Drug Interactions

Polypharmacy, specifically the overuse and misuse of medications, is associated with adverse health events, increased disability, hospitalizations, and mortality. Mechanisms through which polypharmacy may increase adverse health outcomes include decreased adherence, increased drug side effects, higher use of potentially inappropriate medications, and more frequent drug-drug interactions. This article reviews clinical problems associated with polypharmacy and presents a framework to optimize prescribing for older adults...

BACKGROUND: Adverse drug reactions are one of the most common causes of death in industrialized Western countries. Nowadays, empirical data from clinical studies for the approval and monitoring of drugs and molecular databases is available. METHODS: The integration of database information is a promising method for providing well-based knowledge to avoid adverse drug reactions. This paper presents our web-based decision support system GraphSAW which analyzes and evaluates drug interactions and side effects based on data from two commercial and two freely available molecular databases...

IMPORTANCE: Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. OBJECTIVE: To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington...

BACKGROUND: With increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in patients undergoing hip and knee arthroplasty, some have advocated a dual-antibiotic regimen including vancomycin as prophylaxis against surgical site infections. However, routine administration of vancomycin may result in impaired renal functions in susceptible patients. QUESTIONS/PURPOSES: The purpose of this study was to determine whether patients receiving antibiotic prophylaxis with cefazolin and vancomycin have a higher risk of postoperative acute kidney injury (AKI) compared with patients receiving cefazolin alone before elective primary hip and knee arthroplasty...

BACKGROUND AND OBJECTIVES: Hospitalized infants, children, and adolescents are typically exposed to numerous distinct medications during inpatient admissions, increasing their risk of potential drug-drug interactions (PDDIs). We assessed the prevalence and characteristics of PDDI exposure of pediatric patients treated in children's hospitals. METHODS: This retrospective cohort study included patients <21 years old hospitalized in children's hospitals throughout the United States...

IMPORTANCE: Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia. OBJECTIVE: To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012...

BACKGROUND: Patients with chronic diseases often receive multiple medications and are associated with increased vulnerability to medication errors. Identifying high-alert medications for them would help to prioritize the interventions with greatest impact for improving medication safety. The aim of this study was to develop a list of high-alert medications for patients with chronic illnesses (HAMC list) that would prove useful to the Spanish National Health Service strategies on chronicity...

IMPORTANCE: Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia. OBJECTIVE: To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population...

UNLABELLED: Drug interactions may represent an iatrogenic risk that should be controlled in community pharmacies at the dispensing level. AIM: We analyzed the association between potential drug-drug interactions (DDIs) and negative clinical outcomes. METHODS: WE USED DISPENSING DATA FROM TWO COMMUNITY PHARMACIES: instances where drug dispensing was associated with a potential DDI and a comparison group of randomized dispensing operations with no potential DDI...

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them. AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies. EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone...

IMPORTANCE: Calcium-channel blockers are metabolized by the cytochrome P450 3A4 (CYP3A4; EC 1.14.13.97) enzyme. Blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4 and azithromycin is not, which makes comparisons between these 2 macrolide antibiotics useful in assessing clinically important drug interactions. OBJECTIVE: To characterize the risk of acute adverse events following coprescription of clarithromycin compared with azithromycin in older adults taking a calcium-channel blocker...

Characterizing interactions between drugs is important to avoid potentially harmful combinations, to reduce off-target effects of treatments and to fight antibiotic resistant pathogens, among others. Here we present a network inference algorithm to predict uncharacterized drug-drug interactions. Our algorithm takes, as its only input, sets of previously reported interactions, and does not require any pharmacological or biochemical information about the drugs, their targets or their mechanisms of action. Because the models we use are abstract, our approach can deal with adverse interactions, synergistic/antagonistic/suppressing interactions, or any other type of drug interaction...

BACKGROUND: Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4. OBJECTIVE: To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 2003 to 2010. PATIENTS: Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478)...

Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs. They are localized in organs such as small intestine, liver, and kidney, which are critical for drug absorption and elimination. Moreover, they can be found in important blood-tissue barriers such as the blood-brain barrier. Inhibition or induction of drug transporters by coadministered drugs can alter pharmacokinetics and pharmacodynamics of the victim drugs. This review will summarize in particular clinically observed drug-drug interactions attributable to inhibition or induction of intestinal export transporters [P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)], to inhibition of hepatic uptake transporters [organic anion transporting polypeptides (OATPs)], or to inhibition of transporter-mediated [organic anion transporters (OATs), organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), P-gp] renal secretion of xenobiotics...

Drug-drug interactions (DDIs) are an emerging threat to public health. Recent estimates indicate that DDIs cause nearly 74000 emergency room visits and 195000 hospitalizations each year in the USA. Current approaches to DDI discovery, which include Phase IV clinical trials and post-marketing surveillance, are insufficient for detecting many DDIs and do not alert the public to potentially dangerous DDIs before a drug enters the market. Recent work has applied state-of-the-art computational and statistical methods to the problem of DDIs...

The use of complementary and alternative medicines (CAM) by cancer patients is increasing. Concomitant use of CAM and anticancer drugs could lead to serious safety issues in patients. CAM have the potential to cause pharmacokinetic interactions with anticancer drugs, leading to either increased or decreased plasma levels of anticancer drugs. This could result in unexpected toxicities or a reduced efficacy. Significant pharmacokinetic interactions have already been shown between St. John's Wort (SJW) and the anticancer drugs imatinib and irinotecan...

Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes...

BACKGROUND: Drug-drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs. METHODS: We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs...

This MiniReview is a personal recollection of selected research topics, which the author in collaboration with colleagues has studied, aiming to improve the predictability of drug therapy. In early studies, we found bi- and trivalent cations to reduce the absorption of various tetracyclines and fluoroquinolones. Certain antacids elevated the bioavailability of some non-steroidal anti-inflammatory drugs and sulphonylureas. Various brands of phenytoin tablets revealed great differences in their bioavailability, causing clinical consequences...

After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone...