Life-threatening Drug-drug Interactions Research Articles

Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management.

Colchicine is useful for the prevention and treatment of gout and a variety of other disorders. It is a substrate for CYP3A4 and P-glycoprotein (P-gp), and concomitant administration with CYP3A4/P-gp inhibitors can cause life-threatening drug-drug interactions (DDIs) such as pancytopenia, multiorgan failure, and cardiac arrhythmias. Colchicine can also cause myotoxicity, and coadministration with other myotoxic drugs may increase the risk of myopathy and rhabdomyolysis. Many sources of DDI information including journal publications, product labels, and online sources have errors or misleading statements regarding which drugs interact with colchicine, as well as suboptimal recommendations for managing the DDIs to minimize patient harm. Furthermore, assessment of the clinical importance of specific colchicine DDIs can vary dramatically from one source to another. In this paper we provide an evidence-based evaluation of which drugs can be expected to interact with colchicine, and which drugs have been stated to interact with colchicine but are unlikely to do so. Based on these evaluations we suggest management options for reducing the risk of potentially severe adverse outcomes from colchicine DDIs. The common recommendation to reduce the dose of colchicine when given with CYP3A4/P-gp inhibitors is likely to result in colchicine toxicity in some patients and therapeutic failure in others. A comprehensive evaluation of the almost 100 reported cases of colchicine DDIs is included in table form in the electronic supplementary material. Colchicine is a valuable drug, but improvements in the information about colchicine DDIs are needed in order to minimize the risk of serious adverse outcomes.

A Shared Decision-making Tool for Drug Interactions Between Warfarin and Nonsteroidal Anti-inflammatory Drugs: Design and Usability Study.

BackgroundExposure to life-threatening drug-drug interactions (DDIs) occurs despite the widespread use of clinical decision support. The DDI between warfarin and nonsteroidal anti-inflammatory drugs is common and potentially life-threatening. Patients can play a substantial role in preventing harm from DDIs; however, the current model for DDI decision-making is clinician centric.ObjectiveThis study aims to design and study the usability of DDInteract, a tool to support shared decision-making (SDM) between a patient and provider for the DDI between warfarin and nonsteroidal anti-inflammatory drugs.MethodsWe used an SDM framework and user-centered design methods to guide the design and usability of DDInteract—an SDM electronic health record app to prevent harm from clinically significant DDIs. The design involved iterative prototypes, qualitative feedback from stakeholders, and a heuristic evaluation. The usability evaluation included patients and clinicians. Patients participated in a simulated SDM discussion using clinical vignettes. Clinicians were asked to complete eight tasks using DDInteract and to assess the tool using a survey adapted from the System Usability Scale.ResultsThe designed DDInteract prototype includes the following features: a patient-specific risk profile, dynamic risk icon array, patient education section, and treatment decision tree. A total of 4 patients and 11 clinicians participated in the usability study. After an SDM session where patients and clinicians review the tool concurrently, patients generally favored pain treatments with less risk of gastrointestinal bleeding. Clinicians successfully completed the tasks with a mean of 144 (SD 74) seconds and rated the usability of DDInteract as 4.32 (SD 0.52) of 5.ConclusionsThis study expands the use of SDM to DDIs. The next steps are to determine if DDInteract can improve shared decision-making quality and to implement it across health systems using interoperable technology.

Evaluation of knowledge, attitude and practice of healthcare providers towards life-threatening drug-drug interactions in Penang General Hospital, Malaysia

IntroductionThe evaluation of knowledge, attitude, and practice (KAP) of health care providers on the life-threatening drug-drug interactions (DDIs) and the implementation of specific interventions may enhance patients’ safety. The current study was designed to evaluate the KAP of healthcare providers (HCPs) on life-threatening DDIs using different drug information sources. MethodsValidated questionnaire contains demographic data, knowledge and practice questions related to the life-threatening DDIs, and attitude towards the preferable sources of drug information. The survey forms were distributed to pharmacists as well as ward doctors in departments of cardiology, nephrology, neurology, and infectious diseases, in Penang General Hospital, Penang, Malaysia. ResultsThe overall response rate for 220 distributed questionnaires was 65.45%. Knowledge level is associated with healthcare specialty (p < 0.001), with 100% houseman officer having low knowledge, years of experience (p < 0.05) (50% of the HCPs with11–15 years of experience had high knowledge) and postgraduate study (p < 0.05), which 78.2% of HCPs without postgraduate studies had a low knowledge level. An association was obtained between knowledge level and attitude towards the use of computerized interaction checker (25% and 66.7% of respondents with high knowledge level had agreed and strongly agreed, respectively, to use computerized interaction checker, p < 0.05). Respondents with high knowledge level had agreed (33%) and strongly agreed (33%) to practice screening of DDIs at admission, p < 0.05. ConclusionPrescribers may have insufficient knowledge to avoid potential life-threatening DDIs. These findings affirm the necessity of well-designed computerized alerting systems, in addition to highlighting on pharmacists’ role as the competent source of drug information.

Drug Interactions With New Synthetic Opioids.

Fentanyl, fentanyl analogs, and other new synthetic opioids (NSO) have burst onto the illegal drug market as new psychoactive substances (NPS). They are often sold as heroin to unsuspecting users and produce euphoria through their agonist action on μ- opioid receptors. Their high consumption, often combined with other substances, has led to multiple intoxications during recent years. In some countries, such as the United States, the consumption of opioids, whether for medical or recreational purposes, has become epidemic and is considered a public health problem. Fentanyl analogs are more potent than fentanyl which in turn is 50 times more potent than morphine. Furthermore, some fentanyl analogs have longer duration of action and therefore interactions with other substances and medicines can be more serious. This review is focused on the potentially most frequent interactions of opioid NPS taking into account the drugs present in the reported cases of poly-intoxication, including other illegal drugs of abuse and medication. Substances involved are mainly antidepressants, antihistamines, antipsychotics, benzodiazepines, analgesics, anesthetics, psychostimulants, other opioids, alcohol, and illegal drugs of abuse. The interactions can be produced due to pharmacokinetic and pharmacodynamic mechanisms. Naloxone can be used as an antidote, although required doses might be higher than for traditional opioid intoxications. It is crucial that doctors who habitually prescribe opioids, which are often misused by patients and NPS users, be aware of designer opioids’ potentially life-threatening drug-drug interactions in order to prevent new cases of intoxication.

Molecular Modeling of Drug-Transporter Interactions-An International Transporter Consortium Perspective.

Membrane transporters play diverse roles in the pharmacokinetics and pharmacodynamics of small-molecule drugs. Understanding the mechanisms of drug-transporter interactions at the molecular level is, therefore, essential for the design of drugs with optimal therapeutic effects. This white paper examines recent progress, applications, and challenges of molecular modeling of membrane transporters, including modeling techniques that are centered on the structures of transporter ligands, and those focusing on the structures of the transporters. The goals of this article are to illustrate current best practices and future opportunities in using molecular modeling techniques to understand and predict transporter-mediated effects on drug disposition and efficacy.Membrane transporters from the solute carrier (SLC) and ATP-binding cassette (ABC) superfamilies regulate the cellular uptake, efflux, and homeostasis of many essential nutrients and significantly impact the pharmacokinetics of drugs; further, they may provide targets for novel therapeutics as well as facilitate prodrug approaches. Because of their often broad substrate selectivity they are also implicated in many undesirable and sometimes life-threatening drug-drug interactions (DDIs).5,6.

Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands

Coumarin anticoagulants are prone to potentially life-threatening drug-drug interactions due to a combination of unfavorable properties. However, real life data on the actual occurrence are scarce. The aim of this study was to quantify and qualify potential drug interactions with coumarin anticoagulants in daily practice. A cohort study including all users of phenprocoumon or acenocoumarol during the period 1991-2003 in the PHARMO Record Linkage System. All 24 individual drugs and 11 drug groups interacting with coumarins according to central database used in the Dutch pharmacies were considered. Frequency and type of potential drug interactions during anticoagulant therapy with coumarins. 48,627 out of 76,455 mainly acenocoumarol-users (64%) were dispensed at least one potentially interacting drug (PID) during anticoagulant therapy. About 35% of these cases were dispensed a (very) strongly interacting drug, whereas 3% were dispensed a contraindicated drug. Antibacterial drugs and NSAIDs (39% and 37% of all users, respectively) were the most frequently dispensed PIDs. Potential drug interactions with coumarins frequently occur in daily practice, confronting two-thirds of patients with an increased risk of bleeding. To a large part, this is attributable to commonly prescribed medication like antibacterial drugs and NSAIDs. This situation substantiates the need for proper monitoring or new anticoagulants with less drug-drug interactions.