediatric oncology. A systematic review was performed to identify the peripheral neuropathy assessment tools that best evaluate the early onset and progression of peripheral neuropathy in pediatric patients receiving vincristine. Because of the limited information available in pediatric oncology, this review was extended to any pediatric patient with neuropathy. A total of 8 studies were included in the evidence synthesis. Based on available evidence, the pediatric-modified Total Neuropathy Scale (ped-m TNS) and the Total Neuropathy Score-pediatric version (TNS-PV) are recommended for the assessment of vincristine-induced peripheral neuropathy in children 6 years of age and older. In addition, several studies demonstrated that subjective symptoms alone are not adequate to assess for vincristine-induced peripheral neuropathy. Nursing assessment of peripheral neuropathy should be an integral and regular part of patient care throughout the course of chemotherapy treatment.

Assessment of indomethacin oral spray for the treatment of oropharyngeal mucositis-induced pain during anticancer therapy.

PURPOSE: The efficacy and safety of indomethacin (IM) oral spray (OS) as a pain control therapy for oropharyngeal mucositis due to anticancer chemo- and radiotherapy were assessed in patients with head and neck carcinomas and haematological tumours. METHOD: We observed 35 patients (male/female, 20/15; 53 ± 17 years) with oropharyngeal mucositis who were treated with IM-OS preparation for pain relief at University of Tsukuba Hospital, Japan. Analgesic effects were assessed using the six-grade face scale for pain in 28 patients at the start of IM oral spray treatment. Systemic exposure was assessed by determining urinary excretions of IM in seven patients. RESULTS: Pain relief was achieved in 26 (93%) patients at 25 (5-60) min after applying the IM-OS preparation (15.6 ± 3.4 µg/kg) and analgesic effects were maintained for 120 (10-360) min. The pain was significantly decreased after using the spray (3.6 ± 0.7 vs. 2.4 ± 0.9, p < 0.01). Moreover, urinary IM excretion rates after applying the IM spray preparation were 1.8 ± 0.8% of the IM oral spray dose (130.5 ± 77.7 µg/kg/day), which was markedly lower than that following oral administration of IM (60%). No adverse events were observed following application of the spray. CONCLUSIONS: The present IM spray is an effective and safe preparation for pain relief and can be used as an alternative therapeutic option for oropharyngeal mucositis in cancer patients.

Contribution of Pharmacogenetic Testing to Modeled Medication Change Recommendations in a Long-Term Care Population with Polypharmacy.

BACKGROUND: Among long-term care facility residents, polypharmacy is common, and often appropriate, given the need to treat multiple, complex, chronic conditions. Polypharmacy has, however, been associated with increased healthcare costs, adverse drug events, and drug interactions. The current study evaluates the potential medication cost savings of adding personalized pharmacogenetic information to traditional medication management strategies. METHODS: One hundred and twelve long-term care residents completed pharmacogenetic testing for targeted variants in the following genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/CYP3A5, HTR2A, HTR2C, SLC6A4, SLC6A2 COMT, OPRM1, SLCO1B1, VKORC1 and MTHFR. Following reporting of the IDgenetix Polypharmacy® test results, an internal medication management assessment was performed by a licensed clinical pharmacist to identify potential opportunities for regimen optimization through medication changes or discontinuations. The medication cost differences before and after the pharmacogenetic-guided review were assessed. RESULTS: Medication review following pharmacogenetic result reporting identified 54 patients (48.2%) with a total of 132 drug change recommendations (45 reductions; 87 replacements) and an average of 2.4 proposed medication changes (range 1-6) per patient. Medication cost savings related to the identified reduction and replacement opportunities exceeded the cost of testing and are estimated to be US$ 1300 (year 2016 cost) per patient annually assuming full implementation. CONCLUSION: Compared with traditional medication review, pharmacogenetic testing resulted in a 38% increase in the number of patients with current medication change opportunities and also offered valuable genetic information that could be referenced to personalize future prescribing decisions for all patients.

Adverse effects of clozapine in older patients: epidemiology, prevention and management.

Research into the use of clozapine in older people is somewhat scarce. Clozapine is associated with serious adverse effects such as agranulocytosis, seizures, myocarditis and metabolic syndrome. Other common undesirable effects such as sedation, constipation (which can be fatal), urinary incontinence and hypersalivation further limit its use. These adverse effects are particularly important for the use of clozapine in older people, who are generally more susceptible to medication-related adverse effects. Whilst clozapine should be used with caution in elderly people, strict monitoring procedures can help to prevent harmful effects through early detection, and certain management techniques exist to minimise them. This review outlines the epidemiology of clozapine-related adverse effects in older people and discusses potential prevention and management strategies.