Management Of Drug Interactions Research Articles

Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants: an intervention study in community pharmacies

IntroductionDirect oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. MethodsWe conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. ResultsIn total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. ConclusionsThis study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations.

Enzalutamide: Understanding and Managing Drug Interactions to Improve Patient Safety and Drug Efficacy.

Enzalutamide is an oral androgen receptor signaling inhibitor utilized in the treatment of men with prostate cancer. It is a moderate inducer of the cytochrome P450 (CYP) enzymes CYP2C9 and CYP2C19, and a strong inducer of CYP3A4. It was also shown to be a mild inhibitor of the efflux transporter P-glycoprotein in patients with prostate cancer. Enzalutamide is primarily metabolized by CYP3A4 and CYP2C8. The risk of enzalutamide drug interactions arises primarily when it is coadministered with other drugs that interact with these CYPs, including CYP3A4. In this review, we begin by providing an overview of enzalutamide including its dosing, use in special populations, pharmacokinetics, changes to its prescribing information, and potential for interaction with coadministered drugs. Enzalutamide interactions with drugs from a wide range of medication classes commonly prescribed to patients with prostate cancer are described, including oral androgen deprivation therapy, agents used to treat a range of cardiovascular diseases, antidiabetic drugs, antidepressants, anti-seizure medications, common urology medications, analgesics, proton pump inhibitors, immunosuppressants, and antigout drugs. Enzalutamide interactions with common vitamins and supplements are also briefly discussed. This review provides a resource for healthcare practitioners and patients that will help provide a basis for the understanding and management of enzalutamide drug-drug interactions to inform decision making, improve patient safety, and optimize drug efficacy.

Drug-drug interactions with oral anticoagulants: information consistency assessment of three commonly used online drug interactions databases in Switzerland.

Background: Toxicity or treatment failure related to drug-drug interactions (DDIs) are known to significantly affect morbidity and hospitalization rates. Despite the availability of numerous databases for DDIs identification and management, their information often differs. Oral anticoagulants are deemed at risk of DDIs and a leading cause of adverse drug events, most of which being preventable. Although many databases include DDIs involving anticoagulants, none are specialized in them. Aim and method: This study aims to compare the DDIs information content of four direct oral anticoagulants and two vitamin K antagonists in three major DDI databases used in Switzerland: Lexi-Interact, Pharmavista, and MediQ. It evaluates the consistency of DDIs information in terms of differences in severity rating systems, mechanism of interaction, extraction and documentation processes and transparency. Results: This study revealed 2'496 DDIs for the six anticoagulants, with discrepant risk classifications. Only 13.2% of DDIs were common to all three databases. Overall concordance in risk classification (high, moderate, and low risk) was slight (Fleiss' kappa = 0.131), while high-risk DDIs demonstrated a fair agreement (Fleiss' kappa = 0.398). The nature and the mechanism of the DDIs were more consistent across databases. Qualitative assessments highlighted differences in the documentation process and transparency, and similarities for availability of risk classification and references. Discussion: This study highlights the discrepancies between three commonly used DDI databases and the inconsistency in how terminology is standardised and incorporated when classifying these DDIs. It also highlights the need for the creation of specialised tools for anticoagulant-related interactions.

Management of direct oral anticoagulant drug interactions in hospitalized patients.

Moderate-strong CYP3A4 or Pgp inhibitors and inducers alter direct oral anticoagulant (DOAC) pharmacokinetics. Whether the presence of a DOAC drug-drug interaction (DDI) prompts in- hospital changes in management remains unknown. We identified all hospitalized patients at our institution who were admitted with a clinically relevant DOAC DDI from 01/2021 to 06/2021. Clinically relevant DOAC DDIs were defined as those listed in the prescribing information or FDA CYP3A4/Pgp inhibitors clinical indexes. We assessed the prevalence of DOAC DDIs and categorized their management as: drug stopped, drug held, or drug continued. For drugs that were continued we assessed whether the dose of the DOAC or interacting drug was increased, decreased or unchanged during the admission. We ascertained the number of DOAC DDIs that prompted an automated prescribing alert in our electronic health record (EHR). Finally, we conducted a logistic regression model to compare users of DOACs with DDI who had their regimen adjusted versus those without adjustments, focusing on outcomes of rehospitalization and death, adjusting for age and gender. Among 3,725 hospitalizations with a DOAC admission order, 197 (5%) had a clinically relevant DOAC DDI. The DOAC and the interacting drug were continued at discharge for 124 (63%) hospitalizations. The most frequent adjustments were stopping the interacting drug (73%) and stopping the DOAC (15%). Only 7 (4%) of DOAC DDIs prompted an EHR alert. The adjusted odds ratios for rehospitalizations and death, respectively, among patients whose regimens were adjusted compared to those whose were not, were 1.29 (95% CI, 0.67 to 2.48; P = 0.44) and 1.88 (95% CI, 0.91 to 3.89; P = 0.09). Clinically relevant DDIs with DOACs occur infrequently among hospitalized patients and usually are managed without stopping the DOAC. The clinical impact of such DDIs and subsequent adjustments on thrombotic and hemorrhagic outcomes requires further investigation.

Pharmacist's role in the management of drug-drug interactions caused by nirmatrelvir/ritonavir in COVID-19 oncohematology patients.

New drugs developed for SARS-CoV-2 infection, such as nirmatrelvir/ritonavir (NMV/r), represent a potential for oncohematology patients, but also pose a challenge in managing the potential clinically relevant drug-drug interactions (pDDIs) that may arise. The aim of this study is to assess the frequency, severity, and pharmacist detection of pDDIs. This prospective, observational, study spanned 8 months, involving 42 oncohematology patients prescribed NMV/r in a tertiary-level hospital. A Board Certified oncology pharmacist assessed pDDIs using three databases and made recommendations to prescribing physicians. Linear and logistic regression analyses were employed to explore the relationship between prescribed drugs and pDDIs. Clinically relevant pDDIs were detected in 76.2% of patients, with 18.1% of all medications involved in drug-drug interactions (DDIs). The most common drugs implicated were atorvastatin and imatinib. Micromedex® identified 63.3% of interactions as major severity, while Lexicomp® and University of Liverpool classifications were less restrictive. Pharmacists prevented most DDIs from reaching patients through different interventions, including treatment monitoring (44.2%), discontinuation (36.5%), and dose reduction (17.3%). This study highlights the high prevalence of clinically significant pDDIs in oncohematology patients receiving NMV/r for COVID-19. Pharmacists, as integral members of the healthcare team, played a crucial role in detecting, categorizing, and mitigating these interactions. The results underscore the need for comprehensive studies to evaluate the impact of pharmacist-led interventions in optimizing drug therapy and enhancing patient safety in this vulnerable population.

FARMACOVID: Longitudinal Study of the Profile and Management of Drug Interactions in Critically Ill Patients with COVID-19

Background: Critically ill patients with COVID-19 have important risk factors for drug– drug interactions. Objective: This study aimed to characterize and describe the profile and management of drug–drug interactions in critically ill patients affected by COVID-19 in a tertiary care hospital in Colombia. Methods: A descriptive retrospective cohort with an exploratory analytical component was used. The medical records of 191 patients were reviewed from August 2020 to February 2021. An initial descriptive analysis was performed, and a bivariate analysis was developed to include variables of significance in a multivariate analysis. Results: In our cohort of critically ill patients, the following factors were associated with a higher risk of major outcome development: a higher age (p = 0.037), Charlson comorbidity index (CCI) (p = 0.001), Sequential Organ Failure Assessment (SOFA) score (p = 0.001), a greater number of prescribed drugs, number of interactions, and the presence of type-D interactions. Conclusion: Identifying clinical predictors and types of drug interactions may alter the development of major outcomes such as mortality.

Evaluation of the drug-drug interaction between triazole antifungals and cystic fibrosis transmembrane conductance regulator modulators in a real-life cohort.

Limited data on the clinical management of drug-drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population.

Impact of a clinical pharmacist‐led COVID‐19 treatment consult service in two primary care seniors clinics

AbstractIntroductionHealthcare utilization due to COVID‐19 infection is more prevalent in the older adult population. Nirmatrelvir/ritonavir is an oral antiviral option that can decrease the hospitalizations in older adults but has many of drug–drug interactions that need evaluation.ObjectivesThe objective of this study was to evaluate the impact of a clinical pharmacist COVID‐19 treatment consult service.MethodsClinical pharmacists were consulted to assess and provide COVID‐19 therapy recommendations for adults 65 years and older who tested positive for COVID‐19 in two primary care clinics. Recommendations for the most appropriate COVID‐19 therapy were sent to the primary care provider for review and discussed with the patient. Healthcare utilization, reinfection with COVID‐19, and safety of COVID‐19 therapies were evaluated.ResultsOne hundred and twenty four patients, average age of 82 years, received clinical pharmacy assessment for COVID‐19 therapy. Pharmacists recommended treatment with nirmatrelvir/ritonavir in 80% of patients. Medication modifications due to drug–drug interactions were required in 88% of patients receiving nirmatrelvir/ritonavir. Thirteen patients were recommended or opted to receive alternative COVID‐19 treatment while 36 patients declined COVID‐19 treatment, despite provider and pharmacist recommendations. Nineteen patients had an emergency department visit or hospitalization related to COVID‐19 within 30 days of pharmacy consult; 15 of the patients had been treated with COVID‐19 therapy and 4 declined therapy (p = 0.58). Eight patients experienced reinfection with COVID‐19. Only one patient reported an adverse event of hives within 30 days of receiving nirmatrelvir/ritonavir therapy.ConclusionA pharmacist‐led consult service for evaluating and recommending COVID‐19 antiviral therapies resulted in successful triage, while balancing management of drug interactions in a high‐risk patient population. No significant difference was found in healthcare utilization or reinfection between patients who received a COVID‐19 therapy and those who did not.

42P Development of an online tool for the management of drug-drug interactions with the ROS1/TRK tyrosine kinase inhibitor repotrectinib

42P Development of an online tool for the management of drug-drug interactions with the ROS1/TRK tyrosine kinase inhibitor repotrectinib

Assessment of potential drug-drug interactions in hospitalized cancer patients.

Drug-drug interactions (DDIs) pose a significant threat to patients with cancer, resulting in several adverse events in an oncology setting. Our study aims to identify potential DDIs in inpatient oncology wards, assess their severity, and provide recommendations to avoid these interactions. This prospective study was conducted in 79 hospitalized cancer patients over a period of 9 months (from August 2021 to May 2022) at the Amrita Institute of Medical Sciences, Kochi receiving at least two oncological or non-oncological drugs for 5 days. Significant differences were found in drug count (61.6% vs. 38.4%), hospitalization duration (63.1% vs. 36.9%), and medications for comorbidities (63% vs. 37%) between patients with and without DDIs (p < 0.001, <0.001, and 0.01, respectively). The study identified 321 DDIs, with 14 (4.4%) X interactions, 93 (30%) D interactions, 161 (50%) C interactions, and 53 (15.6%) B interactions. Severity-wise, 76 (23.7%) were major, 190 (59.1%) were moderate, and 55 (17.2%) were minor. Our study showed that drug count, medications for comorbidities, and hospitalization duration significantly increase the risk of DDIs in hospitalized oncology patients. Around 96.4% of recommendations for potential interactions were accepted and implemented, highlighting the huge opportunities and requirements for improvement, implementation, and management of drug interactions in oncology settings.

Cognitive task analysis of clinicians’ drug–drug interaction management during patient care and implications for alert design

BackgroundDrug–drug interactions (DDIs) are common and can result in patient harm. Electronic health records warn clinicians about DDIs via alerts, but the clinical decision support they provide is inadequate. Little...

Establishment of a Clinical Pharmacist-Led Multiple Myeloma Clinic with Collaborative Prescribing Model at the National Center for Cancer Care and Research in Qatar

Introduction Multiple Myeloma (MM) is a chronic and incurable hematologic malignancy affecting the plasma cells, and is more prevalent among the elderly. Interprofessional patient care showed superiority over physician-only care in multiple settings, including MM. (Sweiss K et al.2019)In Qatar, real-world data analysis of MM patients treated in the ambulatory setting at the National Center for Cancer Care and Research (NCCCR) showed that clinical pharmacists (CPs) had an evident role in therapy optimization and ensuring adherence to treatment protocol schedule and supportive medications.(Elazzazy S et al.,2023) We aimed to provide a more structured and accessible link to MM patients considering the complexity of their treatment protocols and supportive care through the establishment of a clinical pharmacist-led clinic (CPLC). The most common challenges to optimum care of MM patients in the NCCCR before CPLC were identified and categorized (Figure 1) and then used to design the collaborative model for the MM CPLC (Figure 2). Methods The collaborative MM CPLC was initiated at NCCCR in February 2022. A collaborative practice agreement was established for this clinic, to allow clinical pharmacists -managing MM patients- to issue refills for supportive medications, and order any necessary laboratory tests. To investigate the quality of care provided by the clinic, data was retrospectively collected and analyzed for all MM patients managed in the clinic between February 2022 and February 2023. All patients who were newly diagnosed with MM were eligible for referral by the attending physician. Dedicated advanced hematology CPs provided consultation twice weekly for referred patients without additional fees. The provided services (in-person or virtual) included thorough medication profile review (prescribed antineoplastic and refills of supportive medications), and ordering follow-up laboratory tests. Services also included assessment and optimization of medication adherence, including immunomodulators and supportive medications (i.e., Venous Thromboembolism (VTE) prophylaxis, antimicrobial prophylaxis, bone modifying agents and vaccinations), providing comprehensive patient education, and communicating the recommended adjustments with physicians. Results During the 12-month period, there was a total of 22 patients referred to the clinic. The average age for patients was 51 years (range 36-72). Patient characteristics are summarized in Table 1. The total number of documented encounters with the pharmacists was 73 visits, corresponding to a median of 4 visits per patient (range 1-11). The total amount of time spent with each patient over the course of their referral was 15 minutes. A total of 343 CPs interventions (average of 5 interventions per visit) were performed with an acceptance rate of 100%. The most common intervention was medication reconciliation (n=124), followed by monitoring for medication outcomes (n=72, safety and efficacy), addition of required medication (n=40), patient education (n=27), issuing refills (n=24), drug interactions review and management (n=19), suggesting referrals to relevant subspecialities (n=16), identification of adverse drug reactions (n=7), and required dose adjustments (n=12). Twenty-two medication refills for supportive medications and eight pre-chemotherapy laboratory investigations were issued and ordered by CPs, respectively. All newly diagnosed patients were started on the appropriate bisphosphonate therapy without the previously observed delay, with the median from diagnosis to initiation being 14 days [range from 1 to 117 days]. All clinic patients were maintained on the appropriate VTE prophylaxis (aspirin [n=14], rivaroxaban [n=7], warfarin [n=1]). All patients were adherent to antiviral and Pneumocystis jirovecii Pneumonia prophylaxis. Conclusion CPLC for MM patients treated in the ambulatory setting provided a robust and timely link to patients in alignment with the published literature. The newly implemented collaborative prescribing model in MM clinic encouraged the expansion of pharmacy services in other ambulatory clinics. Our collaborative model could be potentially applied to different cancer settings to optimize a safe and effective patient care. Further analysis is planned to compare the adherence to international MM care guidelines pre- and post-launch of our CPLC.

928. Concordance with Institutional Guidelines for Letermovir Cytomegalovirus Infection Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Abstract Background Cytomegalovirus (CMV) is an opportunistic infection in immunocompromised patients associated with significant morbidity and mortality. Letermovir (LET) is used for prophylaxis for CMV-seropositive allogeneic hematopoietic stem cell transplant (HSCT) recipients. An institutional guideline was developed to provide guidance on the appropriate use of letermovir. The purpose of this study was to determine overall concordance with letermovir institutional guidelines and to identify areas for quality improvement. Methods Our evaluation included adult hospitalized patients admitted from November 2019 to July 2022 for allogeneic HSCT who received LET, identified via medication administration records. The primary outcome was concordance with the institutional guideline criteria for use, as outlined in Figure 1. Secondary outcomes included incidence of breakthrough CMV viremia, use of concomitant HSV prophylaxis, and appropriate management of drug interactions (Figure 1). Results We identified 41 patients who received LET during the study period. After excluding patients who received a solid organ transplant, 32 patients were included in the study. The median time to LET initiation post-transplant was 7 days and the median time to discontinuation was 105 days post-transplant. Overall, 9 patients (28%) were fully concordant with our guidelines. Of the remaining patients, reasons for discordance are summarized in Table 1, mainly driven by continuation of LET &amp;gt;110 days post-transplant (n=12, 37%). Three (9%) patients received LET despite CMV recipient negative serostatus (CMV R-). Breakthrough CMV viremia occurred in 3 patients (9%). All patients received concomitant HSV prophylaxis and had drug interactions managed appropriately. Conclusion Our evaluation identified a lower than expected rate of letermovir guideline concordance, primarily related to the recommended duration of drug therapy. We found that our guideline has supported providers to ensure that concomitant HSV prophylaxis is given and drug interactions are managed appropriately. A further investigation into the use of letermovir in CMV R- subjects and a cost analysis is planned to guide future institutional guideline updates. Disclosures Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support

Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants in ambulatory care: a prospective interventional study in community pharmacies

Abstract Background/Introduction Direct oral anticoagulants (DOACs) are increasingly used but can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Community pharmacists, who have access to patients’ complete medication profiles, including over-the-counter medication and medication from different prescribers, can play a crucial role in detecting and managing DDIs with DOAC in ambulatory care. Purpose This study aimed to detect and manage DDIs with DOAC in ambulatory care, because such real-life clinical practice studies are currently lacking. Methods A prospective interventional study was conducted between October 2021 and August 2022 in 201 community pharmacies in Belgium. On random days, every patient purchasing a DOAC or an interacting drug was screened for the presence of a DDI with DOAC. The pharmacist contacted the physician to discuss the management of the interaction. For the screening and management of DDI with DOAC, a previously developed practice-oriented DDI list for ambulatory care was used [1]. Results In total, 751 patients (74.5±10.7 years) were included, in whom 875 DDIs were identified. The three most commonly involved interacting drugs were (selective) serotonin (norepinephrine) reuptake inhibitors (32.9%), antiplatelets (30.9%), and non-steroidal anti-inflammatory drugs (28.9%). Most DDIs (83.1%) were not new (patients were already using these drugs) and 8.7% of interacting drugs were dispensed over-the-counter. In almost one-third of DDIs (28.0%), the interacting drug and the DOAC were prescribed by different physicians. Prescribers rated the clinical risks of the identified DDIs as high (15.9%), moderate (33.1%), and low (38.7%), whereas 12.3% were unaware of the potential risks. Remarkably, in 18 patients who were concomitantly taking an antiplatelet and DOAC, the prescriber reported forgetting to stop the antiplatelet or not being aware that the patient was taking both medications. Three patients were also found to be using another anticoagulant along with DOAC due to miscommunication between prescribers. When discussing how to manage the DDI, pharmacotherapy was mostly unchanged (60.2%). Physicians cited reasons such as the interacting drug being deemed necessary (37.2%), the patient already using a proton pump inhibitor (PPI) (19.5%), or the patient using both interacting drugs already for a long time without problems (18.6%). However, in 39.8% of cases, the discussion resulted in a pharmacotherapy change. The most common changes included stopping the interacting drug (21.5%), initiating a PPI (17.6%), or replacing the interacting drug with a safer alternative (14.5%). Conclusion This study illustrated that community pharmacists, in collaboration with physicians, can contribute to reducing avoidable patient harm from DDIs with DOACs.

Annual cost and implementation of remote oncology pharmacist order review within a network of community oncology practices.

30 Background: The US Oncology Network’s ClinReview program employs a team of centralized clinical pharmacists providing remote services to community oncology practices. Literature demonstrating the clinical impact of the oncology pharmacist has been well established. However, comprehensive data supporting the financial value compensating these clinical services continues to prove challenging. The aim of this study is to evaluate the annual cost-avoidance realized by the ClinReview program through clinical and quality interventions. Methods: A team of 6 oncology clinical pharmacists electronically reviewed chemotherapy orders within 9 community oncology practices. The pharmacist identified opportunities to optimize oncology regimens by performing clinical treatment plan reviews, identifying orders requiring dose modifications, symptom management recommendations, clinical consultations, regimen entry, or drug interaction reviews. Recommendations were discussed with the treating provider or modified if permitted by approved practice policies. A retrospective, observational study was performed utilizing clinical intervention data entered by ClinReview pharmacists from October 2022 through March 2023. Interventions were allocated to specific cost-avoidance values based on previously validated studies and extrapolated to an annualized value. Results: During the 6-month study period, a total of 10,195 interventions were documented and categorized as treatment plan management (2,434, 24%), medication regimen/dosing change (6,365, 62%), symptom management (1,145, 11%), drug information consultation (103, 1%), regimen entry, (69, 1%), and drug interaction management (90, 1%). Based on previously validated cost-savings estimates, annualized cost avoidance realized from the ClinReview program was $2,247,818. Taking into account the cost of pharmacist time, the 6-month intervention data demonstrated an annualized net cost-avoidance of $1,896,164. Conclusions: The integration of the ClinReview program into community oncology practices delivers significant quality, safety, and financial benefits, with approximately $1.9 million in annual net cost-savings benefit. [Table: see text]

Pharmacist Involvement in Mental Health Treatment

Mental health disorders constitute a significant public health concern, with a growing recognition of the need for integrated, comprehensive approaches to their management and treatment. Pharmacists, as essential members of the healthcare team, have a unique opportunity to contribute to the care of patients with mental health conditions. This review critically examines the multifaceted role of pharmacists in mental health treatment, encompassing their involvement in medication management, patient education, and collaborative care models. Pharmacists play a pivotal role in ensuring the safe and effective use of psychotropic medications, offering expertise in drug selection, dosing, monitoring, and assessing medication adherence. Their involvement in medication reconciliation and management of drug interactions can significantly enhance patient safety and optimize treatment outcomes. Moreover, pharmacists can provide valuable education to patients and caregivers regarding medication adherence, potential side effects, and strategies for managing adverse reactions, thereby promoting medication compliance and improving overall treatment efficacy. Furthermore, the integration of pharmacists within collaborative care teams has demonstrated promising outcomes in the delivery of holistic mental health services. Through their interdisciplinary collaboration, pharmacists facilitate effective communication among healthcare providers, enabling comprehensive treatment planning and the identification of potential pharmacotherapeutic interventions. This collaborative approach fosters a patient- centered care model, emphasizing the importance of individualized treatment plans tailored to each patient’s unique needs and preferences. Additionally, the expanding role of pharmacists in mental health screenings, early intervention initiatives, and community-based support programs serves to promote mental health awareness and reduce the stigma associated with mental illness. By actively engaging with patients and communities, pharmacists contribute to the development of accessible mental health services and resources, thereby fostering a more inclusive and supportive healthcare environment.

Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions.

Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug-drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug-drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug-drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.

Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis.

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%-115%); tolbutamide, 80% (74%-86%); omeprazole, 55% (47%-65%); dextromethorphan, 77% (68%-86%); midazolam, 62% (49%-78%), and 117% (105%-130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.

Optimizing Pharmacotherapy for Direct Oral Anticoagulants in Older Adults: Strategies for Managing Drug Interactions.

Direct oral anticoagulants (DOACs) have been increasingly used by older adults. Although these medications offer several therapeutic advantages over traditional anticoagulants, such as warfarin, they have limitations. One significant concern associated with DOACs is their potential for drug-drug interactions. These interactions may compromise the safe and effective use of DOACs and can potentially lead to serious adverse events and complications, particularly major bleeding. Polypharmacy is common among older adults with chronic diseases, which can increase the risk of drug-drug interactions with DOACs. The current article discusses the impact and risks of drug-drug interactions with DOACs in the context of older adults and explores ways to improve and manage these interactions through the collaboration of an interprofessional team. [Journal of Gerontological Nursing, 49(9), 7-13.].

Antimicrobials in patients with hematologic malignancies and recipients of hematopoietic cell transplantation and other cellular therapies.

Appropriate use of antimicrobials for hematologic malignancy, hematopoietic stem cell transplant recipients, and other cellular therapies is vital, with infection causing significant morbidity and mortality in this unique population of immunocompromised hosts. However, often in this population the choice and management of antimicrobial therapy is complex. When selecting an antimicrobial agent, key considerations include the need for dose adjustments due to renal or hepatic impairment, managing drug interactions, the potential for additive drug toxicity among those receiving polypharmacy and therapeutic drug monitoring. Other factors include leveraging pharmacodynamic principles to enable optimization of directed therapy against challenging pathogens, as well as judicious use of antimicrobials to limit drug resistance and adverse drug reactions. This review summarizes the clinical considerations for commonly used antimicrobials in this setting, including antibacterial, antiviral, and antifungal agents.