Clinical Relevance Of Drug Interactions Research Articles

Clinical Relevance of Drug Interactions in People Living with Human Immunodeficiency Virus on Antiretroviral Therapy-Update 2022: Systematic Review.

The clinical outcomes of antiretroviral drugs may be modified through drug interactions; thus, it is important to update the drug interactions in people living with HIV (PLHIV). To update clinically relevant drug interactions in PLHIV on antiretroviral therapy with novel drug interactions published from 2017 to 2022. A systematic review in Medline/PubMed database from July 2017 to December 2022 using the Mesh terms antiretroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full-text access were retrieved. The clinical relevance of drug interactions was grouped into five levels according to the gravity and probability of occurrence. A total of 366 articles were identified, with 219 (including 87 citation lists) were included, which allowed for the identification of 471 drug interaction pairs; among them, 291 were systematically reported for the first time. In total 42 (14.4%) and 137 (47.1%) were level one and two, respectively, and 233 (80.1%) pairs were explained with the pharmacokinetic mechanism. Among these 291 pairs, protease inhibitors (PIs) and ritonavir/cobicistat-boosted PIs, as well as integrase strand transfer inhibitors (InSTIs), with 70 (24.1%) and 65 (22.3%) drug interaction pairs of levels one and two, respectively, were more frequent. In PLHIV on antiretroviral therapy, we identify 291 drug interaction pairs systematically reported for the first time, with 179 (61.5%) being assessed as clinically relevant (levels one and two). The pharmacokinetic mechanism was the most frequently identified. PIs, ritonavir/cobicistat-boosted PIs, and InSTIs were the antiretroviral groups with the highest number of clinically relevant drug interaction pairs (levels one and two).

Cannabidiol-drug interaction in cancer patients: A retrospective study in a real-life setting.

Cannabidiol (CBD) consumption in cancer patients is growing and there is a need to investigate how to detect cannabidiol-drug interactions (CDIs). However, CDIs and the clinical relevance between CBD, anticancer treatment, supportive care and conventional drugs is poorly studied especially in real-life settings. In 1 oncology day-hospital, a cross-sectional study in 363 cancer patients treated with chemotherapy revealed 20 patients (5.5%) who consumed CBD. In this study we aimed to explore the prevalence and clinical relevance of CDIs among these 20 patients. CDI detection used the Food and Drug Administration Drugs.com database and clinical relevance was assessed accordingly. Ninety CDIs with 34 medicines were detected (4.6 CDI/patient). The main clinical risks were central nervous system depression and hepatoxicity. The main CDIs were assessed as moderate and anticancer treatment do not seem to add to the risk. CBD discontinuation appears to be the most consistent management. Future studies should explore the clinical relevance of drug interactions with CBD in cancer patients.

Clinical Relevance of Drug Interactions with Cannabis: A Systematic Review.

Concomitant use of cannabis with other drugs may lead to cannabis–drug interactions, mainly due to the pharmacokinetic mechanism involving the family of CYP450 isoenzymes. This narrative systematic review aimed to systematize the available information regarding clinical relevance of cannabis–drug interactions. We utilized the PubMed/Medline database for this systematic review, using the terms drug interactions and cannabis, between June 2011 and June 2021. Articles with cannabis–drug interactions in humans, in English or Spanish, with full-text access were selected. Two researchers evaluated the article’s inclusion. The level of clinical relevance was determined according to the severity and probability of the interaction. Ninety-five articles were identified and twenty-six were included. Overall, 19 pairs of drug interactions with medicinal or recreational cannabis were identified in humans. According to severity and probability, 1, 2, 12, and 4 pairs of cannabis–drug interactions were classified at levels 1 (very high risk), 2 (high risk), 3 (medium risk), and 5 (without risk), respectively. Cannabis–warfarin was classified at level 1, and cannabis–buprenorphine and tacrolimus at level 2. This review provides evidence for both the low probability of the occurrence of clinically relevant drug interactions and the lack of evidence regarding cannabis–drug interactions.

Clinical relevance of drug interactions: Proposal to update the classification based on the severity and probability of its occurrence

Clinical relevance of drug interactions: Proposal to update the classification based on the severity and probability of its occurrence

The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2015-2017

The pharmacokinetics of anti-retrovirals (ARVs) can be modified by other concomitant medicinal products. It is timely to update the interactions between new ARVs and drugs of chronic use to maintain therapeutic success. To update information about drug interactions in patients with HIV/AIDS on antiretroviral therapy. Comprehensive literature review in MEDLINE/PubMed database from January of 2015 to June of 2017, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into levels according to seriously and probability of occurrence. 466 articles were identified; full text was accessed in 444. Of these, 164 provided interactions, which allowed the identification of a total of 534 pairs of drug interactions. The interactions that presented a higher risk of generating safety and effectiveness problems were 308 (57.7%) of level 2 and 35 (6.6%) of level 1. We identify 534 new pairs of drug interactions, of which 308 (64.2%) are the most clinically relevant.

Aproximación para establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes infectados con virus de hepatitis C, revisión estructurada (actualización 2015 – 2017)

Objetivo: establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes con hepatitis C.
 Método: se realizó una búsqueda en PubMed/MedLine de artículos publicados en inglés y en español, desde el 1 de enero de 2015 hasta el 30 de marzo de 2017, utilizando los términos Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, de estudios realizados en humanos. La relevancia clínica de las interacciones medicamentosas se estableció y evaluó con base en la probabilidad de ocurrencia y la gravedad de la interacción.
 Resultados: se identificaron 184 artículos, de los cuales 92 se seleccionaron por el título y resumen para revisión completa, a 2 de ellos no fue posible acceder al texto completo. De estos, 57 aportaban interacciones, lo que permitió identificar 155 parejas de interacciones medicamentosas, de las cuales 154 (99,4 %) fueron farmacocinéticas y 1 (0,6 %) farmacodinámica. Por su parte, de las 155 parejas, 34 (21,9 %) se valoraron de nivel 1; 73 (47,1 %) de nivel 2; 48 (31,0 %) de nivel 3; y 0 (0,0 %) de nivel 4. Además, se identificaron 29 parejas agrupadas como interacciones con evidencia de ausencia de relevancia clínica.
 Conclusiones: más de 99 % de las interacciones medicamentosas de relevancia clínica son farmacocinéticas, asociadas con cambios en el metabolismo y el transporte de fármacos; el simeprevir y la terapia 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) fueron los medicamentos con mayor número de interacciones.

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Introduction: drug interactions of anti-infectives can trigger renal disease; however, information on this effect is limited. Therefore, the identification, prevention and management of clinically relevant drug interactions are a key aspect in the achievement of therapeutic objectives in patients receiving anti-infectives. Objective: to identify and assess the clinical relevance of anti-infective drug interactions that causes kidney disease. methodology: systematic qualitative review of drug interactions of anti-infectives associated with renal disease. The clinical relevance of drug interactions was assessed according to the probability of occurrence and severity of the effect. The search was done in the PubMed/Medline database of articles published in english or spanish, between august 2006 and august 2016, using the following Mesh terms and Boolean Operators: “Renal Insufficiency” OR “ Anti-Bacterial Agents “OR” Drug Interactions “OR” HerbDrug Interactions “OR” Food-Drug Interactions “. Results: we identified 44 publications and nine were included. In these nine articles, 12 drug interactions associated with renal disease were identified. Combinations associated with renal disease were protease inhibitors/nifedipine, cobicistat/fenofibrate/pravastatin, tenofovir/metformin, macrolides/statins, statins/calcium channel blockers, quinolones/warfarin, valaciclovir/loxoprofen and fusidic acid/Pravastatin. Conclusions: protease inhibitors, macrolides and quinolones, as well as tenofovir, cobicistat, valaciclovir and fusidic acid can generate renal disease when used simultaneously with other drugs, especially with statins, calcium channel blockers, warfarin, metformin or loxoprofen. MED.UIS. 2017;30(3):101-9

The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014

To update information about drug interactions in patients with HIV/AIDS. Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV®) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS.

Dosing Recommendations of Aripiprazole Depot with Strong Cytochrome P450 3A4 Inhibitors: A Relapse Risk.

A 50-year-old male patient with comorbid human immunodeficiency virus developed a relapse of bipolar disorder after a switch from oral aripiprazole 10 mg/day to intramuscular aripiprazole depot 200 mg every 28 days plus oral aripiprazole 5 mg/day. The patient was concomitantly taking lopinavir, saquinavir, ritonavir, silybum marianum extract, and omeprazole. Only 1 week after the switch, the patient developed mood swings, irritability, depressive mood, and lack of drive. The oral aripiprazole was increased again to stabilize the patient. The measured trough drug concentration of aripiprazole was low and may be correlated to the relapse. When oral aripiprazole was increased back to 10 mg again, the depressive symptoms subsided. The dose of the next depot injection was increased to 300 mg and that of oral aripiprazole decreased back to 5 mg/day. Because trough drug concentrations were still low after 28 days, the depot dose was increased to 400 mg every 28 days, which is double that recommended in the prescriber’s information. Two months after the initial switch from oral to intramuscular aripiprazole, the patient’s mood stabilized on aripiprazole depot 400 mg every 28 days. More clinical data, especially regarding the pharmacokinetic drug interactions of aripiprazole depot are needed to improve dosing recommendations, and prevent relapses or adverse drug events. Genetic polymorphisms may play an important role in the clinical relevance of drug interactions concerning aripiprazole depot.

Pharmaceutical intervention assessment in the identification and management of drug interactions in an intensive care unit

It is estimated there are thousands of combinations of drugs, which may generate various adverse drug events, including drug interactions (DI). To assess the contribution of pharmacist to identification and management of DI in an intensive care unit (ICU). A longitudinal study was conducted in the ICU of a private hospital in the city of Aracaju-SE, between 2008 and 2009. The prevalence and clinical relevance of DI was assessed by two clinical pharmacists. Demographic data and clinical information of patients hospitalized in the period of the study were obtained from medical records. At the end of the study 137 medical records were analyzed, with a predominance of female patients (55.4%), average age of 66 (±7.0) years. 6,085 prescriptions were collected during the study period, in which 2,455 drugs prescribed. Of these, 175 prescriptions contained clinically relevant DI, 178 of moderate severity and 35 of major severity, 213 DI in total. The clinical pharmacists prepared reports for the physicians, which enabled the reduction of 40% of all DI. Data from this study suggest that pharmacist’s contribution may have reduced the incidence of DI, providing more familiarity of physicians on clinically relevant information and improving the quality of prescriptions in the ICU.

Relevancia clínica de las interacciones medicamentosas entre antiinflamatorios no esteroideos y antihipertensivos

ObjectiveTo establish the clinical relevance of drug interactions between nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives, based on the interaction severity and probability of occurrence. DesignSystematic review. Data sourcesA PubMed/Medline search was made using the MeSH terms: NSAIDs, Antihypertensive drugs, and Drug interactions. Data extractionArticles between 2002 and 2012, human studies, in Spanish and English and full text access were included. Found articles were included and some of the references used in this works. Studies with in vitro methods, effects on ocular hypertension and those who do not consider the interaction NSAIDs, antihypertensives were excluded. For the selection of the papers included three independent reviewers were involved. We used a tool for data extraction and for assess of the interaction clinical relevance. ResultsNineteen of 50 papers found were included. There were identified 21 interactions with pharmacodynamic mechanism, classified by their clinical relevance in level-2 high risk (76.2%) and level-3 medium risk (23.8%). In addition, evidence of 16 combinations of no interaction were found. ConclusionsSome NSAIDs may attenuate the effectiveness of antihypertensive drugs when used concurrently, especially with angiotensin converting enzyme inhibitors, diuretics, beta blockers and angiotensin receptorsii blockers. There was no evidence of effect modification of calcium channel antagonists, especially dihydropyridine, by concurrent use of NSAIDs.

The incidence and clinical relevance of drug interactions in pediatrics.

Objective:To investigate the prevalence of the major drug interactions in children and verify the rate and profile of drug interactions in hospitalized pediatric patients.Materials and Methods:A retrospective study was designed and data collected from the files of hospitalized children in Pulmonology, Nephrology, and Gastroenterology wards of a Pediatric Clinic, from July 1999 to 2004.Results:From the analyzed material, we detected 34 cases of interactions, of which 1 was pharmacodynamics interaction, 13 were pharmacokinetic interactions, and 20 of unknown mechanisms. According to the rate of significance, 4 cases were categorized in the first significance rate of interaction, 18 cases in the second significance rate, 1 case of the third significance rate, 4 cases of the fourth significance rate, and 7 cases of the fifth significance rate. According to onset of cases, 33 cases were of delayed onset, and according to severity of interactions, in 7 cases we noticed major severity interaction, in 19 cases moderate severity and in 8 cases minor severity.Conclusions:The presence of drug interactions is a permanent risk in the pediatric clinic. Then, we can conclude that continued education, computer system for prescriptions, pharmacotherapy monitoring of patients, and the pharmacist participation in the multidisciplinary team are some manners of improving the treatment to hospitalized patients.

Evaluation of Drug Interactions in a Large Sample of Psychiatric Inpatients: A Data Interface for Mass Analysis With Clinical Decision Support Software

In order to improve medication safety, more epidemiological data on the prevalence and clinical relevance of drug interactions are required. We developed an interface for mass analysis using the Clinical Decision Support Software (CDSS) MediQ and a multidimensional classification (Zurich Interaction System (ZHIAS)) incorporating the Operational Classification of Drug Interactions (ORCA). These were applied to 359,207 cross-sectional prescriptions from 84,607 psychiatric inpatients collected through the international AMSP program. MediQ issued 2,308 "high" and 71,112 "average" danger interaction alerts. Among these, after ORCA reclassification, there were 151 contraindicated and 4,099 provisionally contraindicated prescriptions. The ZHIAS provided further detailed categorical information on recommended management and specific increased risks (QTc prolongation being the most frequent one) associated with interactions. We developed a highly efficient solution for the identification and classification of drug interactions in large prescription data sets; this solution may help to reduce the frequency of overalerting and improve acceptance of the efficacy of CDSS in reducing the occurrence of potentially harmful drug interactions.

Predicting the Clinical Relevance of Drug Interactions From Pre-Approval Studies

Drug interactions (DIs) may result in adverse drug events that could be prevented, but in many cases the available information on potential DIs is not easily transferable to clinical practice. The majority of studies date from preclinical or premarketing phases, using animals or human-derived sources that may not accurately reflect the growing clinical complexity of high-risk populations, such as the elderly, women, children, patients with chronic disease, polytherapy and impaired organ functions. Thus, at the time of approval of a new drug the information in the summary of product characteristics refers to potential DIs, but lacks specific management recommendations and is of limited clinical utility. Therefore, we set out to review in vitro and in vivo methods to predict and quantify potential DIs, to see whether these studies could help the physician tackle daily problems of the assessment and choice of combined drug therapies, and to propose, from a clinical point of view, how premarketing studies could be improved so as to help the physician at the patient's bedside. Preclinical and premarketing study design needs to be improved to make information easily accessible and clinically transferable. Studies should also take into account appropriate sample size, duration, co-morbidity, number of coadministered drugs, within- and between-subject variability, specific at-risk populations and/or drugs with a relatively narrow therapeutic window, and clinical endpoints. After premarketing development in situations where there is potential high risk of serious adverse events, specific phase IV studies (and/or active pharmacovigilance studies) should be required to monitor and quantitatively assess their clinical impact.

Frequency and Clinical Relevance of Drug Interactions with Lovastatin and Simvastatin

Concomitantly used cytochrome P450 (CYP) 3A4 inhibitors and inducers have been shown to alter the plasma concentrations of the HMG-CoA reductase inhibitors ('statins') lovastatin and simvastatin. Myopathy is a serious adverse effect of statins. Concurrent use of statins with fibrates in particular seems to increase the risk of this adverse effect. To evaluate the incidence and clinical consequences of the use of lovastatin or simvastatin with concomitant CYP3A4 inhibitors and inducers, and with fibrates. An observational database study of hospitalized patients treated in Turku University Hospital, Turku, Finland, covering the period 1 July 1996 to 30 June 2003, and of nationwide community data from the Finnish Prescription Register over the period 1 April to 30 June 2001 was conducted. In the hospital setting, the study population comprised 71 025 patients (93 467 treatment periods) over 7 years, with a total of 5320 treatment periods of lovastatin or simvastatin. The community-based, nationwide survey included all reimbursed prescriptions of lovastatin and simvastatin (n = 91 656) in Finland during a 3-month period. The frequency of drug-drug interactions involving lovastatin or simvastatin was studied. The efficacy and safety of the various statin/concomitant drug combinations was estimated by evaluating patients' laboratory data. Concomitant use of lovastatin or simvastatin with interacting medication was detected in 13.3% (704) and 6.9% (6338) of patients in hospital and community settings, respectively. Co-administration of lovastatin or simvastatin with CYP3A4 inhibitors or inducers did not have a clinically significant effect on serum lipid values. Plasma creatine kinase (CK) activity was significantly higher in patients receiving a statin and a fibrate compared with a statin only (433 U/L vs 209 U/L, p = 0.053). Co-administration of a statin and a CYP3A4 inhibitor did not increase CK activity. Although the pharmacokinetic interactions between lovastatin or simvastatin and CYP3A4 inhibitors and inducers are substantial, their clinical relevance seems to be limited, at least with lower statin doses. However, combining statins with fibrates, especially gemfibrozil, clearly increases the potential for muscular toxicity.

Comparative assessment of four drug interaction compendia

To assess the consistency of inclusion and grading of major drug interactions for 50 drugs in four leading international drug interaction compendia. METHODS Four international drug interaction compendia were compared: the drug interactions appendix of the British National Formulary, the interaction supplement in the French drug compendium Vidal, and two US drug interaction compendia, Drug Interaction Facts and the Micromedex (Drug-Reax) program. Major interactions were defined as potentially hazardous in BNF or with the warning 'contraindication' or 'avoid' in Vidal or with the significance grading 1 or 2 in DIF. Major interactions for a list of 50 drugs were searched in all four compendia. A total of 1264 interactions meeting the inclusion criteria were identified for these 50 drugs. After deletion of 169 duplicates, 1095 interactions were included in the analysis. Of the drug interactions classified as major in any one compendium between 14% and 44% were not listed in the other compendia. The grading systems used for the severity and the quality of the supporting evidence in Micromedex and DIF were inconsistent. There is a lack of consistency in the inclusion and grading of drug interactions of major significance for 50 drugs across the four drug compendia examined. This may reflect the lack of standardization of the terminology used to classify drug interactions and the lack of good epidemiological evidence on which to base the assessment of the clinical relevance of drug interactions.

Arzneimittelinteraktionen antimikrobieller Substanzen bei Kindern und Jugendlichen

Antimicrobial agents are among the most common therapeutics prescribed to children and adolescents with hematologic/oncologic disorders. Because of the polymorbid state of most patients, they are frequently administered concomitantly with other drugs, resulting in a considerable potential for drug interactions. While many of these interactions are of marginal clinical significance, others are associated with substantial risks of decreased therapeutic efficacy or increased drug toxicity. Prevention and recognition of drug interactions are therefore of vital importance to optimizing effective use of antimicrobials and enhancing patient outcome. Key to minimize drug interactions are a thorough understanding of the pharmacology of frequently used antimicrobial agents and a careful evaluation of risks and benefits of potentially interacting drugs. This article reviews mechanisms and clinical relevance of drug interactions of antimicrobial agents in the supportive care of children and adolescents with hematologic/oncologic disorders and provides strategies for their prevention.

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Update on drug interactions with azole antifungal agents.

To review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and fluconazole. Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term "interaction" as MeSH headings. Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1996. Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included. In vitro data were selected from literature review and citations. Data were evaluated with respect to study design, clinical relevance, magnitude of interaction, and recommendations provided. The incidence of fungal infections and consequent azole antifungal usage continues to increase. By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles have been investigated and implicated in several drug interactions. The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant. The azole antifungal agents represent a commonly used class of agents with a broad range of potential interactions. Recent data have increased our understanding of drug--drug interactions with azoles. Pharmacists are in a unique position to identify these interactions and to intervene to decrease their morbidity and improve patient care.