RESUMEN
AIMS: Prescribing information should follow a defined structure to help prescribers easily find required information. Often information appears in different sections of Summaries of Product Characteristics (SmPCs) in an inconsistent way. Still unknown is how this inconsistency affects absolute contraindications and how it can be improved. Thisstudy aimed to evaluate the structure of absolute contraindications in SmPCs based on absolute drug-drug contraindications (DDCI) in the section 'contraindications' and references to sections 'special warnings and precautions for use' (here as 'warnings') and 'interaction with other medicinal products and other forms of interaction' (here as 'interactions'). METHODS: SmPCs of 693 commonly prescribed drugs were analysed regarding absolute DDCI in 'contraindications' sections. References to sections on 'warnings' and 'interactions' were evaluated to characterize information provided about DDCI. RESULTS: Of 693 analysed SmPCs, 138 (19.9%) contained ≥1 absolute DDCI. Of 178 SmPCs that referred to sections on 'warnings' or 'interactions', 131 (73.6%) did not contain further information on absolute DDCI, whereas 47 (26.4%) did. Such additional information was found in sections on 'interactions' and 'warnings' in 41 (87.2%) and 9 (19.1%) SmPCs, respectively. CONCLUSIONS: Information regarding absolute DDCI was found not only in sections on 'contraindications' but also in sections on 'warnings' and 'interactions'. Information was not given with consistently straightforward phrasing and structure and so can leave uncertainty for prescribers. To improve drug safety, clear definitions and wording for absolute and relative contraindications should be provided, ideally in tables.
Asunto(s)
Contraindicaciones de los Medicamentos , Etiquetado de Medicamentos , Humanos , Etiquetado de Medicamentos/normasRESUMEN
AIMS: Automated checks for medication-related problems have become a cornerstone of medication safety. In many clinical settings medication checks remain confined to drug-drug interactions because only medication data are available in an adequately coded form, leaving possible contraindicated drug-disease combinations unaccounted for. Therefore, we devised algorithms that identify frequently contraindicated diagnoses based on medication patterns related to these diagnoses. METHODS: We identified drugs that are associated with diseases constituting common contraindications based on their exclusive use for these conditions (such as allopurinol for gout or salbutamol for bronchial obstruction). Expert-based and machine learning algorithms were developed to identify diagnoses based on highly specific medication patterns. The applicability, sensitivity and specificity of the approach were assessed by using an anonymized real-life sample of medication and diagnosis data excerpts from 3506 discharge records of geriatric patients. RESULTS: Depending on the algorithm, the desired focus (i.e., sensitivity vs. specificity) and the disease, we were able to identify the diagnoses gout, epilepsy, coronary artery disease, congestive heart failure and bronchial obstruction with a specificity of 44.0-99.8% (95% CI 41.7-100.0%) and a sensitivity of 3.8-83.1% (95% CI 1.0-86.1%). Using only medication data, we were able to identify 123 (51.3%) of 240 contraindications identified by experts with access to medication data and diagnoses. CONCLUSION: This study provides a proof of principle that some key diagnosis-related contraindications can be identified based on a patient's medication data alone, while others cannot be identified. This approach offers new opportunities to analyse drug-disease contraindications in community pharmacy or clinical routine data.
Asunto(s)
Algoritmos , Gota , Humanos , Anciano , Interacciones Farmacológicas , Documentación , AlopurinolRESUMEN
The randomized AMBORA trial showed that medication errors are frequent in patients treated with oral antitumor therapeutics and that they can be substantially reduced by an intensified clinical pharmacological/pharmaceutical care program. While randomized controlled trials are essential to generate clinical evidence, their generalizability in real-world is not always given. The AMBORA care program was implemented in clinical routine within the AMBORA Competence and Consultation Center (AMBORA Center) at the Comprehensive Cancer Center Erlangen-EMN, allowing a thorough comparison of medication error frequencies and characteristics. Our primary analysis compared data at therapy initiation of new oral antitumor therapeutics from the AMBORA trial intervention group (n = 98) and the AMBORA Center (n = 142). Medication errors involving the oral antitumor therapeutics were twofold higher in real-world compared to the randomized controlled trial (mean 0.83 ± 0.80 per patient vs. 0.41 ± 0.53, P < 0.001). We observed more complex oral antitumor therapeutic regimens, a higher median number of medications, and a higher ECOG status in clinical routine vs. the randomized trial. A high percentage of medication errors was completely solved in both groups (85.7% vs. 88.3%, ns). Medication error characteristics within the complete medication (oral antitumor therapeutics and concomitant medication) were similar in both groups (e.g., patient-related causes, drug-drug/drug-food interactions). Taken together, medication errors were even more frequent in clinical routine than in the randomized controlled trial and a high rate was solved in clinical routine by a clinical pharmacological/pharmaceutical care program.
Asunto(s)
Antineoplásicos , Errores de Medicación , Humanos , Errores de Medicación/prevención & control , Errores de Medicación/estadística & datos numéricos , Administración Oral , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias/tratamiento farmacológico , AdultoRESUMEN
PURPOSE: Implementation science endeavors to facilitate the translation of evidence-based research into clinical routine. The clinical pharmacological/pharmaceutical care program evaluated in the randomized AMBORA trial on medication safety with oral antitumor therapeutics (OAT) optimizes care delivery and provides significant benefits for patients, treatment teams, and health care systems. Thus, we aimed to investigate the implementation of this care program within the AMBORA Competence and Consultation Center (AMBORA Center). METHODS: The AMBORA Center within a University Comprehensive Cancer Center offered several services (eg, patient consultations) and was evaluated according to the RE-AIM framework. This multicenter hybrid type III trial focused on implementation outcomes (eg, patient recruitment, referring units, evaluation of services) while concurrently investigating effectiveness (eg, side effects, medication errors). Quantitative and qualitative assessments were combined. RESULTS: The AMBORA Center conducted over 800 consultations with 420 patients in seven institutions. The primary end point of counseling 70% of patients treated with OAT was not reached. Patients were referred by 15 treatment units compared with 11 units in the AMBORA trial. On the basis of heterogeneous referral rates and characteristics across the institutions, barriers and facilitators of the implementation process were derived. Several survey results (eg, stakeholder interviews, online/paper-based questionnaires) reflected a high appreciation of services by patients and health care professionals. The severity of 60.1% (178 of 296) of detected side effects improved, and 86.3% (297 of 344) of medication errors were resolved. CONCLUSION: Despite not reaching the primary implementation outcome, the AMBORA Center included more treatment units and demonstrated patient benefit of the AMBORA care program by meeting all effectiveness outcomes. We outlined quantitative and qualitative implementation characteristics to enhance outreach and foster further dissemination of centers to optimize medication safety with OAT.
RESUMEN
Generating evidence for the efficacy of an intervention is not sufficient to guarantee its implementation in real-world settings. The randomized AMBORA trial (Medication Safety with Oral Antitumor Therapy) demonstrated that an intensified clinical pharmacological/pharmaceutical care program has substantial benefits for patients, treatment teams, and the healthcare system. Thus, we are now investigating its implementation into routine care within the AMBORA Competence and Consultation Center (AMBORA Center). We perform a multicenter type III hybrid trial following the RE-AIM framework to assess the clinical effectiveness of this care program under real-world conditions, while evaluating the implementation outcomes. Semi-structured stakeholder interviews based on the Consolidated Framework for Implementation Research (CFIR) have been conducted to identify barriers and facilitators. So far, 332 patients treated with oral antitumor drugs have been referred to the AMBORA Center by 66 physicians from 13 independent clinical units. In 20 stakeholder interviews (e.g., with clinic directors), 30% (6/20) of the interviewees anticipated possible barriers which may partly hinder sustainable implementation (e.g., unavailable consultation rooms). Furthermore, important facilitators (e.g., operational processes) were identified. This methodological description adds knowledge on how to structure a hybrid effectiveness-implementation trial and proposes multilevel implementation strategies to improve the medication safety of oral antitumor therapy.
RESUMEN
Drug-related problems (e.g., adverse drug reactions, ADR) are serious safety issues in patients treated with oral anticancer therapeutics (OAT). The previously published randomized AMBORA trial showed that an intensified clinical pharmacological/pharmaceutical care program within the first 12 weeks of treatment reduces the number and severity of ADR as well as hospitalization rates in 202 patients. The present investigation focused on unscheduled hospitalizations detected within AMBORA and analyzed the characteristics (e.g., frequency, involved OAT) and cost of each hospital stay. To estimate the potential savings of an intensified care program in a larger group, the absolute risk for OAT-related hospitalizations was extrapolated to all insureds of a leading German statutory health insurance company (AOK Bayern). Within 12 weeks, 45 of 202 patients were hospitalized. 50% of all unscheduled hospital admissions were OAT-related (20 of 40) and occurred in 18 patients. The mean cost per inpatient stay was EUR 5873. The intensified AMBORA care program reduced the patients' absolute risk for OAT-related hospitalization by 11.36%. If this care program would have been implemented in the AOK Bayern collective (3,862,017 insureds) it has the potential to reduce hospitalization rates and thereby cost by a maximum of EUR 4.745 million within 12 weeks after therapy initiation.
RESUMEN
INTRODUCTION: The number of prescriptions and costs of oral anticancer drugs are increasing. Therapy discontinuation due to, for example, side effects, progression, or death, often lead to medication wastage. While evidence exists for the economic value of wasted injectable chemotherapeutics, there is a lack of data for oral anticancer drugs in Germany. METHODS: The multicenter AMBORA trial investigated 202 patients, who had been newly started on new oral anticancer drugs, over 12 weeks and analyzed the outpatient prescription data of patients who discontinued treatment. The amount of medicines wasted and their costs were determined using the pharmacy retail price. Defined daily doses and prescription data from the AOK Bayern, a German statutory health care insurance company, were used to extrapolate these costs. RESULTS: Within 12 weeks, 24.8 % of the AMBORA patients discontinued oral anticancer treatment (50 of 202). Prescription data of 34 patients were evaluable. In total, 1,693 tablets/capsules with a value of 112,212 euros were wasted. The approximate extrapolation to the prescription volume of the AOK Bayern resulted in an estimated wastage of 3.49 million euros in 12 weeks. DISCUSSION: Medication wastage due to discontinuation of new oral anticancer drug therapy leads to a considerable financial burden. Regarding rising prescription numbers and therapy costs in oncology, measures to reduce wastage of oral anticancer drugs should be initiated. CONCLUSION: Clinical pharmacological / pharmaceutical care including medication reconciliation and review, side effect management and patient counseling to optimize adherence and medication intake behavior, contributes to a reduction of therapy discontinuations, thereby reducing drug wastage. To further reduce drug wastage small (initiation) packages, which are currently not always available for an economic prescription, play an important role. The practice of partial prescription fills, which is already practiced internationally, should also be further discussed in Germany.
Asunto(s)
Antineoplásicos , Farmacias , Antineoplásicos/efectos adversos , Costos y Análisis de Costo , Costos de los Medicamentos , Alemania , Humanos , Oncología MédicaRESUMEN
Oral antitumor therapeutics (OAT) bear a high risk for medication errors, e.g., due to drug-drug or drug-food interactions or incorrect drug intake. Advanced age, organ insufficiencies, and polymedication are putting uro-oncological patients at an even larger risk. This analysis sets out to (1) investigate the frequency and relevance of medication errors in patients with prostate cancer or renal cell carcinoma treated with OAT and (2) compile recommendations for clinical practice. This post-hoc subgroup analysis used data collected in the randomized AMBORA trial (2017-2020; DRKS00013271). Clinical pharmacologists/pharmacists conducted advanced medication reviews over 12 weeks after initiation of a new oral regimen and assessed the complete medication process for drug-related problems. Medication errors related to either the OAT, prescribed or prescription-free concomitant medication, or food were classified regarding cause and severity. We identified 67 medication errors in 38 patients within the complete medication within 12 weeks. Thereof, 55% were detected at therapy initiation, 27% were caused by the patients, and 25% were drug-drug or drug-food interactions. Problem-prone issues are summarized in a 'medication safety table' to provide recommendations for clinical practice in uro-oncology. Tailored strategies including intensified care by clinical pharmacologists/pharmacists should be implemented in clinical practice to improve medication safety.
RESUMEN
Patients treated with oral anticancer agents (e.g., kinase inhibitors) are a high-risk population for medication errors due to, for example, polymedication, age, and limited adherence. Systematic evaluations regarding frequencies and causes of medication errors and resulting harm are lacking. Our previously published multicenter randomized AMBORA trial revealed that an intensified support by clinical pharmacologists/pharmacists for patients and the treatment team considerably reduced drug-related problems and improved patient-reported outcomes. Using this database, we performed a comprehensive, additional analysis focusing on medication errors related to the patients' complete medication with consideration of the antitumor agents, concomitantly administered drugs, and herb/food intake. Two hundred two patients starting a new oral anticancer drug regardless of the tumor entity were included. Clinical pharmacologists/pharmacists performed advanced medication reviews for 12 weeks. Medication errors were characterized regarding type, cause, patient harm, and the involved medicines. We detected 1.7 medication errors per patient (335/202). Of the medication errors (216/335), 64.5% occurred within the concomitant medication. Patients caused 28.4% of the medication errors. There were 67.8% detected immediately after the start of the new oral regimen, and 14.9% resulted in temporary harm. Drug-drug or drug-food interactions accounted for 24.8% of the medication errors. Patients and physicians need to be addressed in strategies for systematic reduction of medication errors during treatment with new oral antitumor drugs. Clinical decision support systems focusing on drug-drug interactions capture only a minority of the medication errors. Specialists with expertise in clinical pharmacology/pharmacy should support both the treating physicians as well as the patients for improved patient safety.
Asunto(s)
Antineoplásicos/uso terapéutico , Interacciones Farmacológicas , Interacciones Alimento-Droga , Errores de Medicación/estadística & datos numéricos , Neoplasias/tratamiento farmacológico , Polifarmacia , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos/uso terapéutico , Antiulcerosos/uso terapéutico , Antihipertensivos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Comorbilidad , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/epidemiología , Sistemas de Apoyo a Decisiones Clínicas , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipolipemiantes/uso terapéutico , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Hormonas Tiroideas/uso terapéutico , Vitaminas/uso terapéuticoRESUMEN
Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.
RESUMEN
PURPOSE: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS: Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS: Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION: Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.
Asunto(s)
Antineoplásicos/administración & dosificación , Drogas en Investigación/administración & dosificación , Neoplasias/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Drogas en Investigación/efectos adversos , Determinación de Punto Final , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Estudios ProspectivosRESUMEN
BACKGROUND: Many oral anti-cancer drugs have come onto the market in the past 20 years. For example, kinase inhibitors, such as the BCR-ABL and BRAF inhibitors, have markedly improved the treatment of chronic myeloid leukemia and melanoma. In this review, we discuss the special challenges posed by poor adherence, drug-drug interactions with other substances, and side effects, among other problems, and the ways in which these challenges can be met. METHODS: A selective search was carried out in PubMed for original and review articles on the safety of new oral anti-cancer drugs. Guidelines and current Summaries of Product Characteristics (SmPC) were also considered in the analysis. RESULTS: Review articles have pointed out numerous safety concerns with oral anti-cancer drugs. One of these is adherence, on which highly variable figures are available (with mean non-adherence rates ranging from 0 to 54%). The absorption of approximately half of these drugs is influenced by the patient's diet, and that of approximately 20% by gastric pH (Caution: proton-pump inhibitors may influence bioavailability). 70% of the active substances are metabolized primarily by CYP3A4, which means that their pharmacokinetics can be altered by grapefruit juice and CYP3A4 modulators. The prevention, detection, and treatment of side effects (which can be gastrointestinal, cutaneous, cardiovascular, or other) is a highly important matter. CONCLUSION: The increasing use of oral anti-cancer drugs confronts patients and treatment teams with special challenges. To optimize treatment outcomes, a multidisciplinary approach should be taken, involving physicians, pharmacists, and nurses. To improve medication safety, medication and side-effect management should be performed, and adherence should be regularly checked and systematically encouraged.