Occurrence Of Potential Drug-drug Interactions Research Articles

The inadvertent consequences of drug recalls: A case study of a recall of pantoprazole generics from the markets

IntroductionDrug recalls may impact treatment plans or access to suitable therapies. Thus, they inadvertently affect treatment outcomes. ObjectiveWe aimed to examine the impact of recalls on patients’ safety using pantoprazole-containing products recall as a case study in terms of the occurrence of potential drug-drug interactions (pDDIs). MethodsThis retrospective study used de-identified electronic health records of adult patients who had a prescription for oral proton pump inhibitors (PPIs) including pantoprazole, esomeprazole, lansoprazole, or omeprazole from April 2020 through September 2021 from a large tertiary care hospital. The study outcome definition was the prevalence of pDDIs in PPIs users before and after the recall date (March 2021). Changes in the prevalence of pDDIs were modeled using interrupted time-series. The rate ratio of pDDIs in the 12 months before and 6 months after the recall was modeled using negative binomial regression. ResultsA total of 1,826 pDDIs were identified, and the median monthly prevalence of pDDI before the recall was 102.5 which increased to 115.5 after the recall. A change in the level of pDDIs occurred immediately after the recall date, followed by a gradual decrease over time. The rate of pDDIs was 69% higher after the recall compared to the baseline (rate ratio 1.69; 95% confidence interval, 0.75–1.91). DiscussionRecall of pantoprazole-containing products was associated with a higher rate of pDDIs. However, the prevalence of pDDIs gradually decreased over time. We highlight the importance of planning of recall process and coordinating all potential stakeholders to avoid potential harms.Word count: 1450.

High prevalence of potential psychotropic drugs interactions among Brazilian dental patients.

To determine the prevalence of potential drug-drug interactions involving psychotropics prescribed by dentists, and dispensed by the public healthcare system, as well as to describe the severity and level of evidence of those interactions in the state of Minas Gerais, Brazil. We conducted data analysis from pharmaceutical claims in which dental patients received systemic psychotropics in 2017. Data from the Pharmaceutical Management System provided the drug dispensing history of the patients, allowing the identification of those on concomitant medication use. The outcome was the occurrence of potential drug-drug interactions, which were detected according to IBM Micromedex®. Independent variables were the patient's sex, age, and the number of drugs used. Descriptive statistics was performed using SPSS v. 26. Overall, 1480 individuals were prescribed psychotropic drugs. The prevalence of potential drug-drug interactions was 24.8% (n=366). The total of 648 interactions was observed and, most of which were of major severity (n=438, 67.6%). Most interactions occurred in female individuals (n=235; 64.2%), with 46.0 (±17.3) years-old, concurrently taking 3.7 (±1.9) drugs. A substantial proportion of dental patients presented potential drug-drug interactions, mostly of major severity, which might be life-threatening.

Potential drug-drug interactions due to concomitant medicine use among people living with HIV on antiretroviral therapy in Australia.

We quantified concomitant medicine use and occurrence of potential drug-drug interactions in people living with HIV in Australia who are treated with antiretroviral therapy (ART). In this cohort study using dispensing claims of a 10% random sample of Australians, we identified 2230 people dispensed ART between January 2018 and December 2019 (mean age 49.0years, standard deviation 12.0years, 88% male). We examined concomitant medicine use by identifying nontopical medicines dispensed within 90-days of any antiretroviral medicine dispensing during a 12-month follow-up period. For every antiretroviral and nonantiretroviral pair, we identified and classified possible drug-drug interactions using the University of Liverpool HIV drug interactions database. A total of 1728 (78%) people were dispensed at least 1 and 633 (28%) 5 or more unique medicines in addition to ART in a 12-month period; systemic anti-infectives and medicines acting on the nervous system were the most common (68% and 56%, respectively). Among comedicated people, 1637 (95%) had at least 1 medicine combination classified as weak interactions, 558 (32%) interactions requiring close monitoring/dose adjustment and 94 (5%) that should not be coadministered. Contraindication or interactions requiring close monitoring/dose adjustment were more common among people receiving protease inhibitors (50-73% across different antiretrovirals), non-nucleoside reverse transcriptase inhibitors (35-64%), people using single-tablet combinations containing elvitegravir (30-46%) and those using tenofovir disoproxil (26-30%). Concomitant medicine use is widespread among people living with HIV in Australia. Despite a relatively low prevalence of contraindicated medicines, almost a third received medicines that require close monitoring or dose adjustment.

High Prevalence of Potential Drug-Drug Interactions Among Patients Treated with Off-label Therapies for COVID-19

Background: During the first wave of the COVID-19 pandemic, severe patients were treated with the off-label drugs hydroxychloroquine and lopinavir/ritonavir. The aim of the study was to determine the prevalence of potential drug-drug interactions (DDIs) between hydroxychloroquine, lopinavir/ritonavir and concomitant medications used by hospitalized patients treated for COVID-19 in Costa Rica.
 Methods: We included all patients that received lopinavir/ritonavir or hydroxychloroquine as treatment for COVID-19. Clinical pharmacists reviewed the prescription profile of each patient and determined the probability and severity of any DDI through two databases (The Lexi-Interact program) and the Micromedex online interaction checker. A logistic regression model was used to identify variables associated with the occurrence of potential DDIs.
 Results: We identified a total of 108 potential DDIs in 34 inpatients (n=34). At least one of these DDIs occurred in 27 patients (79.4%; 95% CI: 65.8-92.9%). A total of 70 DDIs (64.8%) were classified as clinically relevant (grade D or X) by the clinical pharmacists. Only the number of concomitant drugs was associated with the occurrence of a probable DDI. The most common drugs associated with any DDI were fentanyl (n=12, 11.1%), midazolam (n=11, 10.2%), and insulin (n=10, 10.2%).
 Conclusion: A large proportion of patients treated with hydroxychloroquine and lopinavir/ritonavir for severe COVID-19 were at risk for clinical meaningful DDIs.

Drug-drug interactions in atrial fibrillation patients receiving direct oral anticoagulants

Polypharmacy is common in patients with atrial fibrillation (AF), making these patients vulnerable to the occurrence of potential drug-drug interactions (DDIs). We assessed the risk of ischemic stroke and major bleeding in the context of concomitant treatment with potential DDIs in patients with AF prescribed direct oral anticoagulants (DOACs). Using the common data model (CDM) based on an electronic health record (EHR) database, we included new users of DOACs from among patients treated for AF between January 2014 and December 2017 (n = 1938). The median age was 72 years, and 61.8% of the patients were males, with 28.2% of the patients having a CHA2DS2-VASc score in category 0–1, 49.4% in category 2–3, and 22.4% in category ≥ 4. The CHA2DS2-VASc score was significantly associated with ischemic stroke occurrence and hospitalization for major bleeding. Multiple logistic regression analysis showed that increased risk of ischemic stroke and hospitalization for major bleeding was associated with the number of DDIs regardless of comorbidities: ≥ 2 DDIs was associated with ischemic stroke (OR = 18.68; 95% CI, 6.22–55.27, P < 0.001) and hospitalization for major bleeding (OR = 5.01; 95% CI, 1.11–16.62, P < 0.001). DDIs can cause reduced antithrombotic efficacy or increased risk of bleeding in AF patients prescribed DOACs.

Risk Factors for the Occurrence of Potential Drug-Drug Interactions in Surgical Patients

Abstract Background: Drug-drug interactions are defined as modifications of the drug action that result from the simultaneous administration of another individual drug or several drugs. Nowadays, potential drug-drug interactions (DDIs) are most frequently detected and analyzed using personal digital assistant software programs (online interaction checker tools). Objective: To determine the risk factors for the emergence of all drug-drug interactions in surgical patients with particular emphasis on clinically significant interactions. Patients and methods: This was a retrospective cohort analysis of patients treated at the Surgical Clinic of the Clinical Center Kragujevac. Three interaction checkers were used to reveal drug-drug interactions: Medscape, Epocrates and Micromedex. Results: The study included total of 200 patients, aged 58.54±17.08 years. Average number of drug-drug interactions per patient was between 10.50±9.10 (Micromedex) and 18.75±17.14 (Epocrates). Number of prescribed drugs, antidepressive therapy, antiarrhythmic therapy, number of pharmacological/therapeutic subgroups (2nd level of ATC classification) prescribed, delirium or dementia, diabetes, heart failure, and number of physicians who prescribed drugs to single patient were identified as risk factors for drug-drug interactions while length of hospitalization in days and age of patient in years emerged as protective factors. Conclusion: Drug-drug interactions are relatively common in surgical patients and predisposed by factors such as number of prescribed drugs or drug group per patient, number of physicians who prescribed drugs, antidepressive therapy, antiarrhythmic therapy, presence of delirium or dementia, diabetes and heart failure. On the other hand, prolonged hospitalization and higher age are factors that reduce the risk of interactions in surgical patients.

Risk factors for potential drug-drug interactions in patients with pneumonia

The goal of our study was to discover and analyze possible risk factors for and possible protective factors against the occurrence of potential drug-drug interactions (pDDIs) in a hospitalized patient with community-acquired pneumonia. The central outcome was the incidence of pDDIs in patients with community-acquired pneumonia checked by Lexicomp and Micromedex interaction checkers. The most severe pDDIs (Consider therapy modification D/Avoid combination X/Major/Contraindicated) were found in 19 (20%) and 54 (58%) patients, according to Lexicomp and Micromedex, respectively. Patients with community-acquired pneumonia who were older, smokers, and with more prescribed drugs by more than a few independent prescribers had a higher risk to experience pDDIs. Possible protective factors were longer length of hospitalization, transfer from the Emergency Department, antiarrhythmic drugs as well as an anticoagulant therapy. In conclusion, community-acquired pneumonia patients with the above-mentioned factors should have their treatment more deeply monitored for pDDIs.

The role of the clinical pharmacist in the prevention of potential drug interactions in geriatric heart failure patients.

Background The treatment of heart failure patients is very complex and includes lifestyle modification as well as different pharmacological therapies. Polypharmacy is very common in such patients and they are at increased risk of potential drug-drug interactions and associated effects such as poor adherence, compliance and adverse events. Objective The aim of the present study is to investigate retrospectively the prescribed pharmacotherapy of the hospital discharged heart failure patients for possible drug interactions. Settings Clinic for Cardiology of the "Saint Marina" University Hospital in Varna, Bulgaria. Method Lexicomp® Drug interaction software was used for screening potential drug-drug interactions. Logistic regression was applied to determine the odds ratio for the association between the age and number of drugs taken and the number of potential drug-drug interactions. Main outcome measure Incidence and type of pDDIs in geriatric heart failure patients. Results A retrospective study was conducted by reviewing the medical records of 248 selected heart failure patients for the prescribed medicines for a 1-year period (January 2015-December 2015). The total number of potential drug-drug interactions was 1532, or approximately 6.28 (± 4.72 SD) per one person. The range of prescribed drugs was between three and fourteen, 92% of them have been taking more than five medicines, an average of 7.12 (± 2.07 SD) per patient. The average age was 72.35 (± 10.16 SD). The results have shown stronger association between the number of drugs taken (more than 7) and the occurrence of potential drug-drug interactions (more than 10)-37.84 (95% CI 9.012-158.896, P ≤ 0.001). No statistically significant differences were found between age and occurrence of potential drug-drug interactions (more than 10)-1.008 (95% CI 0.441-2.308, P = 0.848). Conclusion The incidence of drug-drug interactions in heart failure patients is high. The clinical pharmacist, as a part of the multidisciplinary team, could reduce medication-related problems, such as drug interactions, and to optimize drug therapy by checking the treatment prescribed at the discharge of these patients.

Prevalence of potential drug-drug interactions in Swedish pediatric outpatients.

PurposeTo describe the occurrence of potential drug-drug interactions (DDIs) in prescribed drugs, dispensed to pediatric outpatients in Sweden.MethodsA cross sectional study was conducted based on data from a national register of prescribed drugs, dispensed at pharmacies, to children 0–17 years old. The study period was January 1 to April 30, 2010. Drug dispensing data was linked to the DDI database SFINX. Prevalence and frequencies of potential interactions were investigated, and drugs commonly involved in interactions were identified. The study focused on clinically relevant potential interactions, class D (should be avoided), and class C (can be handled, e.g. by dose adjustment).ResultsIn the Swedish pediatric population, 0 to 17 years of age, 12% (n = 231 078) of children had at least two dispensed drugs. In this group of patients, 0.14% had potential D-interactions and 1,3% had potential C-interactions. The number of D- and C-interactions that may lead to reduced effects were 181 (52%), and 1224 (32%) respectively. The ten most frequent drugs were involved in 78% and 65% of all potential D-, and C-interactions respectively. Furthermore, 80%, and 58% of the D-, and C-interactions respectively occurred in patients aged 12 to 17.ConclusionsWe identified a limited number of drugs that were represented in the majority of potential interactions. Interactions that can lead to a reduced treatment effect constituted approximately half of D-interactions, and a third of C-interactions. The frequency of potential interactions was higher in older children. The results may contribute to increased prescriber awareness of important potential drug interactions among pediatric outpatients.

Factors associated with drug interactions in elderly hospitalized in high complexity hospital.

This study aims to determine the frequency of potential drug-drug interactions (PDI) in hospitalized elderly and associated factors. This is a cross-sectional study in a teaching hospital. The dependent variable was the occurrence of potential drug interactions identified using DrugReax software. Patients with adverse drug reactions (ADR) related to clinical manifestations of PDIs were also identified. Multivariate logistic regressions was performed to analyze the association between the occurrence of PDIs and independent variables. In total, 237 older adults were included in the study. The prevalence of PDIs and interaction-related ADRs was 87.8% and 6.8%, respectively. The multivariate analysis showed a positive association between the detection of PDIs (OR 8.6; 95% CI, 2.5-30.0), and hospitalization due to a diagnosed circulatory system disease and number of medications > 14 (OR 9.8; 95% CI, 2.8-34.3%). The study showed a high prevalence of PDIs in the drug treatment of the elderly, but a lower prevalence of ADRs, as well as a positive association between PDIs and hospitalization due to a diagnosed circulatory system disease and number of medications > 14. The identification of factors associated with PDIs guides prevention measures for people that are more exposed to adverse events.

Potential drug–drug interactions in pediatric wards of Gondar University Hospital, Ethiopia: A cross sectional study

ObjectiveTo determine the prevalence, level of severity of potential drug–drug interactions (PDDIs) and the associated factors for PDDIs in hospitalized pediatric patients of Gondar University Hospital. MethodsA retrospective cross-sectional study was conducted for a period of 3 months from March to May 2014 in pediatric wards of Gondar University Hospital. Systematic random sampling technique was used to select charts from all pediatric patients' charts with every 7th interval to get sample size of 384. Univariate and multivariate analysis were performed to compute crude odds ratio and adjusted odds ratio respectively. Statistical significance was set at P value < 0.05. ResultsA total of 176 (45.8%) patients had at least one PDDI. A total of 393 PDDIs, which were comprised of 283 types of interacting combinations, were identified. Of the total of 393 PDDIs, most were of moderate severity [201 (51%)] followed by minor [152 (39%)] and major severity [40 (10%)]. The most common interacting pairs of major severity were gentamicin + furosemide (6), cotrimoxazole + methotrexate (4) and phenytoin + artemether (4). The occurrence of PDDIs was significantly associated with age and polypharmacy. ConclusionsThe study showed that most of the interactions had moderate severity followed by minor severity. Age and polypharmacy were found to show statistically significant association with the occurrence of PDDIs. Due to sensitive nature of pediatrics population, close monitoring is recommended for the detection and management of PDDIs to prevent its negative consequences.

Assessment of potential drug-drug interactions among outpatients receiving cardiovascular medications at Jimma University specialized hospital, South West Ethiopia

Background: The quality of pharmacotherapy is highly dependent on the process of choosing a drug in relation to nature of the disease. Several factors should be considered in choosing optimal pharmacotherapeutics strategy including efficacy, safety, availability and cost of the drugs. The objective of this study was to assess potential drug-drug interactions and risk factors in outpatients taking cardiovascular drugs at Jimma University specialized hospital. Methods: A cross-sectional study was conducted from Feb. to April, 2011on patients visiting the cardiac clinic of Jimma University Specialized hospital. A sample of 332 outpatients who were taking cardiovascular medications at study clinic was studied. MicroMedex software was used to screen drug-drug interactions and SPSS for windows software versions-16.0 was used for data analysis. Results: A total of 1249 drugs with average of 3.76 drugs per prescription were prescribed for the 332 patients. The frequency of potential DDIs was found to be 241 (72.6%). Among these 200 (67.3%) were of "moderate" severity and 164 (55.2%) were delayed in onset. The most common potential DDI observed was between Enalapril and Furosemide (20%). Patients who prescribed many drugs (AOR=4.09; P=0.00) by medical intern had a higher risk of developing potential DDIs (AOR=4.6; P=0.00). Conclusions: Patients with cardiovascular disorders are subjected to high risk of potential drug-drug interactions and the number of drugs prescribed and educational level of the prescribers has a high significantly associated with the occurrence of potential drug-drug interactions. Therefore, it is imperative that further studies need to be conducted to identify reasons for and tackle the problem and provide appropriate mechanisms for management.

Occurrence of potential drug-drug interactions in nursing home residents

Abstract Objective It has been suggested that elderly people are at increased risk of drug-related problems such as drug-induced adverse effects, drug-drug interactions and drug-disease interactions. This is particularly the case for nursing home residents because of the often complicated and multiple co-morbidity that occurs in these people. The aim of this study was to develop prescribing indicators to assess systematically the occurrence and nature of potential drug-drug interactions (DDIs) in a cohort of Dutch nursing home residents. Method The study was conducted in residents aged 65 years and over in six nursing homes (n=2,355, two-year study period). Computerised medication data for the residents were evaluated with respect to co-prescribing of potentially interacting drugs. All DDIs that were classified as clinically relevant according to the Dutch National Drug Interaction Database were studied. DDIs were classified into three categories according to their pharmacological mechanism: 1 — pharmacokinetic interactions at the level of gastrointestinal (GI) absorption; 2 — pharmacokinetic interactions at the level of metabolism and excretion; and 3 — pharmacodynamic interactions. Key findings Thirty-two per cent (n=748) of all residents were exposed to one or more combinations of drugs that could lead to clinically adverse outcomes. The numbers of residents who received drug combinations with a mechanism of interaction from category 1, 2 or 3 were 73 (3 per cent), 164 (7 per cent) and 612 (26 per cent) respectively. The number of medications prescribed was significantly associated with the occurrence of a potential DDI (P&amp;lt;0.05). Drugs most frequently involved were oral anticoagulants, antibiotics and theophylline. Conclusion During the two-year study period, about one-third of the residents were exposed to at least one drug interaction considered clinically relevant. Adequate surveillance systems are needed to enable better identification of these interactions with a view to preventing potential clinical problems. Using the prescribing indicators developed in this study, such surveillance could focus on detection and clinical aspects of potential DDIs and possible alternative treatments.

Laboratory Tests in the Clinical Risk Management of Potential Drug-Drug Interactions

Patient safety and the life cycle of a drug are negatively influenced by the still increasing occurrence of potential drug-drug interactions (DDIs). Clinical risk management of potential DDIs is required in patients using drugs to influence the benefit-risk profile positively. Information about laboratory test results, in particular, may be useful in the assessment of potential DDIs for the individual patient. The objective of this study was to examine the frequency and nature of laboratory tests required for the assessment of the clinical relevance of potential DDIs in Dutch community pharmacies. In addition, the nature and clinical relevance of these potential DDIs is analysed. All patients from 100 Dutch community pharmacies using, according to dispensing information, two or more drugs concomitantly on a specified date (Wednesday, 4 April 2007), were included (n = 223,019). The anonymous dispensing data of the included patients were analysed against a list of DDIs requiring laboratory tests for the assessment of their clinical relevance. The number of patients at risk for these potential DDIs with severe adverse reactions was calculated. The frequency of potential DDIs requiring laboratory tests were stratified by age, sex and degree of polypharmacy. Of the included patients, 24.4% had one or more potential DDIs (n = 54,427). In 9.0% of the included patients, one or more laboratory tests for the assessment of clinical relevance of the potential DDI were required (n = 19,968). The frequency of DDIs requiring laboratory tests increased with increasing age and number of drugs, but was not related to sex. The most commonly required laboratory tests were for renal function (42.2%), electrolytes (20.1%) and coagulation (13.1%). The percentage of patients at risk for potential DDIs requiring laboratory tests with adverse reaction category F (serious, irrecoverable disablement or death) was 2.5%; category E (increased risk of failure of life-saving therapy) was 0.6%; and category D (inconvenience with residual symptom and failure of therapy concerning serious but non-fatal diseases) was 3.8%. A large number of patients in Dutch community pharmacies are at risk for potential DDIs requiring laboratory tests for the assessment of the clinical relevance of the interaction. There is a strong relationship between the frequency of DDIs requiring laboratory tests and age and the number of drugs concomitantly used. In the clinical risk management of potential DDIs, information about laboratory test results is of additional value. Future research is necessary in order to obtain more evidence on using laboratory tests in terms of which tests should be linked to pharmacy data, in which patients they should be done, how often and what actions should be taken when an abnormal value is found.

Potential drug–drug interactions with antiepileptic drugs in Medicaid recipients

The frequency of potential drug-drug interactions (DDIs) between antiepileptic drugs (AEDs) and other (non-AED) medications in Medicaid patients taking newer AED monotherapy, older AED monotherapy, and combinations of AED treatment was studied. A retrospective, observational study was conducted using administrative claims obtained from South Carolina Medicaid. Patients were included in the analysis if they (1) had at least one prescription for an AED between January 1, 2004, and December 31, 2004, (2) were taking a specific AED for at least 60 days, (3) had at least one epilepsy diagnosis during the 6 months before or during the enrollment period, and (4) were enrolled in Medicaid for at least 11 of the 12 months of the follow-up period. Possible DDI exposure was defined as 10 days of overlap between an AED and a non-AED known to have the potential to cause a clinically relevant interaction. A total of 4955 patients met the inclusion criteria. Approximately 45% of patients receiving monotherapy with an older AED had a potential DDI, compared with 3.9% receiving a newer AED. An average of 0.08 potential DDI per year of exposure occurred in the newer AED monotherapy cohort compared with 1.18 in the older AED monotherapy cohort. The most common potential interaction category was a decreased concentration of the non-AED. Older AEDs were associated with a greater likelihood of a potential DDI than were newer AEDs. Further research is needed to elucidate the relationship between the occurrence of potential DDIs and actual clinically relevant consequences.