Potential Drug Interactions Research Articles

Monitoring the Levels of Antiepileptic Drugs for Therapeutic Purposes: an Overview of the Current Situation and Potential Future Advancements

Antiepileptic drugs (AEDs) play a crucial role in treating epilepsy, with expected variability in their pharmacokinetics across diverse patient groups such as children, the elderly, pregnant individuals, and those undergoing polytherapy with potential drug interactions. Additionally, ensuring patient adherence is essential. Therapeutic drug monitoring (TDM) serves as a valuable tool for maintaining treatment quality. Given the prevalence of pharmacokinetic variability among AEDs, TDM enables a personalized approach to epilepsy care by allowing adjustments based on individual drug concentrations. Currently, there are 27 licensed AEDs, making them one of the most common medications subject to TDM. This review aims to provide an overview of the existing evidence on the application of AED TDM in both epilepsy and non-epilepsy conditions. The extensive pharmacokinetic variability of AEDs results in significant variations in serum concentrations among patients, making TDM beneficial for tailoring treatment to individual needs. Indications for TDM encompass scenarios where optimization of clinical outcomes is crucial. Future advancements may involve incorporating additional markers of toxicity and genetic variability to further enhance individualization and optimize AED treatment.

A Review of CYP-Mediated Drug Interactions: Mechanisms and In Vitro Drug-Drug Interaction Assessment.

Drug metabolism is a major determinant of drug concentrations in the body. Drug-drug interactions (DDIs) caused by the co-administration of multiple drugs can lead to alteration in the exposure of the victim drug, raising safety or effectiveness concerns. Assessment of the DDI potential starts with in vitro experiments to determine kinetic parameters and identify risks associated with the use of comedication that can inform future clinical studies. The diverse range of experimental models and techniques has significantly contributed to the examination of potential DDIs. Cytochrome P450 (CYP) enzymes are responsible for the biotransformation of many drugs on the market, making them frequently implicated in drug metabolism and DDIs. Consequently, there has been a growing focus on the assessment of DDI risk for CYPs. This review article provides mechanistic insights underlying CYP inhibition/induction and an overview of the in vitro assessment of CYP-mediated DDIs.

Clinical pharmacy services in cancer patients with hypertension

Abstract Clinical pharmacy services aim to ensure the rational use of drugs and resolve disease/health conditions with a multidisciplinary approach. Pharmaceutical care plans need to be created to effectively provide clinical pharmacy services in the treatment of hypertension which is one of the common chronic diseases in cancer patients. In this mini-review, we examine which drugs can cause or worsen hypertension in patients receiving cancer treatment, potential drug-drug interactions between drugs used in cancer treatment and antihypertensive drugs, pharmacological and clinical studies for the treatment of hypertension in patients with hypertension before cancer diagnosis or newly diagnosed hypertension due to cancer treatment. Non-pharmacological treatment approaches are presented. We think that our study will be a resource that can be used to solve possible drug-related problems in the practice.

Pharmacokinetics of asundexian with combined CYP3A and P-gp inhibitors and an inducer: Target in vitro and in vivo studies.

Asundexian is an oral, direct and reversible inhibitor of activated factor XI (FXIa) in development for the treatment of thromboembolic events. This article summarizes results from preclinical and clinical studies, including identification of enzymes involved in asundexian pharmacokinetics, and evaluation of potential target drug-drug interactions. In vitro studies investigated the substrate characteristics of asundexian towards several cytochrome P450 (CYP) isoforms, hydrolytic enzymes and drug transporters. Inhibition of the amide hydrolysis of asundexian was investigated in vitro for several relevant drugs. Phase 1 studies in healthy male participants investigated the pharmacokinetics (PK) of asundexian upon co-administration of combined inhibitors or an inducer of P-gp and CYP3A4 (itraconazole, verapamil or carbamazepine, respectively, or the moderate CYP3A4 inhibitor fluconazole). The pharmacodynamic (PD) markers are activated partial thromboplastin time and FXIa inhibition. Asundexian was predominantly metabolized via carboxylesterase 1 and, to a lesser extent, via CYP3A4 and is a substrate of P-gp. The asundexian area under the plasma concentration-time curve (AUC) increased by 103% and 75.6% upon combined inhibition of P-gp and strong or moderate inhibition of CYP3A4, respectively, but was unaffected by moderate CYP3A4 inhibition. Combined P-gp and CYP3A4 induction by carbamazepine decreased asundexian AUC by 44.4%. PD is concentration-dependent, thus no differences in maximum responses and recovery commensurate with PK effect(s) were observed. Adverse events were mild and asundexian was well tolerated. The presented studies confirmed that CYP3A4 and P-gp contribute to asundexian metabolism and excretion. Observed effects were in line with data from a previous mass balance study.

Evaluation of Levofloxacin Prescription Pattern Based on International Standards in a Tertiary Hospital in Iran

Background: The emergence of antibiotic-resistant bacteria poses a significant global concern. The improper use of antibiotics, identified as a leading contributor to this problem, is a widespread issue in medical centers worldwide. Objectives: This study aimed to investigate the utilization pattern of levofloxacin, a commonly prescribed antibiotic. Methods: We conducted a retrospective descriptive study in Ahvaz, Iran, focusing on patients who had received levofloxacin over a 6-month period. Data collection involved a questionnaire comprising patient demographic details, diagnosis information, details concerning levofloxacin administration, and outcomes, all extracted from the patients' medical records. During the assessment, we considered factors such as the correct dosage, frequency of administration, potential drug interactions, and adverse effects. Data analysis was performed using SPSS v. 20. Results: A total of 35 patients, with a mean age of 55.17 ± 20.36 years, received levofloxacin during the study period, and 48.6% of them were women. On average, each patient received 3.20 ± 2.85 grams of levofloxacin, with a minimum dose of 0.500 grams and a maximum of 11.50 grams. The average treatment duration was 3.813 ± 4.26 days. In only 8.6% of cases, the prescribed dosage was deemed inappropriate, while in 40% of cases, the duration of antibiotic use was found to be inadequate. Conclusions: The utilization of levofloxacin was deemed irrational in 40% of cases. Although the prescribed dosage for the respective diagnoses was generally accurate, the treatment duration was often incorrect, potentially contributing to antibiotic resistance.

Predicting an Optimal Medication/Prescription Regimen for Patient Discordant Chronic Comorbidities Using Multi-Output Models

This paper focuses on addressing the complex healthcare needs of patients struggling with discordant chronic comorbidities (DCCs). Managing these patients within the current healthcare system often proves to be a challenging process, characterized by evolving treatment needs necessitating multiple medical appointments and coordination among different clinical specialists. This makes it difficult for both patients and healthcare providers to set and prioritize medications and understand potential drug interactions. The primary motivation of this research is the need to reduce medication conflict and optimize medication regimens for individuals with DCCs. To achieve this, we allowed patients to specify their health conditions and primary and major treatment concerns, for example, costs of medication, interactions with current drugs, and weight gain. Utilizing data gathered from MTurk and Qualtrics, we gained insights into healthcare providers’ strategies for making/customizing medication regimens. We constructed a dataset and subsequently deployed machine learning algorithms to predict optimal medication regimens for DCC patients with specific treatment concerns. Following the benchmarking different models, Random forest emerged as the top performer, achieving an accuracy of 0.93. This research contributes significantly to the enhancement of decision-making processes, empowers patients to take a more active role in their healthcare, and promotes more informed and productive discussions between patients and their care teams.

P13 Evaluation of in vitro activity of double β-lactam ‘therapy’ in ESBL+/CPE+ Escherichia coli—what is the association between ‘synergy’ and in vitro susceptibility?

Abstract Background With the increasing emergence of widespread antimicrobial resistance (AMR), finding therapeutic options for MDR organisms (MDRO), carbapenem-resistant Enterobacterales (CRE) and ESBL producers continues to represent a significant challenge. A promising therapeutic strategy against AMR is combination therapy, with the potential for synergistic drug interactions, reduced drug toxicity through reduced dosage drug–drug additive effects, repurposing of existing drugs, and the hope of overcoming resistance mechanisms and limiting resistance development. Methods We systematically determined the relationship between double β-lactam therapy (N=390 combinations) against five Escherichia coli strains of variable resistance in vitro (three clinical and two purchased isolates). This included ESBL producers (N=2) and carbapenemase producers (CPEs) (N=3). For each of 13 β-lactam antibiotics, the MIC was determined individually, and subsequently in combination, using the MTS™ ‘cross’ synergy method (Liofilchem, 2012). The FIC was calculated by dividing the MIC of each drug in combination by the MIC of each drug alone, and adding the results (Figure 1). Combinations were performed in duplicate, with a third combination performed if there was any discrepancy in result (∼18.7%). Individual and combination antibiotic results were next analysed according to EUCAST clinical breakpoints to determine if synergistic combinations correlated with a potentially improved in vitro susceptibility phenotype. A susceptibility phenotype improvement was defined: R/R or R/I or I/I monotherapy, improving to R/S, I/S or S/S combination therapy (where S=susceptible, I=intermediate and R=resistant). Results Overall, 64/390 (16.4%) combinations showed synergy; 106/390 (27.2%) were additive; 220/390 (56.4%) were indifferent. No antagonism was identified. Synergy was most commonly detected in ESBL producers (49/64;76.6% of synergistic combinations) and less frequently in CPEs (15/64; 23.4% combinations) (Figure 2). Of the synergistic combinations, 56/64 had ≥1 β-lactamase inhibitor present (87.5%). A total of 137/780 (17.6%) duplicate combinations showed improvement in EUCAST susceptibility between monotherapy and combination therapy (i.e. ≥1 R individually becoming ≥1 I or S in combination, or ≥1 I individually becoming ≥1 S in combination). But only 29/780 (3.7%) resulted in an R/R, R/I or I/I phenotype as monotherapy becoming ≥1 S in combination. Of the 137 duplicate combinations that improved, 55 (40.1%) were synergistic, 48 (35.1%) were additive and 34 (24.8%) were indifferent (by FIC index). Of 643/780 duplicate combinations that showed no improvement in susceptibility, 73 (11.35%) were synergistic, 164 (25.2%) were additive and 406 (63.45%) were indifferent. Of note, in 131/780 (16.8%) initial monotherapy susceptibility was S/S (i.e. further improvement not possible). Of these results, 33 (25.2%) were synergistic, 51 (38.9%) were additive and 47 (35.9%) were indifferent. Synergy was more common in combinations that improved by EUCAST susceptibility versus those that did not (χ2, P=0.00001). Ceftazidime/avibactam was the antibiotic most commonly present in synergistic combinations (27/64; 42.2%). Ceftazidime/avibactam/aztreonam was the combination most commonly associated with synergy (5/5 isolates) (Figure 3). Conclusions Synergy was most commonly detected in ESBL producers with most synergistic combinations containing one or two β-lactamase inhibitors. Synergy was less commonly seen in CPE producers. Overall, improvement in in vitro susceptibility by EUCAST criteria was infrequent, and is highly bug–drug–drug combination dependent, but there is a statistically significant association between EUCAST susceptibility improvement and synergistic combinations. Further work using alternative validating methodology and in more isolates is required.

Prevalence and factors associated with potential drug-drug interactions in prescriptions presented at private pharmacies in Mbarara city, southwestern Uganda.

Drug-drug interactions (DDIs) influence the effectiveness of medication and thus determine the treatment outcomes of diseases managed with pharmacotherapy. This study aimed to determine the prevalence, severity, and factors associated with potential drug-drug interactions in prescriptions presented at private pharmacies in Mbarara city. DDIs were identified and classified basing on risk and severity using Lexicomp drug interaction database. STATA version 13 was used to analyze the collected data. Descriptive statistics were used to summarize the severity of potential DDIs identified. Bivariate and multivariate logistic regression was employed to identify different factors associated with the presence of potential DDIs. A total of 295 prescriptions from 18 private pharmacies were studied and the prevalence of clinically significant potential DDIs was 37.6%. About half (149, 50.5%) of the patients were females, the majority (199, 67.5%) were adults 18-59 years of age whereas most (208, 70.5%) had a comorbid condition. Over one half (162, 54.9%) of the prescriptions were received from hospitals and majority of the prescriptions had 4 drugs prescribed (n= 175, 59.32%). Having one or more comorbidities and prescribing of therapeutic drug categories including anti-fungal, antihypertensives, analgesics, or corticosteroids were significantly associated with potential DDIs. The prevalence of potential drug-drug interactions in outpatient setting in Mbarara city was high and majority of the potential DDIs were of moderate severity. Having 1 or more comorbidities and prescribing of therapeutic drug categories including antifungals, antihypertensives, analgesics, or corticosteroids were significantly associated with potential DDIs.

Evaluation of potential drug-drug interactions of metformin using different software programs: A single-center retrospective study

Aim: Given that metformin is often recommended for the management of type 2 diabetes mellitus, it is clinically significant to consider the potential interactions between metformin and other medications. In this study, we aimed to identify potential drug-drug interactions associated with metformin by retrospectively analyzing the prescriptions of patients taking metformin. Materials and Methods: Metformin-containing prescription data of five independent community pharmacies in Konya province for the year 2023 were analyzed retrospectively. Medscape®, Drugs® and LexiComp® software programs were used to detect potential drug-drug interactions. As a result of power analysis with the G Power program, 400 patients were included in the study with an effect size of 0.25, type 1 error of 0.05 and confidence interval of 0.95. Kendall's W analysis was performed to determine the concordance between the software programs. Results: Kendall's W value indicating the agreement between Medscape®, Drugs® and LexiComp® software programs was calculated as 0.061. In terms of potential drug-drug interactions of metformin, the agreement between the software programs was observed to be slight. The highest agreement between the progrmas was observed between Medscape® and LexiComp® (Kappa coefficient=0.44). Conclusion: Since potential drug-drug interactions are common in prescriptions for patients taking metformin, these interactions should be carefully monitored. Clinicians should use multiple interaction programs to identify potential drug-drug interactions of metformin.

Potential drug-drug interactions between discharge medication from the emergency department and home medication in tertiary hospital

Objective: This retrospective analysis aimed to comprehensively examine the age distribution, gender prevalence, comorbidity patterns, and potential drug-drug interactions among discharged emergency department (ED) patients. By elucidating these factors, the study would contribute valuable insights for improving patient care and medication safety. Methods: The study used retrospective data collection and analyzed cross-sectional data of patients discharged from the ED at King Abdullah Medical City from January to February 2023. Results: The results showed that the majority of discharged patients were between the ages of 36 and 50 years (56.4%) and had a balanced gender distribution. The most common department of discharge was cardiology (42.1%). The analysis also revealed that 68.5% of patients had 3 to 6 comorbidities. The study found significant associations between discharge status and potential drug-drug interactions (DDIs), with patients discharged against medical advice having a higher incidence of potential DDIs (p = 0.037). Conclusion: The study highlighted the importance of training emergency physicians to use hospital systems to identify and prevent potential DDIs. The prevalence of DDIs between prescribed ED medication and home medication was found to be high. The study suggested that discharge status and DDI severity are significant factors influencing the frequency of potential DDIs.

Cardiovascular Drug Interactions with Nirmatrelvir/Ritonavir for COVID-19: Considerations for Daily Practice.

Cardiovascular disease is associated with progression to severe COVID-19 and patients with the condition are among those in whom early antiviral therapy should be warranted. The combination of nirmatrelvir/ritonavir (Paxlovid®) has been approved for clinical use by the Food and Drug Administration and European Medicines Agency. Because patients with cardiovascular disease are often on polypharmacy, physicians need to be aware of potential drug-drug interactions (DDIs) when treating COVID-19 with nirmatrelvir/ritonavir. Guidance is given for avoiding DDIs, emphasising that preventing and managing potential DDIs with nirmatrelvir/ritonavir requires thorough assessment and knowledge. The present review summarises the clinical pharmacology of nirmatrelvir/ritonavir and provides details on potential DDIs with a focus on daily practice in patients with cardiovascular disease. Particular attention is needed for drugs that are predominantly metabolised by cytochrome P450 3A4, are substrates of P-glycoprotein and have a narrow therapeutic index. Proper management of potential DDIs must balance the benefit of nirmatrelvir/ ritonavir to prevent severe disease with the risk of serious adverse events.

Drug safety in older patients with alcohol use disorder: a retrospective cohort study.

Older patients with alcohol use disorder are at particular risk of developing adverse drug reactions due to multimorbidity, polypharmacy, and altered organ function. In this study, we investigated the frequency and characteristics of potentially serious alcohol-medication interactions, potentially inappropriate medications (PIMs) for older adults, and potential drug-drug interactions (pDDIs) in a population of older patients with alcohol use disorder over a 10-year period. Retrospective monocentric cohort study. Prescribed medications were screened for potentially serious alcohol-medication interactions, PIMs, and pDDIs using the POSAMINO (POtentially Serious Alcohol-Medication INteractions in Older adults) criteria, the PRISCUS 2.0 list, the FORTA (Fit fOR The Aged) classification, and the drug interaction program AiDKlinik®. We enrolled 114 patients aged ⩾65 years with alcohol use disorder, who were treated in an addiction unit of a university hospital in Germany. About 80.7% of the study population had at least one potentially serious alcohol-medication interaction. Potentially serious alcohol-medication interactions most commonly affected the cardiovascular (57.7%) and the central nervous system (32.3%). A total of 71.1% of the study population received at least one prescription of a FORTA C or D drug, compared with 42.1% who received at least one PIM prescription according to the PRISCUS 2.0 list. A total of 113 moderate and 72 severe pDDIs were identified in the study population. Older patients with alcohol use disorders are frequently exposed to potentially serious alcohol-medication interactions, PIMs, and pDDIs. Improvements in the quality of prescribing should primarily target the use of cardiovascular and psychotropic drugs.

Potential Drug-Drug Interactions among Geriatric Patients in Medicine Department at a Tertiary Care Teaching Hospital - A Prospective Observational Study

Background Drug-drug interactions occur when therapeutic effect of one drug is altered by another drug during co-administration. These effects may result in increase or decrease in the action of either of the substances or it may cause adverse effect that is abnormally associated with either of the drugs. Data was collected from patients admitted in the Emergency Department.Aim The objective of the study was to identify evaluate and analyze the drug-drug interactions found in the prescriptions of elderly patients visiting the Medical department at a tertiary care teaching hospital.Methods This prospective observational study was undertaken in an Emergency ward for a period of six months to identify evaluate and analyze the drug-drug interactions. Ethical clearance was obtained from the Institutional Ethical Committee of SCS College of Pharmacy Harapanahalli. A total of three hundred and fifty cases were reviewed and details such as demographics past medical and medication history prescribed drugs and drug interactions were recorded.Results The data of 350 patients was included in the study. In our study a total of 405 drug-drug interactions were seen in 191 patients. The most commonly involved drugs were hydrocortisone and furosemide. Increased polypharmacy was observed in patients with co-morbid conditions leading to increased risk of potential drug-drug interactions PDDI.Conclusion Our study revealed that geriatric patients have higher risk for polypharmacy due to the presence of co-morbid conditions. Overall the incidence of PDDI was high and most interactions were pharmacodynamic in nature.nbsp

Mechanism of Qiguiyin Decoction Sensitizing Levofloxacin Against Multidrug-Resistant Pseudomonas aeruginosa Infection Based on PK-PD and Antibody Chip Technology.

Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection. Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD. QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group. These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.

A cross-sectional study to determine the potential drug–drug interactions in patients with alcoholic liver disease in a tertiary care hospital

Background: Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide, and it significantly contributes to liver-related mortality on a global scale. These patients often require drug treatment either for liver disease and its complications or for other comorbid conditions. Due to compromised hepatic function and the prevalence of polypharmacy-associated comorbidities, liver disease significantly increases the risk of drug-drug interactions (DDIs) and adverse drug reactions (ADRs). Aims and Objectives: The aim of the study was to determine the potential drug interactions in the pharmacological management of patients with alcoholic liver disease undergoing conservative treatment. Materials and Methods: A descriptive and cross-sectional study was conducted at Victoria Hospital attached to Bangalore Medical College and Research Institute over a period of 3 months. The study analyzed 200 cases of alcoholic liver disease for the presence of potential drug interactions using the LEXICOMP computer program. Results: The study included 200 subjects with alcoholic liver disease. About 92% were males, and 35% were from the age group of 41 to 50 years followed by 28% from 31 to 40 years. Cirrhosis was identified in 53% of the cases. The median number of drugs per patient was 8.8. A total of 118 potential DDIs (pDDIs) were identified averaging 2.5 pDDIs per patient. The common pDDIs were seen with ondansetron, metronidazole, propranolol, rifaximin, and ranitidine. It was noted that polypharmacy exhibited a robust association with the occurrence of drug interactions. The findings highlight a significant association between polypharmacy and the incidence of pDDIs. Conclusion: The complexity of pharmacotherapy in alcoholic liver disease stems from compromised liver function. It is crucial for physicians to be cognizant of the significant DDIs associated with medications used in liver disease treatment, given the heightened susceptibility of these patients to ADRs.

Should Cannabis be Used for Anorexia in Patients With Cancer?

Healthcare professionals are frequently asked about the benefits of cannabis for appetite or anorexia-cachexia syndrome. In popular culture, cannabis has a reputation of causing an increased hunger, slang termed “the munchies,” so many patients consume this with the hope that it may improve the loss of appetite associated with serious illness such as cancer. There have only been a few randomized, controlled trials studying the controversial question as to if cannabis improves appetite. These studies are small and show no statistically significant benefit for appetite and one small study showed improvement of taste for foods. Due to regulation barriers, the studies have use synthetic products, not the products that represent what is more commonly used in the population, often whole flower smoked, vaporized or oral products. Despite the popularity of cannabis in culture, often touted as a panacea for all maladies, the evidence and education for several adverse effects and potential drug interactions have has yet to catch up with the cultural craze. International cannabis experts in the United States and Australia do not routinely certify patients for medical cannabis off trial for anorexia-cachexia, but one expert in Canada would consider use in selected cancer patients.

Potentially inappropriate medications with older people in intensive care and associated factors: a historic cohort study.

The epidemiology of potentially inappropriate medications (PIMs) in critical care units remains limited, especially in terms of the factors associated with their use. To estimate the incidence and factors associated with PIMs use in intensive care units. Historical cohort study was conducted in a high-complexity hospital in Brazil. A retrospective chart review was conducted on 314 patients aged ≥ 60 years who were admitted to intensive care units (ICUs) at a high-complexity hospital in Brazil. The dates were extracted from a "Patient Safety Project" database. A Chi-square test, Student's t-test, and multivariable logistic regression analyses were performed to assess which factors were associated with PIMs. The statistical significance was set at 5%. According to Beers' criteria, 12.8% of the identified drugs were considered inappropriate for the elderly population. The incidence rate of PIMs use was 45.8%. The most frequently used PIMs were metoclopramide, insulin, antipsychotics, non-steroidal anti-inflammatory drugs, and benzodiazepines. Factors associated with PIMs use were the number of medications (odds ratio [OR] = 1.17), length of hospital stay (OR = 1.07), and excessive potential drug interactions (OR = 2.43). Approximately half of the older adults in ICUs received PIM. Patients taking PIMs had a longer length of stay in the ICU, higher numbers of medications, and higher numbers of potential drug interactions. In ICUs, the use of explicit methods combined with clinical judgment can contribute to the safety and quality of medication prescriptions.

The effect of computerised decision support alerts tailored to intensive care on the administration of high-risk drug combinations, and their monitoring: a cluster randomised stepped-wedge trial

Drug-drug interactions (DDIs) can harm patients admitted to the intensive care unit (ICU). Yet, clinical decision support systems (CDSSs) aimed at helping physicians prevent DDIs are plagued by low-yield alerts, causing alert fatigue and compromising patient safety. The aim of this multicentre study was to evaluate the effect of tailoring potential DDI alerts to the ICU setting on the frequency of administered high-risk drug combinations. We implemented a cluster randomised stepped-wedge trial in nine ICUs in the Netherlands. Five ICUs already used potential DDI alerts. Patients aged 18 years or older admitted to the ICU with at least two drugs administered were included. Our intervention was an adapted CDSS, only providing alerts for potential DDIs considered as high risk. The intervention was delivered at the ICU level and targeted physicians. We hypothesised that showing only relevant alerts would improve CDSS effectiveness and lead to a decreased number of administered high-risk drug combinations. The order in which the intervention was implemented in the ICUs was randomised by an independent researcher. The primary outcome was the number of administered high-risk drug combinations per 1000 drug administrations per patient and was assessed in all included patients. This trial was registered in the Netherlands Trial Register (identifier NL6762) on Nov 26, 2018, and is now closed. In total, 10 423 patients admitted to the ICU between Sept 1, 2018, and Sept 1, 2019, were assessed and 9887 patients were included. The mean number of administered high-risk drug combinations per 1000 drug administrations per patient was 26·2 (SD 53·4) in the intervention group (n=5534), compared with 35·6 (65·0) in the control group (n=4353). Tailoring potential DDI alerts to the ICU led to a 12% decrease (95% CI 5-18%; p=0·0008) in the number of administered high-risk drug combinations per 1000 drug administrations per patient, after adjusting for clustering and prognostic factors. This cluster randomised stepped-wedge trial showed that tailoring potential DDI alerts to the ICU setting significantly reduced the number of administered high-risk drug combinations. Our list of high-risk drug combinations can be used in other ICUs, and our strategy of tailoring alerts based on clinical relevance could be applied to other clinical settings. ZonMw.

Therapeutic strategies during cenobamate treatment initiation: Delphi panel recommendations.

The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically on ⩾2 ASMs, increasing the potential for drug-drug interactions. Early emerging AEs may impact adherence, decrease quality of life, and delay achieving optimal treatment dosages. Cenobamate is an oral ASM with a long half-life which has proven to be highly effective in clinical trials. An international Delphi panel of expert epileptologists experienced in the clinical use of cenobamate and other ASMs was convened to develop consensus best practices for managing patients during and after cenobamate titration, with consideration for its known pharmacokinetic and pharmacodynamic interactions, to allow patients to reach the most appropriate cenobamate dose while limiting tolerability issues. The modified Delphi process included one open-ended questionnaire and one virtual face-to-face meeting. Participants agreed that cenobamate can be prescribed for most patients experiencing focal-onset seizures. Patients initiating cenobamate therapy should have access to healthcare professionals as needed and their treatment response should be evaluated at the 100-mg dose. Patients with intellectual disabilities may need additional support to navigate the titration period. Proactive down-titration or withdrawal of sodium channel blockers (SCBs) is recommended when concomitant ASM regimens include ⩾2 SCBs. When applicable, maintaining a concomitant clobazam dose at ~5-10 mg may be beneficial. Patients taking oral contraceptives, newer oral anticoagulants, or HIV antiretroviral medications should be monitored for potential interactions. Because clinical evidence informing treatment decisions is limited, guidance regarding dose adjustments of non-ASM drugs was not developed beyond specific recommendations presented in the Summary of Product Characteristics.

Polifarmacija i rizik od lek-lek interakcija kod bolesnika sa reumatoidnim artritisom

Introduction/Aim. Polypharmacy can increase the risk of side effects and cause adverse drug interactions with a significant impact on the course of the basic disease. The aim of the study was to determine the frequency of polypharmacy and examine its impact on the risk of drug-drug interactions in patients with rheumatoid arthritis (RA). The research was conducted in the form of a retrospective cross-sectional study. Material and methods. The study included 131 patients diagnosed with RA, treated during 2019 and 2020. Demographic data and clinical characteristics of the subjects were collected from the medical documentation (presence of comorbidities, prescribed therapy and number of drugs). In the study, polypharmacy was defined as the use of more than five drugs, regardless of the length of therapy. Results. The data analysis of the therapy used by patients showed that 84 subjects (64.12%) used 5 - 9 drugs, both for the treatment of primary and for the treatment of other present acute and chronic diseases. The analysis of the collected results identified potential interactions in 86 respondents (65.65%), while the total number of potential interactions was 164. The most common potential interactions were serious (73.78%). Analyzing the obtained results, it appears that aceclofenac is the drug that has the potential to enter into the largest number of interactions with the drugs used in the therapy of RA. Conclusion. Given the wide range of available drugs and therapeutic modalities used in the treatment of RA, it is necessary to choose the right combination of drugs in order to achieve the desired therapeutic outcomes and minimize potential drug-drug interactions.