Actual Drug-drug Interactions Research Articles

Adverse drug reactions and correlations with drug-drug interactions: A retrospective study of reports from 2011 to 2020.

Introduction: Adverse drug reactions (ADRs) represent a public health problem worldwide that deserves attention due to the impact on mortality, morbidity, and healthcare costs. Drug–drug interactions (DDIs) are an important contributor to ADRs. Most of the studies focused only on potential DDIs (pDDIs), while the detailed data are limited regarding the ADRs associated with actual DDIs. Methods: This retrospective study evaluated ADRs reported between 2011 and 2020 in a tertiary hospital. The causality and severity of ADRs were evaluated through the Naranjo Algorithm and Hartwig’s scale, respectively. Preventability classification was based on the modified Schoumock and Thornton scale. For ADRs with at least two suspected drugs, pDDIs were identified according to the Lexi-Interact. We further checked whether the ADR description in the reports corresponded to the clinical consequences of the pDDIs. Results: A total of 1,803 ADRs were reported, of which 36.77% ADRs were classified as mild, 43.26% as moderate, and 19.97% as severe. The assessment of causality showed that the distributions of definite, probable, and possible categories were 0.33%, 58.68%, and 40.99%, respectively. A total of 53.97% of ADRs were identified as preventable ADRs, while 46.03% were recognized as unpreventable. The severity of ADRs was significantly correlated with age, the number of suspected drugs and preventability. Antimicrobial agents were the most common implicated pharmacological group, and the most frequently affected system was the gastrointestinal system. Considering individual drugs, aspirin was the most frequently reported drug. Among 573 ADRs with at least two suspected drugs, 105 ADRs were caused by actual DDIs, of which only 59 and 6 ADRs were caused by actual DDIs in category D and X, respectively. The most frequent drugs involved in actual DDIs of category D were aspirin and heparin, with the majority of ADRs being gastrointestinal bleeding. Conclusion: This study analyzed the pattern of ADRs in detail and obtained clinical evidence about ADRs associated with actual DDIs. These findings may be useful to compare patterns between different centers and to design preventive strategies for ADRs. Continuous education and training should be provided for physicians regarding the knowledge and recognition of ADRs associated with DDIs.

Investigating Potential Drug-Drug Interactions from Greek e-Prescription Data.

The prevalence of potential drug-drug interactions (pDDIs) is indicative of the prevalence of actual drug-drug interactions and prescription quality. However, they are significantly understudied in Greece. The objective of the study was to determine the prevalence of pDDIs among outpatients and identify factors associated with their occurrence. Anonymous e-prescription data between 2012 and 2017 were obtained from community pharmacies in Thessaloniki, Greece. Patients taking more than one medication for at least three months were included. pDDIs were identified and categorized depending on their clinical significance using Drug Interactions Checker. Crude and adjusted odds ratios (ORs) with accompanying 95% confidence intervals (CIs) of risk factors of pDDIs occurrence were identified using multivariable logistic regression. During the study period, 6,000 anonymous e-prescriptions (1,000 per year) satisfying the inclusion criteria were collected. The overall prevalence of major pDDIs was 17.4% (63.0% for moderate pDDIs). The most common major pDDIs were between amlodipine and simvastatin (22.8% of major interactions), followed by clopidogrel and omeprazole (6.4% of major interactions). Polypharmacy (≥5 concomitantly received medications) was associated with an increased risk of major pDDIs (adjusted OR, 5.72; 95% CI, 4.87-6.72); no associations were observed regarding age, sex, and number of prescribing physicians. The prevalence of pDDIs in this study was higher than previously reported in other European countries, with polypharmacy being a potential risk factor. Those results argue for a need for improvement in the area of prescribing in Greece.

Assessment of drug-drug interactions among patients with psychiatric disorders: A clinical pharmacist-led study

BackgroundDrug-drug interaction alters the efficacy of the drugs. Early identification can reduce unintended therapeutic outcomes. ObjectiveThe main objective of the present study was to assess the drug-drug interactions among patients with psychiatric disorders. MethodologyA prospective observational study was conducted for a period of eight months. A total of 112 psychiatric inpatients were enrolled in the study. The patients were monitored regularly to identify the incidence of potential and actual drug-drug interactions. The identified interactions were analyzed for their severity by using various standard references which included published scientific articles, online databases (e.g., UpToDate) and standard textbooks. Results and DiscussionThe mean age of the study population in years was found to be 37.93 ± 12.21 standard deviation. It was observed that the incidence of potential drug-drug interactions was 66.96%. A total of 201 potential drug-drug interactions were identified from 75 patients. Based on the severity assessment of the identified interactions, 52.73% were major, 37.31% were moderate, and 19.82% were minor. About 7.46% were contraindicated drug combinations. The data on the onset of interaction revealed that 34.82% were of delayed onset and 14.92% with rapid onset and 50.24% were not specified. The drug that was responsible for the majority of the interactions in the study was found to be olanzapine. ConclusionThe study revealed a high incidence of drug-drug interaction. Drug-drug interactions most frequently encountered among psychiatric patients were found to be major in terms of severity. The study concluded on the higher event of drug-drug interactions among the patients prescribed with olanzapine.

Mechanisms and Consequences of Drug‐Drug Interactions

Medications used to treat human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections present a special challenge with respect to the management of potential and actual drug-drug interactions (DDIs). The HIV and HCV treatments may interact with each other, and also interact with drugs of abuse and/or with medications used to treat substance abuse. Possible mechanisms of these DDIs generally include induction or inhibition of activity/expression of human cytochromes P450, glucuronosyl transferases, or energy-dependent transport proteins. These DDIs can be complex and time-dependent in nature. Because time and resources available for new drug development are necessarily limited, not all potential DDIs can be evaluated via clinical pharmacokinetic studies in the course of development of HIV, HCV, and substance abuse treatments. Strategies are needed to refine existing in vitro models and screening techniques to allow more efficient targeting of resources to those clinical studies having the highest impact in terms of enhancing medication effectiveness and patient safety.

Expected and actual adverse drug-drug interactions in elderly patients accessing the emergency department: data from the ANCESTRAL-ED study

ABSTRACTObjective: This study was aimed at evaluating the frequency and describing the adverse drug-drug interactions (DDIs) recorded among elderly patients accessing the emergency department (ED).Methods: Patients aged ≥65 years, accessing the ED of Pisa University Hospital (Italy) from 1 January 2015 to 31 December 2015 within the ANCESTRAL-ED program, were included in this study. ‘Expected’ DDIs were assessed using Thomson Micromedex®. Each ED admission (discharge diagnosis) consistent with the signs and symptoms of an expected DDI for each patient was classified as an ‘actual’ DDI.Results: Throughout the study period, 3473 patients (3812 ED admissions, 58% females, mean age: 80.3) were recorded. The total number of expected DDIs was 12,578 (67 contraindicated; 3334 major; 8878 moderate; 299 minor) detected in 2147 (62%) patients. Overall 464 expected DDIs were found to be consistent with the ED admission in 194 patients (representing 9% of patients with expected DDIs).Conclusions: More than one half of elderly patients admitted to ED presented at least one expected DDI at the time of ED presentation. However, 9% of the expected DDIs were identified as actual DDIs, based on the consistency of the expected event with the ED discharge diagnosis.

Hospital admissions/visits associated with drug–drug interactions: a systematic review and meta‐analysis

To estimate prevalences of hospital admissions/visits associated with actual drug-drug interactions (DDIs) and examine the effect of study design (prospective vs. retrospective), population (all ages or adults), and method of detecting DDIs on reported prevalences. PubMed, International Pharmaceutical Abstracts, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature plus, and the Cochrane Database of Systematic Reviews up to October 2013 were searched for observational studies examining actual DDIs, in any language. The outcomes in this study were DDI prevalence rates in total populations, DDI prevalence rates in total adverse drug reaction patients, and frequency (%) of each pair of DDIs. Thirteen studies met our inclusion criteria. The median DDI prevalence rate for hospital admissions was 1.1% (367 DDI cases/47 976 patients, interquartile range [IQR] 0.4-2.4%). The median DDI prevalence rate for hospital visits was 0.1% (20 DDI cases/23 607 patients, IQR 0.0-0.3%). In adverse drug reaction patients, the median DDI prevalence rate for hospital admissions (308 DDI cases/1683 patients) and hospital visits (8 DDI cases/90 patients) were 22.2% (IQR 16.6-36.0%) and 8.9%, respectively. Medical record, interview, drug interaction screening program, adverse reaction report, and electronic medical record were identified as methods used for detecting DDIs. Non-steroidal anti-inflammatory drugs were most commonly involved in hospital admission associated DDIs, whereas warfarin was frequently involved in DDIs detected at hospital visits as outpatients/emergencies. Drug-drug interactions are a significant cause of hospital admissions and hospital visits. Improved DDI information gathering could help to reduce such adverse effects from DDIs, especially for patients using non-steroidal anti-inflammatory drugs and warfarin.

Actual drug–drug interactions in elderly patients discharged from internal medicine clinic: a prospective observational study

The aim of the study was to evaluate the incidence and type of actual drug-drug interactions (DDIs) that result in adverse drug reactions (ADRs) or diminished therapeutic effect in elderly patients within 30 days of discharge from an internal medicine clinic. A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between October and December 2011. Patients aged ≥ 65 years discharged from the Internal Medicine Clinic during the study period with a prescription for two or more medications were eligible for inclusion in the study. A total of 222 patients were ultimately enrolled in the study. For each patient, potential DDIs were identified using Lexi-Interact software. The follow-up visit was scheduled approximately 30 days after discharge. Causality between DDIs and ADRs or diminished therapeutic effect of drugs was assessed by two independent clinicians. Potential DDIs were identified in 190 (85.6 %) patients. Actual DDIs were detected in 21 (9.5 %) patients. In 19 patients, DDIs resulted in an ADR. Diminished therapeutic effect resulting from DDIs was detected in two patients. Angiotensin-converting enzyme inhibitors were the drug class most frequently associated with DDI-related ADRs. A significant incidence of actual DDIs suggests that DDIs play an important role in patient safety. Drug therapy should be initiated if absolutely necessary, and the number of drugs used to treat elderly patients should be minimized to reduce the incidence of DDI-related adverse patient outcomes.

Rilevanza clinica e aspetti medico-legali delle interazioni tra farmaci

[ Clinical relevance and medical legal aspects of drug-drug interactions] Drug-drug interactions (DDIs) are an important issue of clinical pharmacology. A drug interaction occurs when the amount or the action of a drug is altered by the administration of another drug or multiple drugs. The result of a DDI can be the onset of an adverse drug reaction (ADR), the lack or the reduction of efficacy or the increase of a pharmacological effect. Apart from pharmaceutical interactions, DDIs are generally classified as pharmacokinetic or pharmacodynamic, according to the underlying mechanism. The majority of known DDIs involve the drug metabolism. The main risk factors for DDIs are age, polypharmacy, self-medication, concomitant diseases, narrow therapeutic range and dosage. In the literature most of the studies on DDIs focused on potential interactions and most data about the epidemiology of actual DDIs are related to the out-inpatient settings with different incidences. In general the incidence of actual DDIs is lower than that of potential ones, however DDIs represent a significant proportion of ADRs, since the absolute number of patients involved is high. The use of specific suggestions and recommendations could be effective in the reduction of ADRs from DDIs.

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

AimTo 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.MethodsIn this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them.ResultsHALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter.ConclusionThe study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education.