Drug Interaction Database Research Articles

A Modified Skip-Gram Algorithm for Extracting Drug-Drug Interactions from AERS Reports.

Drug-drug interactions (DDIs) are one of the indispensable factors leading to adverse event reactions. Considering the unique structure of AERS (Food and Drug Administration Adverse Event Reporting System (FDA AERS)) reports, we changed the scope of the window value in the original skip-gram algorithm, then propose a language concept representation model and extract features of drug name and reaction information from large-scale AERS reports. The validation of our scheme was tested and verified by comparing with vectors originated from the cooccurrence matrix in tenfold cross-validation. In the verification of description enrichment of the DrugBank DDI database, accuracy was calculated for measurement. The average area under the receiver operating characteristic curve of logistic regression classifiers based on the proposed language model is 6% higher than that of the cooccurrence matrix. At the same time, the average accuracy in five severe adverse event classes is 88%. These results indicate that our language model can be useful for extracting drug and reaction features from large-scale AERS reports.

A Collaborative Medication Review Including Deprescribing for Older Patients in an Emergency Department: A Longitudinal Feasibility Study.

Medication review for older patients with polypharmacy in the emergency department (ED) is crucial to prevent inappropriate prescribing. Our objective was to assess the feasibility of a collaborative medication review in older medical patients (≥65 years) using polypharmacy (≥5 long-term medications). A pharmacist performed the medication review using the tools: Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, a drug–drug interaction database (SFINX), and Renbase® (renal dosing database). A geriatrician received the medication review and decided which recommendations should be implemented. The outcomes were: differences in Medication Appropriateness Index (MAI) and Assessment of Underutilization Index (AOU) scores between admission and 30 days after discharge and the percentage of patients for which the intervention was completed before discharge. Sixty patients were included from the ED, the intervention was completed before discharge for 50 patients (83%), and 39 (61.5% male; median age 80 years) completed the follow-up 30 days after discharge. The median MAI score decreased from 14 (IQR 8-20) at admission to 8 (IQR 2-13) 30 days after discharge (p < 0.001). The number of patients with an AOU score ≥1 was reduced from 36% to 10% (p < 0.001). Thirty days after discharge, 83% of the changes were sustained and for 28 patients (72%), 1≥ medication had been deprescribed. In conclusion, a collaborative medication review and deprescribing intervention is feasible to perform in the ED.

Placental transporter-mediated drug interactions and offspring congenital anomalies.

AimsP‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) are efflux transporters expressed in the placenta, limiting their substrates from reaching the foetus. Our aim was to investigate if concomitant prenatal exposure to several substrates or inhibitors of these transporters increases the risk of congenital anomalies.MethodsThe national Drugs and Pregnancy database, years 1996–2014, was utilized in this population‐based birth cohort study. In the database, the Medical Birth Register, the Register on Induced Abortions, the Malformation register and the Register on Reimbursed Drug Purchases have been linked. The University of Washington Metabolism and Transport Drug Interaction Database was used to identify substrates and inhibitors of P‐gp and BCRP. We included singleton pregnancies ending in birth or elective termination of pregnancy due to foetal anomaly. Known teratogens were excluded. We identified women exposed 1 month before pregnancy or during the first trimester to P‐gp/BCRP polytherapy (n = 21 186); P‐gp/breast cancer resistance protein monotherapy (n = 97 906); non‐P‐gp/BCRP polytherapy (n = 78 636); and unexposed (n = 728 870). We investigated the association between the exposure groups and major congenital anomalies using logistic regression adjusting for several confounders.ResultsThe prevalence of congenital anomalies was higher in the P‐gp/BCRP polytherapy group (5.5%) compared to the P‐gp/BCRP monotherapy (4.7%, OR 1.13; 95% CI 1.05–1.21), the non‐P‐gp/BCRP polytherapy (4.9%, OR 1.14; 95% CI 1.06–1.22), and to the unexposed groups (4.2%, OR 1.23; 95% CI 1.15–1.31).ConclusionThe results suggest a role of placental transporter‐mediated drug interactions in teratogenesis.

Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents.

As yet, no agents have been approved for the treatment of COVID-19, although several experimental drugs are being used off licence. These may have serious adverse effects and potential drug interactions with psychotropic agents. We reviewed the common agents being used across the world for the treatment of COVID-19 and investigated their drug interaction potential with psychotropic agents using several drug interaction databases and resources. A preliminary search identified the following drugs as being used to treat COVID-19 symptoms: atazanavir (ATV), azithromycin (AZI), chloroquine (CLQ)/hydroxychloroquine (HCLQ), dipyridamole, famotidine (FAM), favipiravir, lopinavir/ritonavir (LPV/r), nitazoxanide, remdesivir, ribavirin and tocilizumab. Many serious adverse effects and potential drug interactions with psychotropic agents were identified. The most problematic agents were found to be ATV, AZI, CLQ, HCLQ, FAM and LPV/r in terms of both pharmacokinetic as well as serious pharmacodynamic drug interactions, including QTc prolongation and neutropenia. Significant caution should be exercised if using any of the medications being trialled for the treatment of COVID-19 until robust clinical trial data are available. An even higher threshold of vigilance should be maintained for patients with pre-existing conditions and older adults due to added toxicity and drug interactions, especially with psychotropic agents.

Drug-Drug Interactions of 257 Antineoplastic and Supportive Care Agents With 7 Anticoagulants: A Comprehensive Review of Interactions and Mechanisms.

Data on drug–drug interactions (DDI) of antineoplastic drugs with anticoagulants is scarce. We aim to evaluate factors associated with DDI of antineoplastic and supportive care drugs with anticoagulants resulting in modification of pharmacokinetics of these last mentioned. A literature review on DDI databases and summaries of products characteristics (SmPC) was done. Drug–drug interactions of 257 antineoplastic and supportive care drugs with direct oral anticoagulants (DOACs), warfarin, enoxaparin, or fondaparinux were categorized as no clinically significant expected DDI, potentially weak DDI, potentially clinically significant DDI, and recommendation against coadministration. Logistic regression models were performed to analyze the association between the dependent variable potentially clinically significant interaction/recommendation against coadministration and the mechanisms of DDI. Of the 1799 associations, 84.4% were absence of DDI, 3.6% potentially weak DDI, 10.2% potentially clinically relevant DDI, and 2.0% recommendation against coadministration. Warfarin has higher DDI potential than other anticoagulants. Enoxaparin and fondaparinux have fewer DDI than others. There was no difference between DOACs. Drug–drug interactions with apixaban and rivaroxaban was independently associated with the absence of CYP3A4 competition, P-glycoprotein inhibition, CYP3A4 induction, and drug class of tyrosine kinase inhibitors. Drug–drug interactions with dabigatran and edoxaban was associated with inhibition of P-glycoprotein and tyrosine kinase inhibitors. Warfarin, induction of CYP3A4, and inhibition of CYP2C9. Enoxaparin and fondaparinux, only tyrosine kinase inhibitors. Direct oral anticoagulants did not differ regarding DDI with antineoplastic agents. Warfarin presented more DDI than other anticoagulants. P-glycoprotein inhibition and CYP3A4 induction were independently associated with DDI of antineoplastic agents with DOACs.

Pharmacists should make themselves familiar with the Antifungal Drug Interactions Database

Pharmacists should make themselves familiar with the Antifungal Drug Interactions Database

„Human-immunodeficiency-virus“-Infektion im Alter

Due to the excellent efficacy of antiretroviral treatment increasingly more people with human immunodeficiency virus (HIV) infections survive to old age. The national and international definition of older people with HIV infections comprises those aged 50 years and older. Practitioners caring for these patients have to take age-related comorbidities and polypharmacy into account. Cooperation between HIV caregivers and general practitioners as well as geriatric specialists should provide anetwork that covers topics such as vaccinations, early detection of malignancies and psychosocial aspects, such as loneliness and organization of nursing care. Aschedule for preventive measures is presented in this article as well as practical approaches including access to drug interaction databases and HIV treatment guidelines.

Real-world prevalence of potential drug-drug interactions involving oral antineoplastic agents: a population-based study.

We aimed to gain insight into the real-world prevalence of potentially significant drug-drug interactions (DDIs) involving oral antineoplastic agents using nationwide data in Korea. The data from the 2016 and 2017 Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) of South Korea were used. The drugs prescribed concomitantly with oral anticancer drugs were screened for the potential DDIs by using two international DDI databases: LexicompTM and Micromedex®. Potentially significant DDIs were defined as DDIs with a severity rating of "major" or higher from at least one reference. The DDIs were classified into category 1 if the severity ratings were major or higher using both references. Overall 5657 cases of DDIs in 2925 patients (26.4%) and 1640 cases of category 1 DDIs in 997 patients (9.0%) were identified among 11,076 patients receiving oral anticancer drugs. The prevalence was highest among the targeted agents (63.2%) followed by traditional (21.2%) and endocrine agents (19.3%). The common potential clinical consequences were increased risk of corrected QT interval prolongation (36.7%), reduced efficacy of antineoplastic agents (30.4%), and increased toxicities of antineoplastic agents (8.0%). Polypharmacy and the duration of oral cancer treatment increased the likelihood of potential DDIs in addition to individual antineoplastic agents. This study showed that potentially significant DDIs with oral antineoplastic agents were prevalent in real-world practice. Recognizing the high prevalence of DDIs among patients taking oral antineoplastic agents is a necessary step toward improving the clinical outcome.

A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug-Drug Interactions with Orally Administered Medications.

Background and ObjectiveSeveral review articles have been published discussing gastric acid-related drug–drug interactions (DDIs) mediated by coadministration of antacids, histamine H2 receptor antagonists, or proton pump inhibitors, but are not sufficiently comprehensive in capturing all documented DDIs with acid-reducing agents (ARAs) and tend to focus on gastric pH-dependent DDIs and/or basic drugs. Subsequently, several new drugs have been approved, and new information is available in the literature. The objective of this systematic review is to comprehensively identify oral medications that have clinically meaningful DDIs, including loss of efficacy or adverse effects, with gastric ARAs, and categorize these medications according to mechanism of interaction.MethodsAn indepth search of clinical data in the PDR3D: Reed Tech Navigator™ for Drug Labels, University of Washington Drug–Drug Interaction Database, DailyMed, Drugs@FDA.gov, and UpToDate®/Lexicomp® Drug and Drug Interaction screening tool was conducted from 1 June to 1 August 2018. The PDR3D, University of Washington Drug–Drug Interaction Database, and DailyMed were searched with terms associated with gastric acid and ARAs. Conflicting findings were further investigated using the UpToDate®/Lexicomp® screening tool. Clinical relevance was assessed on whether an intervention was needed, and prescribing information and/or literature supporting the DDI.ResultsThrough the search strategy, 121 medications were found to clinically meaningfully interact with ARAs. For 38 medications the mechanism of interaction with ARAs was identified as gastric pH dependent, and for 83 medications the interaction was found to be not gastric pH mediated, with mechanisms involving metabolic enzymes, transporters, chelation, and urine alkalization. Additionally, 109 medications were studied and did not have a clinically meaningful interaction with ARAs.ConclusionThis review may provide a resource to healthcare professionals in aiding the care of patients by increasing awareness of interactions with ARAs and may also identify and potentially aid in avoiding clinically relevant DDIs and preventing risk of treatment failure and/or adverse effects. Advances in non-clinical predictions of gastric pH-mediated DDIs may guide the need for a future clinical evaluation.Electronic supplementary materialThe online version of this article (10.1007/s40262-019-00844-3) contains supplementary material, which is available to authorized users.

A Cross-Sectional Study on Single-Day Use of Proton Pump Inhibitors in Tertiary Care Hospitals of South India.

Background: Proton pump inhibitors (PPIs) are the most potent antacids used in clinical practice with greater safety and efficacy. Limited data are available on the usage of PPIs in Indian health-care settings. Our aim was to understand the usage pattern and potential drug interactions with concurrently administered medications employing a single-day cross-sectional study design. Methods: A prospective observational cross-sectional study conducted on a single day, at two tertiary care teaching hospitals in South India. Inpatients of above 18 years of age were included. Case profiles were reviewed and data were collected in predesigned forms and analyzed. Drug interactions were identified using Micromedex and Medscape drug-interaction databases. Results: A total of 797 case profiles screened from both the centers; 714 were prescribed with PPIs. In intensive care units (ICUs), the use of PPIs was highest with 95% of cases getting these drugs. A PPI was seen in about 93% of patients, who had more than or equal to 4 drugs in their prescriptions. Pantoprazole was the mostly prescribed PPI in around 90% of the cases. Around 33% of the PPIs usage was through IV (intravenous) route, and 75% of that use was seen in wards. Around 134 drug interactions were identified, of which 10 were of major severity. Conclusions: Around 90% of inpatients were prescribed with PPIs. Pantoprazole is the most commonly prescribed PPI (90%). The IV administration was seen more in wards than ICUs, and 10 major drug interactions were observed in this single-day study. Careful monitoring is needed to avoid serious drug interactions involving PPIs, and training programs should sensitize the clinicians on the evidence-based use of PPIs.

Clinical Controversy in Transplantation: Tacrolimus Versus Cyclosporine in Statin Drug Interactions.

Objective: To review the available literature that provides evidence for the absence of statin interactions with tacrolimus compared with cyclosporine. Data Sources: A literature search of PubMed was performed (1990 to June 2019) using the following search terms: calcineurin inhibitors, tacrolimus, cyclosporine, statins, atorvastatin, simvastatin, and drug interactions. Clinical practice guidelines, article bibliographies, drug interaction database references, and product monographs were also reviewed. Study Selection and Data Extraction: Relevant English-language studies describing the mechanism of interaction, the magnitude of pharmacokinetic alterations, and safety were evaluated. In vitro data and studies conducted in adult humans were considered. Data Synthesis: Studies demonstrate pharmacokinetic differences between cyclosporine and tacrolimus, particularly with regard to inhibition of 2 hepatic transporters: P-glycoprotein and organic anion transporting polypeptide (OATP). Compared with cyclosporine, tacrolimus does not affect these transporters, does not enhance statin exposure, and does not increase statin-associated safety events. Relevance to Patient Care and Clinical Practice: Clinical practice guidelines allude to the need to reduce statin doses in the setting of tacrolimus. Some providers have adopted this practice, and doing so may prevent transplant recipients from attaining cardiovascular benefit, especially when increased or high-intensity doses are required. The pharmacokinetic differences between tacrolimus and cyclosporine highlight different interaction potential with statins. Conclusions: Clinicians need to be aware that tacrolimus and cyclosporine are not the same with regard to causing drug interactions with statins. Tacrolimus can be used with statins without the need for dose adjustments because of lack of an interaction.

Prevalence of potential drug-drug interactions in Swedish pediatric outpatients.

PurposeTo describe the occurrence of potential drug-drug interactions (DDIs) in prescribed drugs, dispensed to pediatric outpatients in Sweden.MethodsA cross sectional study was conducted based on data from a national register of prescribed drugs, dispensed at pharmacies, to children 0–17 years old. The study period was January 1 to April 30, 2010. Drug dispensing data was linked to the DDI database SFINX. Prevalence and frequencies of potential interactions were investigated, and drugs commonly involved in interactions were identified. The study focused on clinically relevant potential interactions, class D (should be avoided), and class C (can be handled, e.g. by dose adjustment).ResultsIn the Swedish pediatric population, 0 to 17 years of age, 12% (n = 231 078) of children had at least two dispensed drugs. In this group of patients, 0.14% had potential D-interactions and 1,3% had potential C-interactions. The number of D- and C-interactions that may lead to reduced effects were 181 (52%), and 1224 (32%) respectively. The ten most frequent drugs were involved in 78% and 65% of all potential D-, and C-interactions respectively. Furthermore, 80%, and 58% of the D-, and C-interactions respectively occurred in patients aged 12 to 17.ConclusionsWe identified a limited number of drugs that were represented in the majority of potential interactions. Interactions that can lead to a reduced treatment effect constituted approximately half of D-interactions, and a third of C-interactions. The frequency of potential interactions was higher in older children. The results may contribute to increased prescriber awareness of important potential drug interactions among pediatric outpatients.

The Incidence and Severity of Drug Interactions Before and After Antiretroviral Therapy Simplification in Treatment-Experienced Patients With HIV Infection.

Background: Current guidelines advocate for antiretroviral therapy (ART) simplification in patients on complicated regimens. Simplifying ART improves patient adherence and quality of life, but changes in drug interactions (DIs) are uncertain. Objective: This study assessed changes in DIs following ART simplification in patients with HIV. Methods: This was an observational, retrospective cohort study of patients attending an urban HIV clinic. Patients were included if they had ART simplification (a decreased number of daily tablets) and ≥1 concomitant medication (CM). Total DI scores were generated for each patient pre-ART simplification and post-ART simplification using an online DI database. Each ART-CM pair labeled as "do not co-administer" was given a score of 2, "potential interaction" a score of 1, or "no interaction" a score of 0. Differences in total DI scores following simplification were analyzed with a Wilcoxon Signed-Rank test. Predictors of DI score reductions were examined with linear regression. Results: A total of 99 patients were included. Their median age was 54 years, and 79% were male. The median durations of HIV infection and ART were 16 and 10 years, respectively. Patients were receiving an average of 4.5 CMs. Median interaction scores presimplification and postsimplification were 3 (interquartile range [IQR], 1-6) and 1 (IQR, 0-2) respectively (P < 0.001). Predictors of score reductions were the patient's number of CMs, discontinuing a protease inhibitor, and switching to a dolutegravir-based regimen. Conclusion and Relevance: ART simplification decreased the incidence of DIs in this analysis of patients with advanced age who had ART experience and polypharmacy.

Drug-Drug Interaction Checker

Drugs are chemical substances intended for use in the cure, treatment, or prevention of diseases. When different drugs are taken together, a drug-drug interaction can delay, decrease, or enhance absorption of either drug and may cause adverse effects. Therefore, a system that allows the user to easily check drug-drug interaction has been designed. The drug-drug interaction database is integrated into decision support systems to be used in hospitals and pharmacies for clinical evaluation of interactions. The database has been created by using Microsoft Excel sheet that involves 3 sheets representing groups, drugs, and interactions, respectively. The processing of data has been implemented using artificial neural network (nntool). The accuracy and sensitivity were tested by using neural network and found to be 100%. Finally the graphical user interface was implemented to help the user to interface with the system.

Guidance for Rifampin and Midazolam Dosing Protocols To Study Intestinal and Hepatic Cytochrome P450 (CYP) 3A4 Induction and De-induction.

Cytochrome P450 3A4 (CYP3A4) catalyses the metabolism of > 30% of clinically used small molecule drugs. Induction of CYP3A4 is often associated with clinically important metabolic drug-drug interactions (DDIs). To collate published data regarding induction of CYP3A4 expression by rifampin and identify an optimal protocol to study DDIs using physiologically based pharmacokinetic (PBPK) modelling. The University of Washington Drug Interaction Database was searched for published data regarding induction of CYP3A4 by rifampin. A verified PBPK model was used to define the optimal dose, duration, timing and route of administration of rifampin and midazolam to assess induction of intestinal and hepatic CYP3A4 by rifampin. Sensitivity analysis was performed to evaluate the impact of participant characteristics including sex, race and age. The maximal induction of intestinal CYP3A4 (9.5-fold) was almost double that of hepatic CYP3A4 (5.5-fold). Maximal induction of intestinal and hepatic CYP3A4 was achieved in > 90% of participants within 5 and 10days, respectively. Intestinal CYP3A4 expression returned to baseline in > 90% of participants within 7days of rifampin cessation, whereas induction of hepatic CYP3A4 persisted for greater than 7days in > 50% of participants. There was a significant difference in magnitude, but not time course, of CYP3A4 induction between males and females. Age and race did not significantly affect either the magnitude or time course of CYP3A4 induction. Maximal induction of intestinal CYP3A4 is achieved faster than hepatic CYP3A4. To assess maximal hepatic CYP3A4 induction, oral rifampin (600mg daily) should be dosed for > 10days.

Physicochemical Properties, Biotransformation, and Transport Pathways of Established and Newly Approved Medications: A Systematic Review of the Top 200 Most Prescribed Drugs vs. the FDA-Approved Drugs Between 2005 and 2016.

Enzyme-mediated biotransformation of pharmacological agents is a crucial step in xenobiotic detoxification and drug disposition. Herein, we investigated the metabolism and physicochemical properties of the top 200 most prescribed drugs (established) as well as drugs approved by the US Food and Drug Administration (FDA) between 2005 and 2016 (newly approved). Our objective was to capture the changing trends in the routes of administration, physicochemical properties, and prodrug medications, as well as the contributions of drug-metabolizing enzymes and transporters to drug clearance. The University of Washington Drug Interaction Database (DIDB®) as well as other online resources (e.g., CenterWatch.com, Drugs.com, DrugBank.ca, and PubChem.ncbi.nlm.nih.gov) was used to collect and stratify the dataset required for exploring the above-mentioned trends. Analyses revealed that ~ 90% of all drugs in the established and newly approved drug lists were administered systemically (oral or intravenous). Meanwhile, the portion of biologics (molecular weight > 1kDa) was 15 times greater in the newly approved list than established drugs. Additionally, there was a 4.5-fold increase in the number of compounds with a high calculated partition coefficient (cLogP>3) and a high total polar surface area (> 75Å2) in the newly approved drug vs. the established category. Further, prodrugs in established or newly approved lists were found to be converted to active compounds via hydrolysis, demethylases, and kinases. The contribution of cytochrome P450 (CYP) 3A4, as the major biotransformation pathway, has increased from 40% in the established drug list to 64% in the newly approved drug list. Moreover, the role of CYP1A2, CYP2C19, and CYP2D6 were decreased as major metabolizing enzymes among the newly approved medications. Among non-CYP major metabolizers, the contribution of alcohol dehydrogenases/aldehyde dehydrogenases (ADH/ALDH) and sulfotransferases decreased in the newly approved drugs compared with the established list. Furthermore, the highest contribution among uptake and efflux transporters was found for Organic Anion Transporting Polypeptide 1B1 (OATP1B1) and P-glycoprotein (P-gp), respectively. The higher portion of biologics in the newly approved drugs compared with the established list confirmed the growing demands for protein- and antibody-based therapies. Moreover, the larger number of hydrophilic drugs found in the newly approved list suggests that the probability of toxicity is likely to decrease. With regard to CYP-mediated major metabolism, CYP3A5 showed an increased involvement owing to the identification of unique probe substrates to differentiate CYP3As. Furthermore, the contribution of OATP1B1 and P-gp did not show a significant shift in the newly approved drugs as compared to the established list because of their broad substrate specificity.

A comparison of potential psychiatric drug interactions from six drug interaction database programs

Harmful drug-drug interactions (DDI) frequently include psychiatric drugs. Drug interaction database programs are viewed as a primary tool to alert physicians of potential DDI, but may provide different results as there is no standard to define DDI. This study compared the category of potential DDI provided by 6 commercial drug interaction database programs (3 subscription, 3 open access) for 100 drug interaction pairs. The pairs involved 94 different drugs; 67 included a psychiatric and non-psychiatric drug, and 33 included two psychiatric drugs. The category assigned to the potential DDI by the 6 programs was compared using percent agreement and Fleiss’ kappa interrater reliability measure. The overall percent agreement for the category of potential DDI for the 100 drug interaction pairs was 66%. The Fleiss kappa overall interrater agreement was fair. The kappa agreement was substantial for interaction pairs with any severe category rating, and fair for interaction pairs with any major category rating. The category of potential DDI for drug interaction pairs including psychiatric drugs often differs among drug interaction database programs. Modern technology allows easy access to several interaction database programs. When assistance from a drug interaction database program is needed, the physician should check more than one program.

Identification and Evaluation of Clinical Substrates of Organic Anion Transporting Polypeptides 1B1 and 1B3.

Organic anion transporting polypeptides (OATPs) 1B1 and 1B3 facilitate the uptake of drugs and endogenous compounds into the liver. In recent years, the impact of these transporters on drug–drug interactions (DDIs) has become a focus of research, and the evaluation of their role in drug disposition is recommended by regulatory agencies worldwide.1–3 Although sensitive substrates of OATP1B1/1B3 have been identified in the literature and probe drugs have been proposed by regulatory agencies, there is no general consensus on the ideal in vivo substrate for clinical DDI studies as analysis may be confounded by contribution from other metabolic and/or transport pathways.1–3 A thorough analysis of the available in vitro and in vivo data regarding OATP1B1/1B3 substrates was performed using the in vitro, clinical, and pharmacogenetic modules in the University of Washington Drug Interaction Database. A total of 34 compounds were identified and further investigated as possible clinical substrates using a novel indexing system. By analyzing the compounds for in vivo characteristics, including sensitivity to inhibition by known OATP1B1/1B3 inhibitors, selectivity for OATP1B1/1B3 compared with other transport and metabolic pathways, and safety profiles, a total of six compounds were identified as potential clinical markers of OATP1B1/1B3 activity.

Managing Pharmacotherapy in People Living With HIV and Concomitant Malignancy.

Objective: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. Data Sources: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. Study Selection and Data Extraction: Article bibliographies and drug interaction databases were reviewed. Search terms included HIV, antiretroviral therapy, antineoplastic agents, malignancies, and drug interactions. Data Synthesis: In the pre-antiretroviral therapy (ART) era, malignancies in PLWH were AIDS-defining illnesses, and life expectancy was shorter. Nowadays, PLWH are living longer and developing malignancies, including lung, anal, and prostate cancers. Concurrently, the oncology landscape has evolved, with novel oral targeted agents and immunotherapies becoming routine elements of care. The increased need for and complexity with antineoplastics in PLWH has led to recommendations for multidisciplinary care of this unique population. Evaluation of DDIs requires review of metabolic pathways, absorption mechanisms, and various drug transporters associated with antineoplastics and ART. Relevance to Patient Care and Clinical Practice: This review summarizes available data of non-AIDS-defining malignancies, principles of HIV care in the patient with malignancy, and guidance for assessing DDIs between antineoplastics and ART. Summary DDI tables provide point-of-care recommendations. Conclusions: The availability of ART has transformed AIDS into a chronic medical condition, and PLWH are experiencing age-related malignancies. Pharmacists play an important role in the management of this patient population.

Potential Interactions of Biologically Based Complementary Medicine in Gynecological Oncology.

Objective. The aim of this study was to assess the potential risks of interactions between biologically based complementary and alternative medication (BB-CAM) and conventional drugs during systemic therapy in breast and gynecological cancer patients by analyzing the actual CAM-drug combinations from individual patients’ records. Methods. From September 2014 to December 2014 and from February 2017 to May 2017, all patients (n = 717) undergoing systemic therapy at the Gynecologic Oncology Day Care Unit in the Gynecology and Obstetrics Department of the Technical University of Munich, Germany, were asked to participate in a questionnaire about all their medications. To assess the potential risk of CAM-drug interactions (CDIs), we initially utilized the Lexicomp drug interaction database. This assessment was then expanded with a systematic search of other digital databases, such as the National Center for Complementary and Integrative Health, Memorial Sloan Kettering Cancer Center, PubMed, and MEDLINE as well as the Cochrane Library. Results. Among 448 respondents, 74.1% reported using BB-CAM simultaneously with their systemic therapy. The assessment showed 1 patient with a potentially clinically relevant CDI, where the interaction was based on a self-medicated combination of Echinacea and cyclophosphamide. Furthermore, 81 patients (18.1%) were thought to have interactions because of a combination of BB-CAMs and cytochrome P450 3A4–metabolized anticancer drugs. Conclusions. Our data demonstrated high overall use of BB-CAMs by cancer patients undergoing systemic therapy. The analyses showed only 1 clinically relevant CDI.