Rate Of Drug-drug Interactions Research Articles

Wiring Between Close Nodes in Molecular Networks Evolves More Quickly Than Between Distant Nodes.

As species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction (PPI) networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high-throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in PPI and cofunctional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.

Ritonavir: 25 Years' Experience of Concomitant Medication Management. A Narrative Review.

Ritonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme and is commonly used as a pharmacokinetic (PK) enhancer in antiviral therapies because it increases bioavailability of concomitantly administered antivirals. Decades of experience with ritonavir-enhanced HIV therapies and, more recently, COVID-19 therapies demonstrate that boosting doses of ritonavir are well tolerated, with an established safety profile. The mechanisms of PK enhancement by ritonavir result in the potential for drug-drug interactions (DDIs) with several classes of drugs, thus making co-medication management an important consideration with enhanced antiviral therapies. However, rates of DDIs with contraindicated medications are low, suggesting these risks are manageable by infectious disease specialists who have experience with the use of PK enhancers. In this review, we provide an overview of ritonavir's mechanisms of action and describe approaches and resources available to mitigate adverse events and manage concomitant medication in both chronic and short-term settings.

Prescribed Versus Taken Polypharmacy and Drug-Drug Interactions in Older Cardiovascular Patients during the COVID-19 Pandemic: Observational Cross-Sectional Analytical Study.

The study aimed to assess clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019-2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, the total number of DDIs was significantly higher among the prescribed medications (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among the prescribed and taken medications, respectively (p < 0.05). Median numbers of DDIs between the prescribed vs. taken medications were Me = 2, IQR 0-7 vs. Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among the prescribed medications compared with that among the taken drugs (p < 0.05). Women were taking significantly more drugs and had higher prevalence of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, implement patient engagement in reporting adverse drug reactions, and provide genetic profiling of patients to avoid potentially serious DDIs.

Overriding Drug-Drug Interaction Alerts in Clinical Decision Support Systems: A Scoping Review.

Ineffective computerized alerts for potential Drug-Drug Interactions (DDI) is a longstanding informatics issue. Prescribing clinicians often ignore or override such alerts due to lack of context and clinical relevance, among various other reasons. In this study, we reveiwed published data on the rate of DDI alert overrides and medications involved in the overrides. We identified 34 eligible studies from sites across Asia, Europe, the United States, and the United Kingdom. The override rate of DDI alerts ranged from 55% to 98%, with more than half of the studies reporting the most common drug pairs or medications involved in acceptance or overriding of alerts. The high prevalance of alert overrides highlights the need for decision support systems that take user, drug, and institutional factors into consideration, as well as actionable metrics to better characterize harm associated with overrides.

EVALUATION OF DRUG-DRUG INTERACTIONS IN HOSPITALISED GERIATRIC PATIENTS AT TERTIARY CARE HOSPITAL

A study was planned to evaluate the prevalence, nature, and severity of drug-drug interactions (DDI) in geriatrics. A prospective observational study was carried out in hospitalized patients. DDIs were evaluated using a medscape drug interaction checker. Data of 300 patients were collected who were followed up for 3 days and analyzed over a period of 7 months. The prevalence rate of DDI was 90.3 %, as 271 out of 300 prescriptions showed drug-drug interaction. Out of 300 patients, 4797 possible DDIs were identified, of which 39 (0.81 %) were contraindicated, 290 (6.04 %) serious drug interactions, 3312 (68.85 %) significant interactions and 1156 (24.09 %) minor interactions. Out of 4797 possible DDIs, 2962 (62.91 %) were pharmacodynamics. 1835 (37.08 %) were pharmacokinetic type. Antihypertensive class of drug showed potential for DDIs. Total 244 (81.33 %) cases were found with potentially inappropriate medicines(PIM). The prevalence of DDIs in geriatric patients was 90.3 %. Poly pharmacy and multiple associated conditions in the elderly were the major contributing factors for DDIs.

Assessment of inappropriate prescribing of QT interval-prolonging drugs in end-stage renal disease patients in Jordan

Despite the high risk of life-threatening complications due to drug-induced prolongation of the corrected QT interval (QTcP) in patients with end-stage renal disease (ESRD), the safety of QTcP-inducing drugs has rarely been investigated in this patient population. This study aimed to assess the appropriateness of prescriptions for QTcP-inducing drugs and evaluate potential drug–drug interactions (DDIs) in patients with ESRD in Jordan. This study was a retrospective observational study conducted from October 2019 to March 2020 in the outpatient clinics of 36 healthcare facilities across Jordan. A standardized data collection form was developed and used by pharmacy staff to collect data from the electronic databases of these facilities. The targeted population was patients with ESRD, specifically their prescriptions. Micromedex Drug Reax® software was used to check potential DDIs. Data were analysed using SPSS v26 software. The study included 407 patients with ESRD, who were prescribed 954 drugs with a risk of inducing QTcP. Of these, 17.6% were considered inappropriate application, 12.9% inappropriate choice, and 26.4% inappropriate decision. Roughly two-thirds of the dispensed drugs (64.8%) were associated with a DDI, 10.4% of which were major, 29.3% moderate, and 60.3% minor. Predictors for major DDIs were major polypharmacy, type of clinic and geographic location. Predictors for inappropriate prescribing were type of clinic and geographic location. High rates of DDIs and inappropriate prescribing of QTcP-inducing drugs were reported among patients with ESRD in outpatient clinics in Jordan.

An Investigation of Drug-Drug Interaction Alert Overrides at a Pediatric Hospital.

Drug-drug interactions (DDIs) can result in patient harm. DDI alerts are intended to help prevent harm; when the majority of alerts presented to providers are being overridden, their value is diminished. Our objective was to evaluate the overall rates of DDI alert overrides and how rates varied by specialty, clinician type, and patient complexity. A retrospective study of DDI alert overrides that occurred during 2012 and 2013 within the inpatient setting described at the medication-, hospital-, provider-, and patient encounter-specific levels was performed at an urban, quaternary-care, pediatric hospital. There were >41 000 DDI alerts presented to clinicians; ∼90% were overridden. The 5 DDI pairs that were most frequently presented and overridden included the following: potassium chloride-spironolactone, methadone-ondansetron, ketorolac-ibuprofen, cyclosporine-fluconazole, and potassium chloride-enalapril, each with an alert override rate of ≥0.89. Override rates across provider groups ranged between 0.84 and 0.97. In general, patients with high complexity had a higher frequency of alert overrides, but the rates of alert overrides for each DDI pairing did not differ significantly. High rates of DDI alert overrides occur across medications, provider groups, and patient encounters. Methods to decrease DDI alerts which are likely to be overridden exist, but it is also clear that more robust and intelligent tools are needed. Characteristics exist at the medication, hospital, provider, and patient levels that can be used to help specialize and enhance information transmission.

Addressing Antiretroviral Therapy-Associated Drug-Drug Interactions in Patients Requiring Treatment for Opportunistic Infections in Low-Income and Resource-Limited Settings.

An increasing number of human immunodeficiency virus (HIV)-infected patients are achieving virologic suppression on antiretroviral therapy (ART) limiting the use of primary and secondary antimicrobial prophylaxis. However, in low-income and resource-limited settings, half of those infected with HIV are unaware of their diagnosis, and fewer than 50% of patients on ART achieve virologic suppression. Management of comorbidities and opportunistic infections among patients on ART may lead to inevitable drug-drug interactions (DDIs) and even toxicities. Elderly patients, individuals with multiple comorbidities, those receiving complex ART, and patients living in low-income settings experience higher rates of DDIs. Management of these cytochrome P450-mediated, nonmediated, and drug transport system DDIs is critical in HIV-infected patients, particularly those in resource-limited settings with few options for ART. This article critically analyzes and provides recommendations to manage significant DDIs and drug toxicities in HIV-infected patients receiving ART.

Assessment of drug-drug interactions in hypertensive patients at a superspeciality hospital.

Objective:The objective of the study was to assess the incidence and pattern of drug-drug interactions (DDIs) in hypertensive patients by using Micromedex and Medscape databases.Materials and Methods:A prospective observational study was carried out in a superspeciality hospital setting in South India for period of 9 months. Hypertensive patients who admitted into the hospital with the age more than 18 years, received more than 3 drugs per prescription and length of hospital stay for more than 24 hours were included in the study. An appropriate data was collected and assessed for DDIs with the help of Micromedex and Medscape databases.Results:A total of 227 patients were enrolled during the study period. Among the 227 patients, 48 of them developed 53 clinically significant DDIs. Out of 48 patients, most of them were in the age-group of 50–60 years [18 (37.49%)]. The percentage of DDIs were higher in males [30 (62.5%)] compared to females [18 (37.5%)]. The most common drugs responsible for DDIs in the present study were Insulin [18 (33.96%)] followed by Metoprolol [10 (18.86%)], Torsemide [8 (15.09%)], and Hydrochlorothiazide [8 (15.09%)]. The most commonly interacting pairs were Ciprofloxacin-Insulin [6 (11.32%)], followed by Metoprolol-Insulin [4 (7.54%)] and Atenolol-Insulin [4 (7.54%)]. The most common consequences of interacting pairs were reduced serum potassium levels and hyperglycemia.Conclusion:The overall incidence rate of DDIs was found to be 21.14% and the increasing number of co-morbidities (P ≤ 0.003) and polypharmacy (P ≤ 0.002) were the risk factor for the development of significant number of DDIs.

Polypharmacy-induced Drug-Drug Interactions; Threats to Patient Safety

Patient safety is an increasingly recognized challenge and opportunity for stakeholders in improving health care delivery. Because of extensive use of medicines, life expectancy is increasing and elderly as well as comorbidities need polypharmacy, and therefore the risk of drug-drug interactions (DDIs) increases.We searched PubMed and ScienseDirect for epidemiology of articles describing the frequency of potential DDIs published up to 2011 in title, abstract, keywords and text.Studies show that the rate of DDIs both in outpatients and hospitalized patients is high. The elderly, <5 year-old children and women are at higher risks for it. Also, the rate of DDIs in patients who suffer from chronic kidney disease (CKD), cardiovascular disease (CVD) such as heart failure (HF) and hypertension (HTN) and cancers is significant.Physicians, for lowering the risk of DDIs, should take precise drug history, prescribe appropriate and lowest drugs and ultimately counsel with clinical pharmacologist as a key strategy in order to insure the patient safety. This article reviews the existing data concerning this problem to provide an aid for choosing the appropriate drugs and prescribe the most effective with the lowest DDIs for providing patient safety.

Potential drug–drug interactions in pediatric outpatient prescriptions for newborns and infants

ObjectivesTo surveyed the quantities, types, and related information of potential drug–drug interactions (DDIs) and estimate the off-label use percentage of pediatric outpatient prescriptions for newborns and infants from the National Health Insurance Research Database (NHIRD) of Taiwan. BackgroundAdverse drug reactions (ADR) may cause morbidity and mortality, potential drug–drug interactions (DDI) increase the probability of ADR. Research on ADR and DDI in infants is of particular urgency and importance but the related profiles in these individuals are not well known. MethodsAll prescriptions written by physicians in 2000 were analyzed to identify potential DDIs among drugs appearing on the same prescription sheet. ResultsOf a total of 150.6 million prescription sheets, with 669.5 million prescriptions registered in the NHIRD of Taiwan, six million (3.99%) prescription sheets were for 2.1 million infants with 19.4 million (2.85%) prescriptions. There were 672,020 potential DDIs in this category, accounting for 3.53% per prescription; an estimated one DDI in every three patients. The interactions between aspirin and aluminum/magnesium hydroxide were most common (4.42%). Of the most significant drug–drug interactions, the interaction of digoxin with furosemide ranked first (20.14%), followed by the interactions of cisapride with furosemide and erythromycin (6.02% and 4.85%, respectively). The interactions of acetaminophen and anti-cholinergic agents comprised most types of drug–drug interactions (6.62%). ConclusionAlthough the prevalence rates of DDIs are low, life-threatening interactions may develop. Physicians must be reminded of the potential DDIs when prescribing medications for newborns and infants.

Drug–drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved

Mortality and morbidity are increased in patients experiencing drug-drug interactions (DDIs). Critically ill patients are at an increased risk of adverse events from DDIs due to the large number of medications that they take and their changes in organ function. Currently, there is a lack of literature describing DDIs in the intensive care unit (ICU). The purpose of this study is to evaluate frequency, severity and drug combinations involved in DDIs occurring in a medical ICU (MICU). This was a 4-week, prospective, observational study that was conducted in the MICU of an academic medical centre. Lexi-Interact and Micromedex interaction databases were utilized daily to screen patients' medication profiles for DDIs, and severity was assessed using each database's severity rating scale. Of 240 patient medication profiles evaluated, 457 DDIs were identified. The rate of DDIs was 190.4 DDIs/100 patient days with 297 of these interactions being unique drug pairs. About 25% (114/457) were considered major DDIs. The most commonly involved medications were antihypertensive medications (106/457) and anticoagulants/antiplatelet agents (80/457). DDIs occur frequently in the MICU. Severity and drug combinations related to DDIs in the MICU differ from DDIs published in other ICU settings. When developing a DDI alerting system, patient characteristics and location should be considered.

Assessment of drug-drug interactions among renal failure patients of nephrology ward in a south Indian tertiary care hospital

Polypharmacy is common in drug prescriptions of chronic kidney disease patients. A study of the prescription patterns of drugs with potential interactions would be of interest to prevent drug related adverse events. A prospective observational study of six months (Dec 2009-May 2010) was carried out among the chronic kidney disease patients admitted to the nephrology ward of a South Indian tertiary care hospital. The pattern and rates of drug-drug interactions seen in the prescriptions of these patients was studied. Among the 205 prescriptions included, a total of 474 interactions were reported, making 2.7 interactions per prescription with incidence rates of 76.09%. Around 19.62% of interactions were of major severity. Most common interactions were found between ascorbic acid and cyanocobalamine (12.45%), clonidine and metoprolol (3.80%) respectively. Hypo or hypertension (31.65%), decreased drug efficacy (29.11%) and hypo or hyperglycemia (14.14%), were the most commonly reported clinical outcomes of the drug interactions. Cardiovascular drugs (calcium channel blockers and beta blockers; 52%) constitute the major class of drugs involved in interactions. As most of the interactions had a delayed onset, long term follow-up is essential to predict the clinically significant outcomes of these interactions. Hence, drug interactions are commonly seen in the prescriptions of chronic kidney disease patients which can lead to serious adverse events if not detected early. Need for collaboration with a clinical pharmacist and electronic surveillance, which are absent in developing countries like India, is emphatic.

Statin Drug Interactions in Patients with Comorbidities and on Multiple Medications

Extensive clinical evidence has demonstrated the efficacy of statin treatment in the prevention of cardiovascular disease (CVD). However, nearly half of patients taking statins discontinue their use, largely as a result of side effects. Many patients receiving statins are elderly, and/or have comorbid conditions, increasing the potential for drug-drug interactions (DDIs). Statin DDIs are largely the result of altered drug metabolism via cytochrome P450s (CYPs), glucuronidation or altered drug transport via organic anion-transporting polypeptides (OATPs) and P-glycoprotein (P-gp). There is a need for discussion and education about DDIs within the clinical consultation. Statins that are not significantly metabolized via the CYP system have a reduced risk of DDIs. To date, pitavastatin has shown a low rate of DDIs compared to other available statins metabolized by CYP3A4 isozymes. Its potential for CYP-mediated DDIs has been studied in combination with a wide range of drug classes known to be CYP inhibitors and has been clinically evaluated in patients populations where multiple medications are used, including the elderly, those high risk of CVD, and those taking protease inhibitors. It may also have beneficial effects on parameters of glucose metabolism, and has shown improved outcomes in patients with chronic kidney disease. Knowledge of statin pharmacokinetics, their dose limitations and contraindications, and their mechanisms of DDI allows improved therapeutic choices, avoiding adverse interactions without compromising patient care.

Highly active antiretroviral therapy induced drug-drug interactions in Indian Human Immunodeficiency Virus positive patients

One of the greatest challenges for the HIV clinician is the recognition and management of drug interactions. The HIV infected patient often receives numerous medications and has a great potential for adverse drug interactions. Although many of these interactions may be minor in nature, some are potentially serious, leading to severe toxicity or treatment failure. The aim of this study is to determine the incidence, pattern and to identify risk factors for possible drug-drug interactions (DDIs) in human immunodeficiency virus positive patients with antiretrovirals (ARVs) in an Indian tertiary care teaching hospital. A prospective case control study was performed for monitoring drug-drug interactions to antiretroviral therapy during hospitalization from August 2009 to March 2010. Possible DDIs found were classified according to Tatro. The prescription of each enrolled patient during hospitalization was reviewed and analyzed by a graduate trainee clinical pharmacist for possible drug to drug interactions based on Online Stockley’s Drug Interactions (9th edition), Micromedex Online Drug Reference and Martindale, The Complete Drug Reference. The possible DDIs found were classified according to a clinical significance rating expressed as a number assigned to each DDI based on onset, severity and documentation. Multivariate logistic regressions were used to identify the risk factors for DDIs. The data consisted of 118 hospitalized HIV patients with ARV prescriptions. Out of which 175 DDIs were detected involving 77 patients. The overall incidence rate of DDIs was 65.2% and pharmacokinetic DDIs was the most commonly observed DDIs. ‘Minor’ and ‘moderate’ drug-drug interactions accounted for 50.8 and 26.9% respectively. A maximum of six DDIs was reported from a single patient. Most of the patients who developed DDIs were receiving more than nine to eleven drugs at the time of experiencing DDIs. Polypharmacy, tuberculosis and syphilis were observed as risk factors for DDIs. The increase in use of newer antiretrovirals in India increases the risk for drug interactions and complicates their management on HIV/AIDS. It is therefore recommended that clinicians must focus to detect potential DDIs at time of prescription of ARVs to ensure better patient care. Key words: Drug interactions, antiretroviral therapy, highly active, India.

Study of drug-drug interactions in prescriptions of general practitioners and specialists in iran 2007-2009.

Prescriptions written by general practitioners and medical specialists were studied and compared to determine the type, time of onset and clinical importance of drug-drug interactions (DDIs) in an attempt to reduce further complications. In 2007, 28, 956, 638 prescriptions and 15, 610, 912 prescriptions in 2008 were filled by pharmacies affiliated with medical science universities. These prescriptions, prescribed by physicians from 33 Iranian medical universities nationwide were then evaluated with a prescription processing software named Pardazesh Nosakh. After processing and analyzing the data, DDIs were discovered in 14 different medical specialists consisting of internists, cardiologists, neurologists, psychiatrists, neurosurgeons, general surgeons, infectious diseases, urologists, dermatologists, ENT, ophthalmologists, orthopedists, and pediatrician. The results were then analyzed through methods applied in the book of Drug Interaction Facts. The results revealed that in 2007-2008, 0.77% of prescriptions had DDIs out of which 0.67% were with significant clinical importance. The percentage of interactions with significant clinical importance was higher in prescriptions of medical specialists and of those, cardiologists and internists ranked top on the list, while dermatologists ranked the lowest. The most common interacting combination prescribed was digoxin and furosmide in 2007-2008, and captopril and triamteren in 2008-2009. Moreover, this study showed that polypharmacy was an important factor which led to DDIs. Drug interactions were common among outpatients prescribed multiple medications and the rate of DDIs increased with the number of drugs prescribed. It is our opinion that by being up-to-date on drug information and participating in related educational classes and workshops, physicians can increase the chances of choosing the correct drug treatment and hence significantly decrease possible DDIs side effects.

Potential drug–drug interactions in prescriptions dispensed in community pharmacies in Greece

To evaluate the nature, type and prevalence of potential drug-drug interactions (DDIs) in prescriptions dispensed in community pharmacies in Thessaloniki, Greece. Secondary objectives included the classification of DDIs as per pharmacotherapeutic class of the medications and the investigation of the relationship between medical specialties and the frequency of potential DDIs, as well as the relationship between DDIs and prescription size. Setting DDIs are a common cause of adverse drug reactions (ADRs) among patients using multiple drug therapy. In Greece a reliable computerized surveillance system for monitoring potential DDIs is not yet fully established. As a result, the prevalence of such DDIs in prescriptions dispensed by community pharmacies in Greece is unknown. We conducted a prospective, descriptive study. Over a 3-month period (November 2007-January 2008), a total of 1,553 handwritten prescriptions were collected from three community pharmacies in Thessaloniki, Greece. The prescriptions were processed using the Drug Interactions Checker within the www.drugs.com database. The identified potential DDIs were categorized into two classes, major and moderate, according to their level of clinical significance. Overall 213 prescriptions had one or more potential DDIs and a total of 287 major and moderate DDIs were identified. Potential DDIs were identified in 18.5% of all prescriptions. Major DDIs were identified in 1.9% of all prescriptions and represented 10.5% of all DDIs detected, whereas moderate DDIs were identified in 16.6% of all prescriptions and represented 89.5% of all DDIs detected. The rate of DDIs increased with prescription size. The most common drug involved in major DDIs was amiodarone which interacts with potassium-wasting diuretics, digoxin, simvastatin and acenocoumarol. Our results indicate that patients in Greece are at risk of ADRs caused by medications due to potential DDIs. An appropriate surveillance system for monitoring such interactions should be implemented and physicians should be more aware of potentially harmful DDIs. Pharmacists can contribute to the detection and prevention of drug-related injuries, especially of clinically meaningful DDIs that pose a potential risk to patient safety.