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Clinical Pharmacology in Drug... Mar 2022Omecamtiv mecarbil (OM), a novel cardiac myosin activator, is being evaluated for the treatment of heart failure with reduced ejection fraction. In vitro studies...
Omecamtiv mecarbil (OM), a novel cardiac myosin activator, is being evaluated for the treatment of heart failure with reduced ejection fraction. In vitro studies demonstrate OM as a substrate and inhibitor of P-glycoprotein (P-gp), which can result in drug-drug interactions. Two phase 1, open-label studies assessed the effect of coadministration of OM (50-mg single dose) on the pharmacokinetics of digoxin (0.5-mg single dose; N = 15), a P-gp substrate, and the effect of coadministration of amiodarone (600-mg single dose), a P-gp inhibitor, on the pharmacokinetics of OM (50-mg single dose; N = 14) in healthy subjects. The ratios of the geometric least squares mean (90% confidence interval [CI]) of digoxin coadministered with OM vs digoxin alone for area under the plasma concentration-time curve (AUC) from time 0 to infinity, AUC from time 0 to the time of the last quantifiable concentration, and maximum observed plasma concentration were 1.06 (90%CI, 0.99-1.14), 1.06 (90%CI, 0.98-1.14), and 1.08 (90%CI, 0.92-1.26), respectively. The ratios of the geometric least squares mean of OM coadministered with amiodarone vs OM alone for AUC from time 0 to infinity, AUC from time 0 to the time of the last quantifiable concentration, and maximum observed plasma concentration were 1.21 (90%CI, 1.08-1.36), 1.21 (90%CI, 1.07-1.36), and 1.08 (90%CI, 0.96-1.22), respectively. In conclusion, OM coadministered with digoxin or amiodarone did not result in any clinically relevant pharmacokinetic drug-drug interactions.
Topics: Amiodarone; Clinical Trials, Phase I as Topic; Digoxin; Drug Interactions; Healthy Volunteers; Humans; Urea
PubMed: 34634185
DOI: 10.1002/cpdd.1028 -
Journal of Food and Drug Analysis Apr 2018Medicinal herbs have been a part of human medicine for thousands of years. The herb-drug interaction is an extension of drug-drug interaction, in which the consumptions... (Review)
Review
Medicinal herbs have been a part of human medicine for thousands of years. The herb-drug interaction is an extension of drug-drug interaction, in which the consumptions of herbs cause alterations in the metabolism of drugs the patients happen to take at the same time. The pregnane X receptor (PXR) has been established as one of the most important transcriptional factors that regulate the expression of phase I enzymes, phase II enzymes, and drug transporters in the xenobiotic responses. Since its initial discovery, PXR has been implicated in multiple herb-drug interactions that can lead to alterations of the drug's pharmacokinetic properties and cause fluctuating therapeutic efficacies, possibly leading to complications. Regions of the world that heavily incorporate herbalism into their primary health care and people turning to alternative medicines as a personal choice could be at risk for adverse reactions or unintended results from these interactions. This article is intended to highlight our understanding of the PXR-mediated herb-drug interactions.
Topics: Animals; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Plants, Medicinal; Pregnane X Receptor
PubMed: 29703383
DOI: 10.1016/j.jfda.2017.11.007 -
Journal of Food and Drug Analysis Apr 2016Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson...
Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome (SJS) associated with combination drug administration. Therefore, we studied the relationship between drug combinations and SJS-related mortality, with the hope that a retrospective study of this nature would provide information crucial for the prevention of future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification 695.1) from the National Health Insurance database in Taiwan. Statistical comparisons of the results were performed using analysis of variance (ANOVA), independent sample t-tests, and odds ratio (OR). In this way, the relationship between combinations of SJS-inducing drugs and mortality could be determined. A total of 111 patients who had died, including 63 males and 48 females (66.0 ± 20 and 70.0 ± 17.7 years, respectively), were suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p = 0.049), carbamazepine and sulfamethoxazole/trimethoprim (TMP) (p < 0.0001), carbamazepine and phenytoin (p < 0.0001), sulfamethoxazole/TMP and phenytoin (p = 0.015), sulfadoxine and piroxicam (p = 0.045), phenobarbital and cephalexin (p < 0.0001), ampicillin and erythromycin (p < 0.0001), erythromycin and minocycline (p < 0.0001), and vancomycin and ethambutol (p < 0.0001) administered 1 month before the patients' deaths. Caution should be exercised when administering any drugs that may possibly induce SJS. In addition, attention should be paid to ensure prompt identification of possible drug-drug interactions, and patients should be closely monitored. Furthermore, medications should be immediately discontinued at the first sign or symptom suggesting the occurrence of drug-related SJS, and then prompt, adequate supportive care should be provided.
Topics: Aged; Drug Interactions; Female; Humans; Longitudinal Studies; Male; Retrospective Studies; Stevens-Johnson Syndrome; Taiwan
PubMed: 28911598
DOI: 10.1016/j.jfda.2015.11.009 -
Molecules (Basel, Switzerland) Sep 2021Membrane transporters play an important role in the absorption, distribution, metabolism, and excretion of xenobiotic substrates, as well as endogenous compounds. The... (Review)
Review
Membrane transporters play an important role in the absorption, distribution, metabolism, and excretion of xenobiotic substrates, as well as endogenous compounds. The evaluation of transporter-mediated drug-drug interactions (DDIs) is an important consideration during the drug development process and can guide the safe use of polypharmacy regimens in clinical practice. In recent years, several endogenous substrates of drug transporters have been identified as potential biomarkers for predicting changes in drug transport function and the potential for DDIs associated with drug candidates in early phases of drug development. These biomarker-driven investigations have been applied in both preclinical and clinical studies and proposed as a predictive strategy that can be supplanted in order to conduct prospective DDIs trials. Here we provide an overview of this rapidly emerging field, with particular emphasis on endogenous biomarkers recently proposed for clinically relevant uptake transporters.
Topics: Animals; Biological Transport; Drug Interactions; Humans; Membrane Transport Proteins
PubMed: 34576971
DOI: 10.3390/molecules26185500 -
JMIR MHealth and UHealth Jun 2021As a computerized drug-drug interaction (DDI) alert system has not been widely implemented in China, health care providers are relying on mobile health (mHealth) apps as...
BACKGROUND
As a computerized drug-drug interaction (DDI) alert system has not been widely implemented in China, health care providers are relying on mobile health (mHealth) apps as references for checking drug information, including DDIs.
OBJECTIVE
The main objective of this study was to evaluate the quality and content of mHealth apps supporting DDI checking in Chinese app stores.
METHODS
A systematic review was carried out in November 2020 to identify mHealth apps providing DDI checking in both Chinese iOS and Android platforms. We extracted the apps' general information (including the developer, operating system, costs, release date, size, number of downloads, and average rating), scientific or clinical basis, and accountability, based on a multidimensional framework for evaluation of apps. The quality of mHealth apps was evaluated by using the Mobile App Rating Scale (MARS). Descriptive statistics, including numbers and percentages, were calculated to describe the characteristics of the apps. For each app selected for evaluation, the section-specific MARS scores were calculated by taking the arithmetic mean, while the overall MARS score was described as the arithmetic mean of the section scores. In addition, the Cohen kappa (κ) statistic was used to evaluate the interrater agreement.
RESULTS
A total of 7 apps met the selection criteria, and only 3 included citations. The average rating score for Android apps was 3.5, with a minimum of 1.0 and a maximum of 4.9, while the average rating score for iOS apps was 4.7, with a minimum of 4.2 and a maximum of 4.9. The mean MARS score was 3.69 out of 5 (95% CI 3.34-4.04), with the lowest score of 1.96 for Medication Guidelines and the highest score of 4.27 for MCDEX mobile. The greatest variation was observed in the information section, which ranged from 1.41 to 4.60. The functionality section showed the highest mean score of 4.05 (95% CI 3.71-4.40), whereas the engagement section resulted in the lowest average score of 3.16 (95% CI 2.81-3.51). For the information quality section, which was the focus of this analysis, the average score was 3.42, with the MCDEX mobile app having the highest score of 4.6 and the Medication Guidelines app having the lowest score of 1.9. For the overall MARS score, the Cohen interrater κ was 0.354 (95% CI 0.236-0.473), the Fleiss κ was 0.353 (95% CI, 0.234-0.472), and the Krippendorff α was 0.356 (95% CI 0.237-0.475).
CONCLUSIONS
This study systematically reviewed the mHealth apps in China with a DDI check feature. The majority of investigated apps demonstrated high quality with accurate and comprehensive information on DDIs. However, a few of the apps that had a massive number of downloads in the Chinese market provided incorrect information. Given these apps might be used by health care providers for checking potential DDIs, this creates a substantial threat to patient safety.
Topics: China; Delivery of Health Care; Drug Interactions; Humans; Mobile Applications; Pharmaceutical Preparations
PubMed: 33962910
DOI: 10.2196/26262 -
Biomedicine & Pharmacotherapy =... Jul 2023Polypharmacy is becoming increasingly prevalent in society. Patients with polypharmacy are at greater risk for drug-drug interactions, which can influence the efficacy...
Polypharmacy is becoming increasingly prevalent in society. Patients with polypharmacy are at greater risk for drug-drug interactions, which can influence the efficacy of treatment. Especially, in oncology this is a concern since neoplasms are increasing prevalent with age, as well as polypharmacy is. Besides drug-drug interactions, also herb-drug and food-drug interactions could be present. Knowledge of these interactions is of great importance for safe and effective anti-cancer treatment, because the therapeutic window of most of these oncologic drugs are small. To study pharmacokinetic interaction effects, a cross-over pharmacokinetic study is a widely used, efficient and scientifically robust design. Yet, several aspects need to be considered when carrying out an interaction study. This includes the knowledge of the advantages and disadvantages of a cross-over design. Furthermore, determination of the end point and research question of interest, calculation of the required sample size, analysis of the generated data with a robust statistical plan and consideration of the logtransformation for some pharmacokinetic parameters are important aspects to consider. Even though some guidelines exist regarding these key issues, no clear overview exists. In this article an overview of these aspects is provided and their effect is discussed.
Topics: Humans; Drug Interactions; Food-Drug Interactions; Herb-Drug Interactions; Neoplasms; Polypharmacy; Cross-Over Studies
PubMed: 37172331
DOI: 10.1016/j.biopha.2023.114823 -
Clinical and Translational Science Jun 2023It is well-recognized that therapeutic proteins (TPs) with pro-inflammatory activities elevate the pro-inflammatory cytokines and result in cytokine-drug interactions.... (Review)
Review
It is well-recognized that therapeutic proteins (TPs) with pro-inflammatory activities elevate the pro-inflammatory cytokines and result in cytokine-drug interactions. In the current review, several pro-inflammatory cytokines, including IL-2, IL-6, IFN-γ, and TNF-α, as well as an anti-inflammatory cytokine IL-10, were summarized for their respective effect on major cytochrome P450 enzymes and efflux transporter PgP. Pro-inflammatory cytokines are generally associated with suppression of CYP enzymes across assay systems but have varied effect on Pgp expression levels and activities depending on the individual cytokines and assay systems, whereas IL-10 had no significant impact on CYP enzymes and P-gp. A cocktail drug-drug interaction (DDI) study design could be an ideal approach for simultaneously assess the impact of TPs with pro-inflammatory activities on multiple CYP enzymes. Clinical DDI studies using the cocktail approach have been conducted for several TPs with pro-inflammatory activities and for those TPs with pro-inflammatory activities which had no clinical DDI study conducted, languages for potential DDI risk due to cytokine-drug interaction were included in the label. Up to date drug cocktails, including clinically validated and unvalidated for DDI assessment, were summarized in this review. Most clinically validated cocktails focused either on CYP enzymes or transporters. Additional effort was needed to validate a cocktail to include both the major CYP enzymes and key transporters. In silico methods for assessment of the DDI for TPs with pro-inflammatory activities were also discussed.
Topics: Humans; Interleukin-10; Cytochrome P-450 Enzyme System; Cytokines; Drug Interactions
PubMed: 36890677
DOI: 10.1111/cts.13507 -
Revue Medicale de Liege Jun 2024Adverse events related to drug therapy are a major cause of iatrogenicity. They are responsible of increased morbidity, leading to hospitalization, sometimes in... (Review)
Review
Adverse events related to drug therapy are a major cause of iatrogenicity. They are responsible of increased morbidity, leading to hospitalization, sometimes in emergency, and mortality, not only in ambulatory care but also during hospitalization itself. Causes are multiple : among them, confusion leading to an erroneous drug administration, mistakes regarding dosage, risks associated to self-medication, drug-drug interactions or even food-drug interactions. Elderly population is exposed to an increased incidence of drug iatrogenicity because older patients cumulate numerous risk factors, especially polypharmacy and cognitive disorders. Prevention of drug iatrogenicity is a key objective from a public health point of view. Preventive measures should target the prescriber (physician), the dispenser (pharmacist), the user (patient) and the supplier (pharmaceutical industry).
Topics: Humans; Iatrogenic Disease; Drug-Related Side Effects and Adverse Reactions; Medication Errors; Drug Interactions; Risk Factors
PubMed: 38869139
DOI: No ID Found -
Journal of the National Medical... Oct 1978Self-medication and drug interaction have been a problem in recent years. Pharmacists in ethical pharmacies and neighborhood establishments can best monitor these...
Self-medication and drug interaction have been a problem in recent years. Pharmacists in ethical pharmacies and neighborhood establishments can best monitor these problems through use of patient profile records and consultations. The pharmacist should advise the public on over-the-counter (OTC) purchases. Auxiliary labels are recommended for use on containers to prevent drug interactions. Members of the black community have some specific problems with respect to self medications. These are addressed in this article. Self-medication, under supervision, is proper and can be controlled.
Topics: Drug Interactions; Drug Labeling; Health Education; Humans; Pharmaceutical Preparations; Pharmacists; Referral and Consultation; Self Medication
PubMed: 712861
DOI: No ID Found -
BMC Medical Informatics and Decision... Feb 2022Clinical decision support systems are implemented in many hospitals to prevent medication errors and associated harm. They are however associated with a high burden of...
BACKGROUND
Clinical decision support systems are implemented in many hospitals to prevent medication errors and associated harm. They are however associated with a high burden of false positive alerts and alert fatigue. The aim of this study was to evaluate a drug-drug interaction (DDI) clinical decision support system in terms of its performance, uptake and user satisfaction and to identify barriers and opportunities for improvement.
METHODS
A quantitative evaluation and end-user survey were performed in a large teaching hospital. First, very severe DDI alerts generated between 2019 and 2021 were evaluated retrospectively. Data collection comprised alert burden, override rates, the number of alert overrides reviewed by pharmacists and the resulting pharmacist recommendations as well as their acceptance rate. Second, an e-survey was carried out among prescribers to assess satisfaction, usefulness and relevance of DDI alerts as well as reasons for overriding.
RESULTS
A total of 38,409 very severe DDI alerts were generated, of which 88.2% were overridden by the prescriber. In 3.2% of reviewed overrides, a recommendation by the pharmacist was provided, of which 79.2% was accepted. False positive alerts were caused by a too broad screening interval and lack of incorporation of patient-specific characteristics, such as QTc values. Co-prescribing of a non-vitamin K oral anticoagulant and a low molecular weight heparin accounted for 49.8% of alerts, of which 92.2% were overridden. In 88 (1.1%) of these overridden alerts, concurrent therapy was still present. Despite the high override rate, the e-survey revealed that the DDI clinical decision support system was found useful by prescribers.
CONCLUSIONS
Identified barriers were the lack of DDI-specific screening intervals and inclusion of patient-specific characteristics, both leading to a high number of false positive alerts and risk for alert fatigue. Despite these barriers, the added value of the DDI clinical decision support system was recognized by prescribers. Hence, integration of DDI-specific screening intervals and patient-specific characteristics is warranted to improve the performance of the DDI software.
Topics: Decision Support Systems, Clinical; Drug Interactions; Humans; Medical Order Entry Systems; Medication Errors; Retrospective Studies
PubMed: 35193547
DOI: 10.1186/s12911-022-01783-z