Background: Drug-drug interactions (DDIs) are an important cause of adverse drug reactions (ADRs). Many studies have recently considered this issue, but most of them focus only on potential interactions and are often related to the hospital setting. A spontaneous reporting database could be a valuable resource for detection of ADRs associated with DDIs; however, data in the literature are limited. Objective: To detect those patients treated with potentially interacting drugs and the cases where reported adverse reactions are a possible consequence of DDIs, using an Italian spontaneous reporting database. Methods: The data were obtained from a database containing all reports of suspected ADRs from five Italian regions (January 1990 to December 2007) that are the main contributors to the Italian spontaneous reporting system. All reports containing at least two drugs, reported as being suspected of causing the ADR or as concomitant medication, were selected and a list of drug pairs was drawn up. We performed a search to verify which drug pairs are considered a potential DDI, using the Internet version of the DRUGDEX® system. For each report containing a potential DDI, we verified whether the description of the adverse reaction corresponded to the interaction effect. Results: The database contained 45 315 reports, of which 17 700 (39.1%) had at least two reported drugs. We identified 5345 (30.2%) reports with potential DDIs, and in 1159 (21.7%) of these reports a related ADR was reported. The percentage of reports with potential DDIs increased in relation to the number of concomitantly administered drugs, ranging from 9.8% for two drugs to 88.3% for eight or more drugs. The percentages of serious or fatal reports of ADRs associated with a DDI were significantly higher than other reports analysed. The mean age, percentage of male patients and the mean number of drugs were also significantly higher in reports with DDIs than in other reports. In 235 of 1159 reports (20.3%), both interacting drugs were recognized as suspect by the reporter. This percentage varies in relation to the drugs involved, ranging from 2% to about 65%. The most frequently reported interaction was digoxin and diuretics, but no fatal ADRs were reported with this combination. The combination of anticoagulant and antiplatelet agents was responsible for the greatest number of serious reactions and deaths. Conclusions: This study validates that spontaneous reporting, despite its limitations, can be an important resource for detecting ADRs associated with the concomitant use of interacting drugs. Moreover, our data confirm that DDIs could be a real problem in clinical practice, showing that more than one in five patients exposed to a potential DDI experienced a related ADR.

Identifying adverse drug reactions associated with drug-drug interactions: data mining of a spontaneous reporting database in Italy.

AIM: To investigate the potential therapeutic effect of exopolysaccharide (EPS)-producing Streptococcus thermophilus (S. thermophilus) CRL 1190 fermented milk on chronic gastritis in Balb/c mice.

METHODS: Balb/c mice were fed with the fermented milk for 7 d after inducing gastritis with acetyl-salicylic acid (ASA, 400 mg/kg body weight per day for 10 d). Omeprazole was included in this study as a positive therapeutic control. The gastric inflammatory activity was evaluated from gastric histology and inflammation score, number of interleukin-10 (IL-10), interferon-γ (INFγ) and tumor necrosis factor-α (TNF-α) cytokine-producing cells in the gastric mucosa, and thickness of the mucus layer.

RESULTS: Animals receiving treatment with the EPS-producing S. thermophilus CRL 1190 fermented milk showed a conserved gastric mucosa structure similar to that of healthy animals. Inflammation scores of the fermented milk-treated mice were lower than those of mice in the gastritis group (0.2 ± 0.03 vs 2.0 ± 0.6, P < 0.05). A marked decrease in INFγ+ (15 ± 1.0 vs 28 ± 1.2, P < 0.05) and TNF-α+ (16 ± 3.0 vs 33 ± 3.0, P < 0.05) cells and an increase in IL-10+ (28 ± 1.5 vs 14 ± 1.3, P < 0.05) cells compared to the gastritis group, was observed. Also, an increase in the thickness of the mucus gel layer (2.2 ± 0.6 vs 1.0 ± 0.3; 5.1 ± 0.8 vs 1.5 ± 0.4 in the corpus and antrum mucosa, respectively, P < 0.05) compared with the gastritis group was noted. A milk suspension of the purified EPS from S. thermophilus CRL1190 was also effective as therapy for gastritis.

CONCLUSION: This study suggests that fermented milk with S. thermophilus CRL 1190 and/or its EPS could be used in novel functional foods as an alternative natural therapy for chronic gastritis induced by ASA.

Therapeutic effect of Streptococcus thermophilus CRL 1190-fermented milk on chronic gastritis.

Background Multiple drugs therapies may be the potential source of drug–drug interactions that can result in alteration of therapeutic response and/or increase untoward effects of many drugs. Objective To identify the frequency and levels of potential drug–drug interactions (pDDIs) in internal medicine wards and their association with patients’ age, gender, length of hospital stay and number of prescribed medications; and to describe management of frequently identified major or moderate pDDIs. Setting Internal medicine wards of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. Method Micromedex Drug-Reax system was used to screen patient’s profiles for pDDIs. Logistic regression was applied to determine the odds ratio for specific risk factors of pDDIs i.e., age, gender, hospital-stay and number of medications. Main outcome measure Overall prevalence and prevalence of contraindicated, major, moderate and minor pDDIs; levels of pDDIs; frequently identified major or moderate interactions; and odds ratios for risk factors. Results Total, 188 interacting drug-combinations were identified that contributed to 675 pDDIs. Of 400 patients, 52.8 % patients were presented with at least one pDDI (overall prevalence), 21.3 % with at least one major-pDDI, and 44.3 % with at least one moderate-pDDI. Of 675 pDDIs, most were of moderate (63.6 %) or major severity (23 %); good (61.2 %) or fair (25.5 %) type of scientific evidence; and delayed onset (50.2 %). Most frequently identified major or moderate interactions resulted in 45.3 % of all pDDIs. Their potential adverse outcomes included hepatotoxicity, bleeding, ototoxicity, nephrotoxicity, hypoglycemia, hyperglycemia, risk of thrombosis, hypotension, cardiac arrhythmias and reduction in therapeutic-effectiveness. There was significant association of the occurrence of pDDIs with patients’ age of 60 years or more (OR = 2.1; 95 % CI = 1.3–3.3; p = 0.003), hospital stay of 6 days or longer (OR = 2.6; 95 % CI = 1.5–4.5; p = 0.001), and seven or more number of prescribed medications (OR = 5.9; 95 % CI = 3.6–9.6; p < 0.001). Conclusion The present study has recorded a high prevalence of pDDIs in internal medicine wards. Patients with old age, longer hospital stay and increased number of prescribed medications were at higher risk.

Potential drug–drug interactions in internal medicine wards in hospital setting in Pakistan

Aim
To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence.

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Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study.

Resumen Objetivos Determinar la prevalencia de interacciones medicamentosas en pacientes pluripatologicos polimedicados y los factores asociados. Como objetivo secundario determinamos la aceptacion de un programa de notificacion de interacciones medicamentosas con recomendaciones dirigido a los facultativos prescriptores. Sujetos y metodos Estudio transversal en 3 centros de salud del area sanitaria de un hospital universitario. Se incluyeron todos los pacientes pluripatologicos a quienes se les habia recomendado 5 o mas farmacos diferentes de forma simultanea. Las interacciones medicamentosas se detectaron mediante el programa Drug-Reax System® (Micromedex), Bot del Consejo General de Colegios Oficiales de Farmaceuticos de Espana, o mediante busqueda bibliografica. Fueron seleccionadas como relevantes aquellas interacciones medicamentosas consideradas por los investigadores farmaceuticos como susceptibles de intervencion. La aceptacion del programa de notificacion de interacciones medicamentosas se evaluo mediante una encuesta dirigida a los facultativos de atencion primaria («aceptable», recomendacion oportuna que potencialmente puede modificar el tratamiento). Resultados Fueron incluidos 283 pacientes pluripatologicos polimedicados, con una edad media de 74,5 anos (rango 43–100 anos). La media de condiciones patologicas por paciente fue de 2,5 y de prescripciones de 9,7. De un total de 2.748 prescripciones medicamentosas se identificaron 1.053 interacciones medicamentosas que afectaron a 250 enfermos (96,5%). Se consideraron interacciones relevantes el 45%. La presencia de cardiopatia isquemica, haber estado ingresado en 2 o mas ocasiones y recibir 7 o mas prescripciones se asocio con la presencia de interacciones medicamentosas. Desde el servicio de farmacia se emitieron 177 notificaciones para otros tantos facultativos responsables de cada paciente que contenian 473 recomendaciones sobre las interacciones detectadas. Un 72% de las recomendaciones ofrecidas desde Farmacia fueron respondidas y se consideraron «aceptables» el 84% de estas. Conclusiones Casi la totalidad de los pacientes pluripatologicos polimedicados estan expuestos a interacciones medicamentosas y de ellas, aproximadamente un 60% requiere alguna intervencion. La notificacion personalizada de interacciones a los medicos de atencion primaria es aceptada y puede ser una accion estrategica que mejore el cociente beneficio riesgo de la prescripcion farmacologica.

Interacciones medicamentosas en pacientes pluripatológicos

https://revistafarmaciahospitalaria.sefh.es/gdcr/index.php/fh/article/download/797/797

M. Alcalá

Papers

Interacciones medicamentosas en pacientes de un servicio de medicina interna

[Drug-drug interactions in patients from an internal medicine service].