Concomitant Use Of Multiple Drugs Research Articles

Opioid metabolism and drug-drug interaction in cancer.

Concomitant use of multiple drugs in most patients with cancer may result in drug-drug interactions (DDIs), potentially causing serious adverse effects. These patients often experience unrelieved cancer-related pain (CRP) during and after cancer treatment, which can lead to a reduced quality of life. Opioids can be used as part of a multimodal pain management strategy when non-opioid analgesics are not providing adequate pain relief, not tolerated, or are contraindicated. However, due to their narrow therapeutic window, opioids are more susceptible to adverse events when a DDI occurs. Clinically relevant DDIs with opioids are usually pharmacokinetic, mainly occurring via metabolism by cytochrome P450 (CYP). This article aims to provide an overview of potential DDIs with opioids often used in the treatment of moderate-to-severe CRP and commonly used anticancer drugs such as chemotherapeutics, tyrosine kinase inhibitors (TKIs), or biologics. A DDI-checker tool was used to contextualize the tool-informed DDI assessment outcomes with clinical implications and practice. The findings were compared to observations from a literature search conducted in Embase and PubMed to identify clinical evidence for these potential DDIs. The limited results mainly included case studies and retrospective reviews. Some potential DDIs on the DDI-checker were aligned with literature findings, while others were contradictory. In conclusion, while DDI-checkers are useful tools in identifying potential DDIs, it is necessary to incorporate literature verification and comprehensive clinical assessment of the patient before implementing tool-informed decisions in clinical practice.

Interaction between Food and Anticoagulants in Patients with Cardiovascular Diseases

Cardiovascular diseases are one of the most common diseases in the world. Anticoagulants and other drugs are prescribed as a treatment for these diseases. However, polypharmacy may increase the risk of drug-drug or food-drug interactions and decrease patient compliance. Food-drug interactions may put the patient at risk for serious adverse effects and reduce the safety and efficacy of treatment. Food‐drug interaction is a common problem that has occurred as a result of the concomitant use of multiple drugs with food. Food-drug interaction is the term used to describe how food affects a medication in the body. Food can alter the effectiveness of the medication, make unwanted side effects better or worse, or even bring on brand-new negative effects. Drugs may alter how the body processes food. Consumption of foods that contain vitamin K makes anticoagulant therapy less effective. On the other hand, patients should be careful when consuming foods like garlic, ginseng, ginger, and ginkgo to avoid the undesirable effect of hemorrhage. Among the medical records examined, no advice or recommendations were provided regarding anticoagulant-food interactions, no details about the time of taking anticoagulant drugs and the exact time of eating meals were given and there were few instances in which medicine dosage was altered due to a food association. A majority of patients who completed an anonymous survey in community pharmacies were not informed about food-drug interactions. Healthcare professionals should advise patients taking anticoagulants to be careful with the food they consume and clinicians should manage the time and dose variability of the medicine so a successful therapy can be achieved.

Food-drug Interactions in Patients with Cardiovascular Diseases

Cardiovascular diseases are one of the most common diseases in the world. Anticoagulants and other drugs are prescribed as treatment for these diseases however, polypharmacy may increase the risk of drug-drug or food-drug interatrions and decrease patient compliance. Food-drug interatrions may put the patient at risk for serious adverse effects and reduce safety and efficacy of treatment. Food‐drug interaction is a common problem that has occurred as a result of the concomitant use of multiple drugs with food. Food-drug interaction is the term used to describe how a food affects a medication in the body. Food can alter the effectiveness of medication, make unwanted side effects better or worse, or even bring on brand-new negative effects. Drugs may alter how the body processes food. Consumption of foods which contain vitamin K make anticoagulant therapy less effective. On the other hand, patients should be careful when consuming foods like: garlic, ginseng, ginger and ginkgo in order to avoid the undesirable effect of hemorrhage. Healthcare professionals should advice patients taking anticoagulants to be careful with the food they consume and clinicians should manage the time and dose variability of the medicine so a successful therapy can be achieved.

267P AB-ITALY: The impact of drug-drug interaction on abemaciclib treatment in Italian real world experience

Abemaciclib demonstrated a clinical benefit in women affected by HR+/HER2- metastatic breast cancer (mBC). Drug-drug interactions (DDIs) can lead to a reduced treatment efficacy or increased toxicity. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the crucial role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. This retro-prospective study aimed to evaluate outcomes, toxicities and DDIs of abemaciclib combined with hormone therapy in a real-world setting. Patients (pts) from 12 referral hospitals in Italy, affected by HR+/HER2- mBC who received abemaciclib were included. Availability of clinical data about comorbidities, concurrent medications, outcomes were inclusion criteria. Drug-PIN® was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, orange, and red) for each pt. Univariate and multivariate analysis were performed to identify early predictors of patients PFS, toxicity or best response (BR). A total of 173 pts were included. Abemaciclib was administered in combination with fulvestrant or with aromatase inhibitors in 92 and 81 pts, respectively. Overall response rate (ORR) was 62.8%. The median PFS was 28.8 months.The most common toxicities were diarrhoea, asthenia and neutropenia in 63%,49%,49% of pts respectively. Median Drug-PIN score was 3.25 (range 0 -114.8) and 150, 6, 8, 6 and 3 pts were in the green, yellow, dark yellow, orange and red tier, respectively. At the univariate analysis, the number of drugs (p=0.003), the best response (p<0.0001), the high values of Drug-PIN score (p=0.015) and the Drug-PIN tier (from dark yellow to red, p=0.039) were associated with decreased PFS. Correcting for significant variables found at univariate analysis, only the association between BR (p<0.0001), Drug-PIN tier (dark yellow to red, p=0.007) and decreased PFS were confirmed at the multivariate analysis (p<0.0001). Our study suggests that the concomitant use of multiple drugs is associated with higher toxicity in pts affected by mBC treated with abemaciclib. Moreover, a statistically significant association between decreased PFS and high Drug-PIN score was shown.

PHARMACOVIGILANCE IN THE ERA OF COVID-19: A CONCISE REVIEW OF THE CURRENT SCENARIO, IMPLICATIONS, AND CHALLENGES

The pandemic of Coronavirus Disease 2019 (COVID-19) has now affected the entire globe which was first surfaced in China in December 2019. In absence of effective therapy to manage COVID-19, repurposed therapies were being used to manage the condition. In view of an urgent need for definitive therapy, multiple repurposed drugs, and investigational drug candidates are being tried in clinical trials which may lead to the emergence of unknown short term and long term adverse drug reactions (ADRs), and hence it is crucial to assess the safety of the tried therapeutic interventions. The lag in the pharmacovigilance activities in the midst of this pandemic fosters under-reporting of ADRs. Difficulty in causality assessment due to factors like wide variations in clinical presentation, concomitant use of multiple drugs, associated comorbidities, drug-drug and drug-disease interaction which forestalls the appropriate causality assessment. Hydroxychloroquine, a repurposed antimalarial drug has been a part of hue and cry at present because of its in-question safety in patients with cardiac disorders. National and International Drug monitoring centers have stressed upon reporting of ADRs and to boost up the process and come up with various recommendations. We can overcome these issues by working cohesively, motivating HCPs and patients to report ADRs electronically, and by setting up dedicated pharmacovigilance rapid response team to tackle the issues at the earliest.

Drug-drug Interactions in Patients with HIV and Cancer in Sub-Saharan Africa.

In Sub-Saharan Africa, the cancer burden is predicted to increase by > 85% by 2030, the largest increase worldwide. This region has a large HIV-positive population. Drug-drug interactions (DDIs) from concomitant use of multiple drugs increase the risk of drug toxicities, sub-optimal therapy, and drug resistance. With the increase in polypharmacy, involving antiretroviral (ARV), and anticancer drugs, there is a greater need for an appreciation of clinically relevant DDIs. Anticancer and ARV drugs studied in this review were from The World Health Organization's Model List of Essential Medicines 2017. We reviewed; drug package inserts, www.drugbank.ca and www.UpToDate.com, to evaluate pharmacokinetic interactions with cytochrome P450 (CYP450) and ABCB1. The DDIs between drugs were assessed using the University Of Liverpool, UK HIV Drug Interactions Checker, and the LexiComp Drug Interaction tool of www.UpToDate.com. About 70% of ARVs studied interact with CYP450, all involve CYP3A4, and 55% interact with ABCB1. About 65% of anticancer drugs interact with CYP450, 44% of which do so through CYP3A4. About 75% of anticancer drugs interact with ARV drugs, with nine absolute contraindications to concomitant therapy. There exist a substantial number of DDIs between ARV and anticancer drugs, primarily mediated through CYP450 enzymes. Dolutegravir based regimens offer the safest DDI profile for concurrent use with anticancer drugs. However, there are substantial gaps in our knowledge, and this study serves to highlight the need for additional research to better define these interactions and their effect on drug exposure, as attention to these DDIs is a relatively simple intervention that could lead to optimizing disease treatment.

Drug-drug interactions with candidate medications used for COVID-19 treatment: An overview.

Drug‐drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID‐19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT‐prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID‐19 in order to minimize the adverse reactions.

Review of Statistical Methodologies for Detecting Drug-Drug Interactions Using Spontaneous Reporting Systems.

Concomitant use of multiple drugs for therapeutic purposes is known as “polypharmacy situations,” which has been recognized as an important social problem recently. In polypharmacy situations, each drug not only induces adverse events (AEs) but also increases the risk of AEs due to drug–drug interactions (DDIs). The proportion of AEs caused by DDIs is estimated to be around 30% of unexpected AEs. The randomized clinical trials in pre-marketing typically focus emphasis on the verification of single drug safety and efficacy rather than the surveys of DDI, and therefore, patients on multiple drugs are usually excluded. However, unlike pre-marketing randomized clinical trials, in clinical practice (= post marketing), many patients use multiple drugs. The spontaneous reporting system is one of the significant sources drug safety surveillance in post-marketing. Commonly, signals of potential drug-induced AEs detected from this source are validated in real-world settings. Recently, not only methodological studies on signal detection of “single” drug, but also on several methodological studies on signal detection of DDIs have been conducted. On the other hand, there are few articles that systematically summarize the statistical methodology for signal detection of DDIs. Therefore, this article reviews the studies on the latest statistical methodologies from classical methodologies for signal detection of DDIs using spontaneous reporting system. This article describes how to calculate for each detection method and the major findings from the published literatures about DDIs. Finally, this article presented several limitations related to the currently used methodologies for signal detection of DDIs and suggestions for further studies.

Potential drug-drug interactions in inpatients treated at the Internal Medicine ward of Tikur Anbessa Specialized Hospital.

PurposeAlthough the concomitant use of multiple drugs often increases therapeutic effectiveness, certain combinations result in unwanted drug–drug interactions (DDIs). Most interactions go unnoticed by physicians due to the absence of new clinical signs and symptoms, and because they often produce a worsening of already existing symptoms. Quantification of the occurrence of the potential DDIs is essential to prevent the harmful effects associated with interactions. This study was launched to assess the prevalence of potential DDIs in the Internal Medicine ward of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.Patients and methodsCross-sectional data were gathered from the medical charts of 252 randomly selected patients who were admitted to the Internal Medicine ward during August 23 to October 23, 2013, and exposed to at least two concomitant drugs. Potential DDIs were identified using Medscape Drug Interaction Checker. The data were analyzed using SPSS software. Logistic regression analysis was used to determine the presence of association between variables and p-value <0.05 was considered statistically significant.ResultsAt least one potential DDI was found in 78.2% of the patients. The mean number of potential interactions per patient was 3.7±3.4. Out of the 719 potential interactions identified, 49.8% were pharmacokinetic type, 44.6% were pharmacodynamic and the remaining 5.6% were unknown mechanisms. Major potential DDIs accounted for 13.1% of the whole interactions; 53.5% were moderate interactions; and the remaining 33.4% were minor interactions. Ceftriaxone, cimetidine and heparin were the three most involved drugs in major potential interactions. Prescription of five or more concomitant drugs was associated with high risk of encountering potential DDIs.ConclusionThe findings of this study showed that the prevalence of potential DDIs among inpatients was high. Pharmacists should closely review drugs prescribed for patients and avoid dispensing combinations of drugs that may have serious DDIs.

A study of harmful drug-drug interactions due to polypharmacy in hospitalized patients in Goa Medical College.

Introduction:Concomitant use of multiple drugs is often indicated to manage comorbid conditions and enhance efficacy. Such concomitant use of multiple drugs (five or more drugs) has been defined as “polypharmacy.” Polypharmacy has been associated with adverse consequences such as greater healthcare costs, increased risk of adverse drug events, drug–drug interactions (DDIs), medication nonadherence, reduced functional capacity, and multiple geriatric syndromes. This study evaluated number of potential harmful DDIs due to polypharmacy.Materials and Methods:A prospective, cross-sectional, observational study was performed from July 2011 to June 2012. Approval was obtained from the Institutional Ethics Committee, Goa Medical College. Drug interactions were identified using a computerized DDI database system Lexi-Comp version: 2.4.1. Quantitative data analysis was done by the SPSS for Windows version 17.0.Results:Seven hundred and fifty-one out of 5424 (13.85%) prescriptions were observed to have polypharmacy with highest rates observed in the Department of Medicine. The median age of patients was 55.60 ± 13.86 (range 10–108 years). A total number of drugs per prescription ranged from minimum of 5 to maximum of 16 drugs, with an average of 7.96 ± 1.75. A large number of 596 prescriptions contained 6–9 drugs per prescription. Drugs involved in potential DDIs in our study included aspirin, antacids, beta-blockers, 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, calcium channel blockers, angiotensin-converting enzyme inhibitors, ondansetron, and H2 blockers.Conclusion:Patients taking multiple medications experience unique pharmacotherapy. Personalized drug prescribing strategies and close monitoring of patients taking drugs with potential DDIs are keys to optimal therapeutic result.

Drug dispensings among elderly in the year before colon cancer diagnosis versus matched cancer-free controls.

The concomitant use of multiple drugs is common among the general population of elderly. The aim of this study was to provide an overview of which drugs are dispensed to elderly in the year before colon cancer diagnosis and to compare this with cancer-free controls. Data from the Eindhoven Cancer Registry were linked to the PHARMO Database Network. Patients with colon cancer aged ≥70years were included and matched with controls on gender, year of birth and postal code. Proportions of cases and controls with ≥1 dispensing of each WHO ATC-2-level drug during the total year and during each quarter of the year were calculated and differences between cases and controls tested. Proportion of cases with ≥1 drug dispensing was highest for drugs for constipation (cases vs. controls 58% vs. 10%), antithrombotics (42% vs. 33%), drugs for acid-related disorders (35% vs. 22%), antibacterials (34% vs. 24%), agents acting on the renin-angiotensin system (33% vs. 27%), beta-blockers (33% vs. 23%), lipid-modifying agents (29% vs. 22%), diuretics (29% vs. 21%), psycholeptics (25% vs. 18%) and antianaemics (23% vs. 6%). The proportion of cases with ≥1 drug dispensing increased from the first to the last quarter of the year for drugs for constipation (7%-53%), drugs for acid-related disorders (16%-27%), antibacterials (12%-16%), beta-blockers (26%-28%), psycholeptics (15%-19%) and antianaemics (6%-18%). Elevated proportions of cases with ≥1 drug dispensing for several drugs are mostly related to comorbidity, although increasing proportions of cases with ≥1 drug dispensing for certain drugs during the year can be attributed to the incidence of colon cancer. We have provided insight into which drugs are commonly used in the year preceding colon cancer diagnosis. This may trigger general practitioners and medical specialists to further evaluate the patient.

Factors that affect therapeutic efficacy and safety of drugs

According to the Law on medicines and medicinal devices, veterinary drugs must be of high quality, efficacy and safety to be suitable for use on animals. However, there are numerous factors which can alter the intensity of drugs and their established therapeutic efficacy and safety. These factors may depend on the patients themselves i.e. animals (species, age, sex, physiological state, impaired functions of organs involved in the elimination of drugs, diseases of other organ systems, nutrition, genetic disorders, individual variations, tolerance etc.), veterinary surgeons (use of the drug which is not in accordance with the instructions - ?off-label use?, improper selection of a drug or drug combination intended for a certain animal species or pathological condition, inadequate drug administration route, inadequate drug dosage and duration of therapy) and the drug itself (inappropriate formulation, bioavailability, instability of formulation, diminishing drug action due to external factors). Not following the instructions on using a drug and incorrect application may affect the rate and extent of the drug absorption. The route of the administration of a pharmaceutical product is defined in clinical trials, and depends on the physical and chemical properties of the active ingredient, characteristics of the pharmaceutical formulation and the anatomical and physiological characteristics of application sites which enable absorption. An adequate drug administration ensures a predictable level and rate of absorption from the application site, drug concentration at the sites of its action and pharmacological response or therapeutic efficacy. Concomitant use of multiple drugs in the same patient should be avoided because of possible interactions (antagonism or sinergism) which may decrease the activity of a drug and its effectiveness or increase them including appearance of drug toxicity. In addition, mixing drugs in an infusion system or a syringe should be avoided because the absence of visible interaction does not mean that the drugs applied are compatible.

Nancy Kishlar Mello.

Nancy Kishlar Mello.

Alcohol and ageing.

Older adults are sensitive to the effects of alcohol as a consequence of physiological changes associated with ageing, a high prevalence of diseases and concomitant use of multiple drugs. This study investigated the medicinal use of alcohol by individuals aged 65 years and over. The most commonly mentioned conditions were cardiovascular disease, sleep disturbances, common cold and indigestion. The amount taken was usually small but the authors say its use was associated with forgetting to take medicines, interactions with prescribed medicines and increased risks of falls and fractures. Older adults should be educated about alcohol consumption and use of medication.

Interpretation of Associations in Pharmacoepidemiology

Pharmacoepidemiology is an important tool for understanding and documenting the relationships between the use of drugs and adverse events. Side effects are an important consideration for clinicians making treatment decisions, and they also figure prominently in action by regulatory agencies. Unlike the results of randomized trials, epidemiologic findings are based on observational data subject to various types of bias; on the other hand, epidemiology has the advantage of monitoring "real world" situations. This chapter is intended to provide readers with a practical treatment of the issues that are encountered in the pharmacoepidemiology literature so that they can arrive at their own interpretation of the findings. The discussion is focused on issues that are of particular relevance to the epidemiologic study of drug associations with hematologic outcomes, including validity of exposure information, appropriate definition of exposure, confounding by indication and from concomitant use of multiple drugs, sample size considerations, and the relationship between size of an association and rarity of the outcome.

Potential drug interactions during a three-decade study period: a cross-sectional study of a prescription register

The thesis aimed to study the developments, in the area of pharmacoinformatics, of the electronic prescribing and dispensing processes of drugs - in medical praxis, follow-up, and research. For hundreds of years, the written prescription has been the method of choice for physicians to communicate decisions on drug therapy and for pharmacists to dispense medication. Successively the prescription has also become a source of information for the patient about how to use the medication to maximize its benefit. Currently, the medical prescription is at a transitional stage between paper and web, and to adapt a traditional process to the new electronic era offers both opportunities and challenges The studies in the thesis have shown that the exposure of prescribed drugs in the general population has increased considerably over three decades. The risk of receiving potentially interacting drugs was also strongly correlated to the concomitant use of multiple drugs, polypharmacy. The pronounced increase in polypharmacy over time constitutes a growing reason for prescribers and pharmacists to be aware of drug interactions. Still, there were relatively few severe potential drug interactions. Recently established national prescription registers should be evaluated for drug interaction vigilance, both clinically and epidemiologically. The Swedish National Pharmacy Register provides prescription dispensing information for the majority of the population. The medication history in the register may be accessed online to improve drug utilization, by registered individuals, prescribers, and pharmacists in a safe and secure way. Lack of widespread secure digital signatures in healthcare may delay general availability. With a relatively high prevalence of dispensed drugs in the population, the National Pharmacy Register seems justified in evaluating individual medication history. With a majority of prescriptions transferred as ePrescriptions, the detected increased risk for prescription errors warrants quality improvement, if the full potential of ePrescriptions is to be fulfilled. The main conclusion of the studies was that ePrescribing with communication of prescribed drug information, storing and retrieving dispensed drug information, offers new opportunities for clinical and scientific

Potential drug interactions during a three-decade study period: a cross-sectional study of a prescription register

The increased risk of adverse events in patients receiving potentially interacting drugs has long been recognized. The purpose of the present study was to evaluate the change in the risk of receiving potentially interacting drugs during a period covering three decades and to examine the relative risk of actual drug combinations. The prescriptions from all individuals (about 8,000) with two or more prescriptions during three periods of 15 months, October to December 1983-1984, 1993-1994 and 2003-2004, were collected from an ongoing cohort study in the county of Jämtland, Sweden. The potential interactions were detected by a computerized system. The relative risk (RR) of receiving potentially interacting drugs increased for type C interactions [RR: 1.177, 95% confidence interval (CI): 1.104-1.256] and decreased for type D interactions (RR: 0.714, 95% CI: 0.587-0.868) from the period 1983-1984 to 2003-2004. Polypharmacy for the participants increased by 61%, from 9.05 filled prescriptions per subject in 1983-1984 to 10.6 in 1993-1994 and 14.6 in 2003-2004. The RR was positively correlated to the pronounced increase in polypharmacy; in addition, an exponential relationship was found for the more severe type D interactions. Few interacting drug combinations were responsible for a large proportion of the risk. We conclude that the risk of receiving potentially interacting drugs was strongly correlated to the concomitant use of multiple drugs. The pronounced increase in polypharmacy over time implies a growing reason for prescribers and pharmacists to be aware of drug interactions. Recently established national prescription registers should be evaluated for drug interaction vigilance, both clinically and epidemiologically.