Irene Aquerreta

Potential Interaction between Methotrexate and Omeprazole

OBJECTIVE: To report a case of delayed elimination of high-dose methotrexate (MTX) associated with concomitant omeprazole administration. CASE SUMMARY: Delayed MTX elimination was observed in an 11-year-old white boy who concomitantly received high-dose MTX and omeprazole. The patients serum creatinine and liver function tests were normal during treatment and follow-up. The only medication we suspected of inhibiting MTX elimination was omeprazole 20 mg every 12 hours. Twenty-four hours after the first high-dose MTX cycle (15 g), omeprazole was discontinued. Thereafter, the patient received one high-dose MTX cycle without omeprazole every month for five months; MTX elimination was normal throughout MTX cycles 2 to 5. DISCUSSION: MTX is actively secreted in the distal tubules. The renal hydrogen/potassium adenosine triphosphatase (H+/K+-ATPase) pump makes the urine more acidic, by secreting hydrogen ions into the renal tubule and reabsorbing potassium ions. Active tubular secretion of MTX requires the activity of this pump because MTX is excreted with hydrogen ions. Omeprazole can inhibit renal elimination of the hydrogen ion and block the active tubular secretion of MTX. Therefore, the elimination half-life of MTX increases, which may result in potentially toxic concentrations of MTX. At a pH of approximately 5, as found in the renal tubules, pantoprazole is more slowly activated than omeprazole, reducing the incidence of unwanted reactions with sulfhydryl groups and adverse effects occurring outside of the gastric hydrogen pump. CONCLUSIONS: Based on the Naranjo probability scale, a probable drug interaction was observed. Omeprazole may delay MTX elimination; therefore, when prescribing MTX, an alternative to omeprazole should be considered.

Efficacy of an Adverse Drug Reaction Electronic Reporting System Integrated into a Hospital Information System

Background: Adverse drug reaction (ADR) spontaneous reporting is the primary method of postmarketing drug surveillance: although it is an important part of postmarketing drug surveillance, it is underused. Before 2004, almost no ADRs were reported in our 400-bed hospital. As an electronic hospital information system was available in our hospital, we developed a tool (ADR-RS-IHIS) for ADR reporting integrated into the hospital information system to facilitate reporting through easy use, automatic input of certain information, increased accessibility, real-time review, and intervention. Objective: To analyze the efficacy of the ADR-RS-IHIS in increasing ADR reporting to the national drug surveillance system, propose and implement improvements to increase ADR reporting, and evaluate the impact of these improvements, Methods: Every ADR reported through the ADR-RS-IHIS was evaluated retrospectively. Two study phases for evaluating ADR-RS-IHIS efficacy were identified. Phase I took place April 2004-August 2006; in April 2006, an interim analysis was performed to propose improvements. Phase II took place September 2006-April 2007 for evaluation of the impact made by the proposed improvements. Efficacy in the phase I and improvement impact on phase II were measured as the number of ADRs reported to the national drug surveillance system Results: The rate of ADRs reported per month to the national system increased from 0 before 2004 to 0.91 in phase I and 1.62 in phase II (2.25 if delayed reporting was considered). Improvement measures included: allowing nurses to report ADRs in the same way as physicians and pharmacists, automatic form filling of certain information from the electronic hospital information system, easier ADR report analysis, and automatic notification to the allergy department regarding suspected allergies. Conclusions: An ADR reporting system integrated into the electronic hospital information system is effective for increasing the number of ADRs reported to the national drug surveillance system. Allowing nurses to report ADRs in a manner similar to that of physicians and pharmacists, as well as automatic entry of certain data into the form, contributes to the improvement of the system.

Impacto clínico y económico de la incorporación del farmacéutico residente en el equipo asistencial

Resumen Objetivo Cuantificar el impacto de la integracion de un residente de Farmacia Hospitalaria en el equipo asistencial. Describir la sistematica de trabajo seguida. Metodo El residente se integro durante 8 meses en oncologia medica, unidad de cuidados intensivos y hospital de dia de oncologia. Las intervenciones se registraron y evaluaron mediante el programa informatico Atefarm®. Se registraron las caracteristicas, tipo y gravedad de los problemas y la aceptacion y coste evitado de las intervenciones. Resultados Se detectaron 2.415 problemas relacionados con los medicamentos (10 por dia y 3,6 por paciente) y se realizaron 2.545 intervenciones sobre 672 pacientes. Los mas frecuentes fueron la inadecuada duracion de los tratamientos y la conversion a via oral. El 61% de los errores fueron prevenidos. Un 65% de las intervenciones tuvo impacto sobre seguridad, 35% sobre eficiencia y 25% sobre efectividad. El 94% de las intervenciones fueron aceptadas. El coste evitado por farmaceutico/mes ascendio a 3.133 €. Conclusiones El farmaceutico integrado en los equipos asistenciales optimiza la terapia, reduce costes, previene efectos adversos y ofrece educacion sanitaria.

Results of a retrospective observational study of intermediate care staffed by hospitalists: Impact on mortality, co‐management, and teaching

BACKGROUND Hospitalized patients are complex and institutions have to face the high cost of critical care and the limited resources of the ward. Intermediate care appears as an attractive strategy to provide rational care according to patient needs. It is an interesting scenario to expand co-management and teaching. STUDY DESIGN Retrospective observational study. SETTING Intermediate care unit (ImCU) of a single academic hospital. PATIENTS AND METHODS 456 patients admitted from April 2006 to April 2010 were included in the study. Demographics, admission physiologic parameters and in-hospital mortality were recorded. We used the Simplified Acute Physiology Score II (SAPS II) as prognostic score system. Co-management with medical and surgical teams, and the number of training residents were evaluated. RESULTS In-hospital mortality was 20.6%, whereas the expected mortality was 23.2% based on SAPS II score. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (Rho = 1.0, p < 0.001). Co-management was performed with several medical and surgical teams, with an increase in perioperative comanagement of 22.7% (p = 0.014). The number of training residents in ImCU increased from 4.3% to 30.4% (p = 0.002) CONCLUSIONS An ImCU led by hospitalists showed encouraging results regarding patient survival and SAPS II is an useful tool for prognostic evaluation in this population. Intermediate care serves as an expansion of role for hospitalists; and clinicians, trainees and patients may benefit from co-management and teaching opportunities at this unique level of care.

Linezolid-induced haematological toxicity.

OBJECTIVE to determine the incidence of linezolid-induced haematological toxicity and study the influence of renal clearance on its appearance and the preventive effect of pyridoxine. METHODS a retrospective observational study was conducted. Every patient treated with linezolid in a university hospital during 6 months was included. Haematological toxicity was defined as a decrease of 25% in hemoglobin, of 25% in platelets and/or 50% in neutrophils from baseline. The incidence of haematological toxicity and the percentage decrease in analytical variables were compared in patients with and without renal failure (creatinine clearance lower than 50 mL/min), using the 30 mL/min threshold, and with or without pyridoxine; using Chi -Square and U Mann-Whitney tests, respectively. RESULTS thirty-eight patients were evaluated. Sixteen (42%) presented haematological toxicity (2 due to a decrease in haemoglobin, 9 in platelets and 8 in neutrophils). Two patients (5%) discontinued treatment due to thrombocytopenia. Toxicity incidence was similar in patients with and without renal failure, 42% vs 42%, p = 0.970, with more or less than 30 ml/min, 67% vs 40%, p = 0.369, or with or without pyridoxine, 47.8% vs 33%, p = 0.376. Patients with renal failure had a significantly greater reduction in platelet count, p = 0.0185. CONCLUSION forty-two percent of patients had haematological toxicity, being more frequent platelets and neutrophils reduction. This was not significantly higher in patients with renal failure or in those without pyridoxine. Greater reduction in platelet count was observed in patients with renal failure.

Evidence of clinical and economic impact of pharmacist interventions related to antimicrobials in the hospital setting

The purpose of this paper was to review the literature regarding the clinical and economic impact of pharmacist interventions (PIs) related to antimicrobials in the hospital setting. A PubMed literature search from January 2003 to March 2016 was conducted using the terms pharmacist* or clinical pharmacist* combined with antimicrobial* or antibiotic* or anti-infective*. Comparative studies that assessed the clinical and/or economic impact of PIs on antimicrobials in the hospital setting were reviewed. Outcomes were classified as: treatment-related outcomes (TROs), clinical outcomes (COs), cost and microbiological outcomes (MOs). Acceptance of pharmacist recommendations by physicians was collected. PIs were grouped into patient-specific recommendations (PSRs), policy, and education. Studies’ risk of bias was analyzed using Cochrane’s tool. Twenty-three studies were evaluated. All of them had high risk of bias. The design in most cases was uncontrolled before and after. PSRs were included in every study; five also included policy and four education. Significant impact of PI was found in 14 of the 18 studies (77.8%) that evaluated costs, 15 of the 20 studies (75.0%) that assessed TROs, 12 of the 22 studies (54.5%) that analyzed COs, and one of the two studies (50.0%) that evaluated MOs. None of the studies found significant negative impact of PIs. It could not be concluded that adding other strategies to PSRs would improve results. Acceptance of recommendations varied from 70 to 97.5%. Pharmacists improve TROs and COs, and decrease costs. Additional research with a lower risk of bias is unlikely to change this conclusion. Future research should focus on identifying the most efficient interventions.

CP-193 Clinical and economic impact of pharmacists´ interventions related to antimicrobials in the hospital setting: a systematic review

Background In hospital settings (HS), pharmacists´ interventions (PI) can contribute to rational use of antimicrobials. Due to scarce resources, the pharmacist’s time has to be dedicated to interventions with impact on patient outcomes and costs. Purpose A systematic review was conducted to summarise published evidence regarding clinical and/or economic outcomes of PI related to antimicrobials in HS to estimate the impact of PI and to identify strategies with higher impact. Material and methods A PubMed search of papers published from 2003 to March 2016 was conducted using the terms (’pharmacist*’ OR ‘clinical pharmacist*’) AND (’antimicrobial*’ OR ‘antibiotic*’ OR ‘anti infective*’). Additional references were identified from citations. Inclusion criteria were: comparative studies that assessed clinical or economic impact of PI regarding antimicrobials in HS or those that evaluated intermediate outcomes, microbiological impact or appropriate antimicrobial prescription (AAP). Exclusion criteria were: studies in paediatric, primary care or community settings, and evaluations of multidisciplinary teams. We collected: study design, type of PI, impact of PI and acceptance by physicians. Risk of bias of studies was analysed using Cochrane´s tool.1 Results 23 studies were included; all had a high risk of bias. Most frequent design was before and after without a control group (57%) and 83% were single centre studies. Identified PI were grouped into three types: specific recommendations (SR) (in 22 studies), policy (in 4) and education (in 3). Six studies combined various strategies. A significant positive impact of PI was found in 14 of 17 (82%) studies that evaluated costs, in 11 of 15 (73%) that studied AAP, in 9 of 18 (50%) that analysed clinical outcomes (CO), in 1 of 2 (50%) that assessed microbiological outcomes (MO) and in 3 of 7 (43%) that evaluated adverse drug events (ADE). A combination of SR, education and policy had the highest impact on AAP, CO and costs; SR and education on MO; and dose adjustment on ADE. 70–92% of recommendations were accepted. Conclusion Pharmacists´ interventions regarding antimicrobials had a positive impact on appropriate prescribing and patient outcomes, and decreased costs. Combinations of strategies seems to be superior to single strategies. Quality of published studies is poor and better studies are necessary to confirm these results. References and/or acknowledgements 1. Available at http://handbook.cochrane.org/chapter_8/8_5_the_cochrane_collaborations_tool_for_assessing_risk_of_bias.htm No conflict of interest

CP-168 Economic impact of clinical pharmacist´s interventions on antimicrobial therapy in critically ill patients

Background A clinical pharmacist (CP), as part of the healthcare team (HT), can contribute to adequate anti-infective use. Few studies have evaluated the economic impact of CP´s interventions (CPI) in the intensive care unit (ICU), and most consider only drug costs. Purpose To analyse the economic impact of CPI regarding antimicrobial therapy (AT) in the ICU. Material and methods We conducted a retrospective analysis of CPI regarding AT in the ICU over a 5 month period. The CP spends 5 hours/day, 5 days/week in the ICU. 33% of CPI are anti-infective related. Information regarding CPI is recorded daily in the hospital´s information system and includes the drug involved, type of intervention, acceptance by physicians and estimated costs (incremental and avoided) as a consequence of the CPI. These costs include changes in drugs, time and products for drug preparations and administration, and the pharmacist’s time. To estimate costs (incremental or avoided) we assumed that the change to the recommended and accepted therapy would have happened 2 days later the without CPI (CPI contribute to earlier changes). For sensitivity analysis, we considered that the change would have happened in 1–4 days. The ratio ‘avoided cost to invested money’ was calculated. Results 212 interventions were recorded, corresponding to 114 patients. Most frequent types of CPI were: modification of drug dose and/or interval (MD) (50.9%), drug discontinuation (DD) (22.6%), change to a more cost effective administration route (CR) (14.6%), initiate a drug (7.5%) and change to a more cost effective drug (CD) (2.4%). Physicians´ acceptance rate was 97.6%. Over the 5-month period, we estimated a total decrease in costs as a consequence of CPI of €7013 (34.8% decrease), corresponding to €33.1/intervention and €61.5/patient. According to sensitivity analysis, total savings varied from €2779 to €19 011. This estimation included the cost of the CP’s time during the studied period (€2859). Therefore, €3.5 were avoided per €1 invested in the CP. Types of CPI associated with greater total savings were (in decreasing order): DD, MD and CR(and per intervention: CD, CR and DD). Conclusion Having a CP as a member of the HT in the ICU performing interventions related to antimicrobials is economically beneficial. References and/or acknowledgements Thanks to the pharmacy service. No conflict of interest