Patient-centered Outcomes with Concomitant Use of Proton Pump Inhibitors and Other Drugs.

PURPOSE: We performed a systematic review of patient-centered outcomes after the concomitant use of proton pump inhibitors (PPIs) and other drugs. METHODS: We searched 4 databases in July 2016 to find studies that reported mortality and morbidity after the concomitant use of PPIs and other drugs. We conducted direct meta-analyses using a random-effects model and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. FINDINGS: We included data from 17 systematic reviews and meta-analyses, 16 randomized controlled trials, and 16 observational studies that examined the concomitant use of PPIs with medications from 10 drug classes. Low-quality evidence suggests that the use of PPIs is associated with greater morbidity when administered with antiplatelet drugs, bisphosphonates, antibiotics, anticoagulants, metformin, mycophenolate mofetil, or nelfinavir. Concomitant PPIs reduce drug-induced gastrointestinal bleeding and are associated with greater docetaxel and cisplatin response rates in patients with metastatic breast cancer. For demonstrated statistically significant relative risks and benefits from concomitant PPIs, the magnitudes of the effects are small, with <100 attributable events per 1000 patients treated, and the effects are inconsistent among specific drugs. Among individual PPIs, the concomitant use of pantoprazole or esomeprazole, but not omeprazole or lansoprazole, is associated with an increased risk for all-cause mortality, nonfatal myocardial infarction, or stroke. Clopidogrel is associated with a greater risk for myocardial infarction compared with prasugrel. Conflicting results between randomized controlled trials and observational studies and high risk for bias in the body of evidence lessened our confidence in the results. IMPLICATIONS: Available evidence suggests a greater risk for adverse patient outcomes after the concomitant use of PPIs and medications from 9 drug classes and warns against inappropriate drug combinations.

Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clinical decision support.

BACKGROUND: Healthcare organizations, compendia, and drug knowledgebase vendors use varying methods to evaluate and synthesize evidence on drug-drug interactions (DDIs). This situation has a negative effect on electronic prescribing and medication information systems that warn clinicians of potentially harmful medication combinations. OBJECTIVE: The aim of this study was to provide recommendations for systematic evaluation of evidence for DDIs from the scientific literature, drug product labeling, and regulatory documents. METHODS: A conference series was conducted to develop a structured process to improve the quality of DDI alerting systems. Three expert workgroups were assembled to address the goals of the conference. The Evidence Workgroup consisted of 18 individuals with expertise in pharmacology, drug information, biomedical informatics, and clinical decision support. Workgroup members met via webinar 12 times from January 2013 to February 2014. Two in-person meetings were conducted in May and September 2013 to reach consensus on recommendations. RESULTS: We developed expert consensus answers to the following three key questions. (i) What is the best approach to evaluate DDI evidence? (ii) What evidence is required for a DDI to be applicable to an entire class of drugs? (iii) How should a structured evaluation process be vetted and validated? CONCLUSION: Evidence-based decision support for DDIs requires consistent application of transparent and systematic methods to evaluate the evidence. Drug compendia and clinical decision support systems in which these recommendations are implemented should be able to provide higher-quality information about DDIs.