Proton pump inhibitors and cancer treatments: Emerging evidence against coadministration.

Background: Proton pump inhibitors (PPIs) are widely used in cancer patients despite accumulating data showing that they can impact the efficacy of major anticancer drugs. This is particularly important with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs).

Results: Most TKIs require gastric acidity for their absorption and some retrospective series demonstrated that coprescription decreases the survival benefit of some TKI use (erlotinib, gefitinib and pazopanib).

Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS).

Background: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).

Objective: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

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.

Overriding Drug-Drug Interaction Alerts in Clinical Decision Support Systems: A Scoping Review.

Ineffective computerized alerts for potential Drug-Drug Interactions (DDI) is a longstanding informatics issue. Prescribing clinicians often ignore or override such alerts due to lack of context and clinical relevance, among various other reasons. In this study, we reveiwed published data on the rate of DDI alert overrides and medications involved in the overrides.

QTc Prolongation with the Use of Hydroxychloroquine and Concomitant Arrhythmogenic Medications: A Retrospective Study Using Electronic Health Records Data.

Introduction: Hydroxychloroquine can induce QT/QTc interval prolongation for some patients; however, little is known about its interactions with other QT-prolonging drugs.

Objective: The purpose of this retrospective electronic health records study was to evaluate changes in the QTc interval in patients taking hydroxychloroquine with or without concomitant QT-prolonging medications.

Methods: De-identified health records were obtained from the Cerner Health Facts database.

Serum potassium changes due to concomitant ACEI/ARB and spironolactone therapy: A systematic review and meta-analysis.

Purpose: To provide evidence of serum potassium changes in individuals taking angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) concomitantly with spironolactone compared to ACEI/ARB therapy alone.

Methods: PubMed, Embase, Scopus, and Web of Science were searched for studies including exposure to both spironolactone and ACEI/ARB therapy compared to ACEI/ARB therapy alone. The primary outcome was serum potassium change over time.

Designing and evaluating contextualized drug-drug interaction algorithms.

Objective: Alert fatigue is a common issue with off-the-shelf clinical decision support. Most warnings for drug-drug interactions (DDIs) are overridden or ignored, likely because they lack relevance to the patient's clinical situation. Existing alerting systems for DDIs are often simplistic in nature or do not take the specific patient context into consideration, leading to overly sensitive alerts.

Risk of Bleeding with Exposure to Warfarin and Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review and Meta-Analysis.

Background:  Warfarin use can trigger the occurrence of bleeding independently or as a result of a drug-drug interaction when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs).

Objectives:  This article examines the risk of bleeding in individuals exposed to concomitant warfarin and NSAID compared with those taking warfarin alone (Prospero Registry ID 145237).

Methods:  PubMed, EMBASE, Scopus, and Web of Science were searched.

Evidence of Clinically Meaningful Drug-Drug Interaction With Concomitant Use of Colchicine and Clarithromycin.

Introduction: Colchicine is currently approved for the treatment of gout and familial Mediterranean fever, among other conditions. Clarithromycin, a strong inhibitor of CYP3A4 and P-glycoprotein, dramatically increases colchicine's half-life, augmenting the risk of a life-threatening adverse reaction when used inadvertently with colchicine.

Objectives: The aim of this study was to examine the evidence and clinical implications of concomitant use of colchicine and clarithromycin.

The Underrated Risks of Tamoxifen Drug Interactions.

Tamoxifen is a prodrug, and most of the therapeutic effect in treating breast cancer stems from its metabolite, endoxifen. Since cytochrome P450 (CYP) 2D6 is the most important enzyme in the production of endoxifen, drugs that inhibit CYP2D6 would be expected to reduce tamoxifen efficacy. In addition to drug-drug interactions (DDI) involving CYP2D6, there is growing evidence that enzyme inducers can substantially alter the disposition of endoxifen, reducing tamoxifen efficacy.

Recommendations for selecting drug-drug interactions for clinical decision support.

Purpose: Recommendations for including drug-drug interactions (DDIs) in clinical decision support (CDS) are presented.

Summary: A conference series was conducted to improve CDS for DDIs. A work group consisting of 20 experts in pharmacology, drug information, and CDS from academia, government agencies, health information vendors, and healthcare organizations was convened to address (1) the process to use for developing and maintaining a standard set of DDIs, (2) the information that should be included in a knowledge base of standard DDIs, (3) whether a list of contraindicated drug pairs can or should be established, and (4) how to more intelligently filter DDI alerts.

Clinical Weighting of Drug-Drug Interactions in Hospitalized Elderly.

Adverse drug reactions impact on patient health, effectiveness of pharmacological therapy and increased health care costs. This investigation intended to detect the most critical drug-drug interactions in hospitalized elderly patients, weighting clinical risk. We conducted a cross-sectional study between January and April 2014; all patients 70 years or older, hospitalized for >24 hr and prescribed at least one medication were included in the study.

Is digoxin use for cardiovascular disease associated with risk of prostate cancer?

Purpose: Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. Preclinical studies of prostate cancer (PCa) have shown anti-tumor activity with digoxin. We explore the relationship between use of digoxin and PCa risk.

Statin use and risk of prostate cancer: results from a population-based epidemiologic study.

Epidemiologic studies of statin use in relation to prostate cancer risk have been inconclusive. Recent evidence, however, suggests that longer-term use may reduce risk of more advanced disease. The authors conducted a population-based study of 1,001 incident prostate cancer cases diagnosed in 2002-2005 and 942 age-matched controls from King County, Washington, to evaluate risk associated with statin use.

Proposal for a new tool to evaluate drug interaction cases.

The assessment of causation for a potential drug interaction requires thoughtful consideration of the properties of both the object and precipitant drugs, patient-specific factors, and the possible contribution of other drugs that the patient may be taking. The Naranjo nomogram was designed to evaluate single-drug adverse events, not drug-drug interactions. Several of the questions on the Naranjo nomogram do not apply to potential drug-drug interactions, while others do not specify object or precipitant drug.

Assessment of potential drug-drug interactions with a prescription claims database.

Purpose: The prevalence of 25 clinically important potential drug-drug interactions (DDIs) in a population represented by the drug claims database of a pharmacy benefit management company (PBM) was studied.

Methods: A retrospective cross-sectional analysis of pharmaceutical claims for almost 46 million participants in a PBM was conducted to determine the frequency of 25 DDIs previously identified as clinically important. A DDI was counted when drugs in potentially interacting combinations were dispensed within 30 days of each other during a 25-month period between April 2000 and June 2002.

Identification of serious drug-drug interactions: results of the partnership to prevent drug-drug interactions.

Objective: To develop a list of clinically important drug-drug interactions (DDIs) likely to be encountered in community and ambulatory pharmacy settings and detected by a computerized pharmacy system.

Design: Cross-sectional, one-time evaluation.

Setting: United States in fall 2001.

Concordance of severity ratings provided in four drug interaction compendia.

Objective: To evaluate the agreement among drug-drug interaction (DDI) compendia as to designation of interactions as having the greatest clinical importance ("major" DDIs).

Design: Cross-sectional, one-time evaluation.

Setting: United States in fall 2001.

Drug interaction management.

Although thousands of articles on drug interactions have been published and numerous computerized screening systems have been developed, patients continue to suffer from adverse drug interactions. Possible methods for reducing the risk of drug interactions include improving the knowledge of health care providers, improving computerized screening systems, providing information on patient risk factors, increased use of pharmacogenetic information, more attention to drug administration risk factors, and improving patient education on drug interactions.