Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Drug Safety
Published in: Drug Safety 2/2015

01-02-2015 | Original Research Article

Consensus Recommendations for Systematic Evaluation of Drug–Drug Interaction Evidence for Clinical Decision Support

Authors: Richard T. Scheife, Lisa E. Hines, Richard D. Boyce, Sophie P. Chung, Jeremiah D. Momper, Christine D. Sommer, Darrell R. Abernethy, John R. Horn, Stephen J. Sklar, Samantha K. Wong, Gretchen Jones, Mary L. Brown, Amy J. Grizzle, Susan Comes, Tricia Lee Wilkins, Clarissa Borst, Michael A. Wittie, Daniel C. Malone

Published in: Drug Safety | Issue 2/2015

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
Aspden P, Institute of Medicine (U.S.). Committee on identifying and preventing medication errors. Preventing medication errors. Washington, DC: National Academies Press; 2007.
2.
Magro L, Moretti U, Leone R. Epidemiology and characteristics of adverse drug reactions caused by drug–drug interactions. Expert Opin Drug Saf. 2012;11(1):83–94.CrossRefPubMed
3.
4.
5.
6.
Hatton RC, Rosenberg AF, Morris CT, McKelvey RP, Lewis JR. Evaluation of contraindicated drug–drug interaction alerts in a hospital setting. Ann Pharmacother. 2011;45(3):297–308.CrossRefPubMed
7.
Shah VS, Weber RJ, Nahata MC. Contradictions in contraindications for drug–drug interactions. Ann Pharmacother. 2011;45(3):409–11.CrossRefPubMed
8.
Horn JR, Hansten PD. Comment: evaluation of contraindicated drug–drug interaction alerts in a hospital setting. Ann Pharmacother. 2011;45(6):826 (author reply-7).CrossRefPubMed
9.
Kesselheim AS, Cresswell K, Phansalkar S, Bates DW, Sheikh A. Clinical decision support systems could be modified to reduce ‘alert fatigue’ while still minimizing the risk of litigation. Health Aff (Millwood). 2011;30(12):2310–7.CrossRefPubMed
10.
Saverno KR, Hines LE, Warholak TL, Grizzle AJ, Babits L, Clark C, et al. Ability of pharmacy clinical decision-support software to alert users about clinically important drug–drug interactions. J Am Med Inform Assoc. 2011;18(1):32–7.CrossRefPubMedCentralPubMed
11.
Metzger J, Welebob E, Bates DW, Lipsitz S, Classen DC. Mixed results in the safety performance of computerized physician order entry. Health Aff (Millwood). 2010;29(4):655–63.CrossRefPubMed
12.
Abarca J, Colon LR, Wang VS, Malone DC, Murphy JE, Armstrong EP. Evaluation of the performance of drug–drug interaction screening software in community and hospital pharmacies. J Manag Care Pharm. 2006;12(5):383–9.PubMed
13.
van der Sijs H, Aarts J, Vulto A, Berg M. Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc. 2006;13(2):138–47.CrossRefPubMedCentralPubMed
14.
Miller AM, Boro MS, Korman NE, Davoren JB. Provider and pharmacist responses to warfarin drug–drug interaction alerts: a study of healthcare downstream of CPOE alerts. J Am Med Inform Assoc. 2011;18(Suppl 1):i45–50.CrossRefPubMedCentralPubMed
15.
Weingart SN, Toth M, Sands DZ, Aronson MD, Davis RB, Phillips RS. Physicians’ decisions to override computerized drug alerts in primary care. Arch Intern Med. 2003;163(21):2625–31.CrossRefPubMed
16.
Grizzle AJ, Mahmood MH, Ko Y, Murphy JE, Armstrong EP, Skrepnek GH, et al. Reasons provided by prescribers when overriding drug–drug interaction alerts. Am J Manag Care. 2007. p. 573–8 (United States).
17.
Caccia S, Garattini S, Pasina L, Nobili A. Predicting the clinical relevance of drug interactions from pre-approval studies. Drug Saf. 2009;32(11):1017–39.CrossRefPubMed
18.
Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095–106CrossRefPubMed
19.
Huang SM, Strong JM, Zhang L, Reynolds KS, Nallani S, Temple R, et al. New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol. 2008;48(6):662–70.CrossRefPubMed
20.
Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41(4):674–80.CrossRefPubMed
21.
Hines LE, Malone DC, Murphy JE. Recommendations for generating, evaluating, and implementing drug–drug interaction evidence. Pharmacotherapy. 2012;32(4):304–13.CrossRefPubMed
22.
Hansten PD, Horn JR, Hazlet TK. ORCA: OpeRational ClassificAtion of drug interactions. J Am Pharm Assoc. 2001;41(2):161–5.
23.
Ridgeley MS, Greenberg MD. Too many alerts, too much liability: sorting through the malpractice implications of drug–drug interaction clinical decision support. Saint Louis Univ J Health Law Policy. 2012;5(257):257–96.
24.
Oates JA. Chapter 5. The science of drug therapy. In: Brunton LL, editor. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill, Medical Publishing Division; 2006.
25.
Hines LE, Murphy JE. Potentially harmful drug–drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011;9(6):364–77.CrossRefPubMed
26.
Talbot JCC, Aronson JK, Stephens MDB. Stephens’ detection and evaluation of adverse drug reactions : principles and practice. 6th ed. Chichester: Wiley; 2011.CrossRef
27.
28.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45.CrossRefPubMed
29.
Hutchinson TA, Lane DA. Assessing methods for causality assessment of suspected adverse drug reactions. J Clin Epidemiol. 1989;42(1):5–16.CrossRefPubMed
30.
Böttiger Y, Laine K, Andersson ML, Korhonen T, Molin B, Ovesjö ML, et al. SFINX-a drug–drug interaction database designed for clinical decision support systems. Eur J Clin Pharmacol. 2009;65(6):627–33.CrossRefPubMed
31.
van Roon EN, Flikweert S, le Comte M, Langendijk PN, Kwee-Zuiderwijk WJ, Smits P, et al. Clinical relevance of drug–drug interactions : a structured assessment procedure. Drug Saf. 2005;28(12):1131–9.CrossRefPubMed
32.
Boyce R, Collins C, Horn J, Kalet I. Computing with evidence Part II: an evidential approach to predicting metabolic drug–drug interactions. J Biomed Inform. 2009;42(6):990–1003.CrossRefPubMedCentralPubMed
33.
Boyce RD, Handler SM, Karp JF, Hanlon JT. Age-related changes in antidepressant pharmacokinetics and potential drug–drug interactions: a comparison of evidence-based literature and package insert information. Am J Geriatr Pharmacother. 2012;10(2):139–50.CrossRefPubMedCentralPubMed
34.
Boyce RD, Collins C, Clayton M, Kloke J, Horn JR. Inhibitory metabolic drug interactions with newer psychotropic drugs: inclusion in package inserts and influences of concurrence in drug interaction screening software. Ann Pharmacother. 2012;46(10):1287–98.CrossRefPubMed
35.
McDonagh MS, Peterson K, Balshem H, Helfand M. US Food and Drug Administration documents can provide unpublished evidence relevant to systematic reviews. J Clin Epidemiol. 2013;66(10):1071–81.CrossRefPubMed
36.
Turner EH. How to access and process FDA drug approval packages for use in research. BMJ. 2013;347:f5992.CrossRefPubMed
37.
38.
DiNicolantonio JJ, Serebruany VL. Challenging the FDA black box warning for high aspirin dose with ticagrelor in patients with diabetes. Diabetes. 2013;62(3):669–71.CrossRefPubMedCentralPubMed
39.
Anthony M, Romero K, Malone DC, Hines LE, Higgins L, Woosley RL. Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium. Clin Pharmacol Ther. 2009;86(4):425–9.CrossRefPubMed
40.
Chao SD, Maibach HI. Lack of drug interaction conformity in commonly used drug compendia for selected at-risk dermatologic drugs. Am J Clin Dermatol. 2005;6(2):105–11.CrossRefPubMed
41.
Hines LE, Ceron-Cabrera D, Romero K, Anthony M, Woosley RL, Armstrong EP, et al. Evaluation of warfarin drug interaction listings in US product information for warfarin and interacting drugs. Clin Ther. 2011;33(1):36–45.CrossRefPubMed
42.
43.
44.
Food and Drug Administration. Indexing structured product labeling for human prescription drug and biologic products. Docket No. FDA-2010-N-0256. Federal Register. 2010;2010(75):33312–3.
45.
Horn JR, Hansten PD. Predicting the magnitude of drug interactions: the final frontier. Pharmacy Times. 2006;72.
46.
de Leon J, Spina E, Diaz FJ. Pharmacokinetic drug interaction studies must consider pharmacological heterogeneity, use of repeated dosing, and translation into a message understandable to practicing clinicians. J Clin Psychopharmacol. 2009;29(3):201–5.CrossRefPubMed
47.
Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(6):811–9.CrossRefPubMed
48.
Floor-Schreudering A, Geerts AF, Aronson JK, Bouvy ML, Ferner RE, De Smet PA. Checklist for standardized reporting of drug–drug interaction management guidelines. Eur J Clin Pharmacol. 2014;70(3):313–8.CrossRefPubMed
49.
Verbeurgt P, Mamiya T, Oesterheld J. How common are drug and gene interactions? Prevalence in a sample of 1143 patients with CYP2C9, CYP2C19 and CYP2D6 genotyping. Pharmacogenomics. 2014;15(5):655–65.CrossRefPubMed
50.
Tamblyn R, Eguale T, Buckeridge DL, Huang A, Hanley J, Reidel K, et al. The effectiveness of a new generation of computerized drug alerts in reducing the risk of injury from drug side effects: a cluster randomized trial. J Am Med Inform Assoc. 2012;19(4):635–43.CrossRefPubMedCentralPubMed
51.
Seidling HM, Klein U, Schaier M, Czock D, Theile D, Pruszydlo MG, et al. What, if all alerts were specific—estimating the potential impact on drug interaction alert burden. Int J Med Inform. 2014;83(4):285–91.CrossRefPubMed
52.
Miura M, Tada H, Yasui-Furukori N, Uno T, Sugawara K, Tateishi T, et al. Effect of clarithromycin on the enantioselective disposition of lansoprazole in relation to CYP2C19 genotypes. Chirality. 2005;17(6):338–44.CrossRefPubMed
53.
Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ. What is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336(7651):995–8.CrossRefPubMedCentralPubMed
54.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.CrossRefPubMedCentralPubMed
55.
Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490 (2004-06-17 21:56:41).CrossRefPubMed
56.
57.
58.
59.
60.
Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther. 1994;56(6 Pt 1):601–7.CrossRefPubMed
61.
Varhe A, Olkkola KT, Neuvonen PJ. Effect of fluconazole dose on the extent of fluconazole-triazolam interaction. Br J Clin Pharmacol. 1996;42(4):465–70.CrossRefPubMedCentralPubMed
62.
Hughes BM, Small RE, Brink D, McKenzie ND. The effect of flurbiprofen on steady-state plasma lithium levels. Pharmacotherapy. 1997;17(1):113–20.PubMed
63.
Phansalkar S, Desai AA, Bell D, Yoshida E, Doole J, Czochanski M, et al. High-priority drug–drug interactions for use in electronic health records. J Am Med Inform Assoc. 2012;19(5):735–43.CrossRefPubMedCentralPubMed
64.
Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc (2003). 2004;44(2):136–41.CrossRef
65.
Murphy MK, Black NA, Lamping DL, McKee CM, Sanderson CF, Askham J, et al. Consensus development methods, and their use in clinical guideline development. Health Technol Assess. 1998;2(3):i–iv (1–88).PubMed
Metadata
Title
Consensus Recommendations for Systematic Evaluation of Drug–Drug Interaction Evidence for Clinical Decision Support
Authors
Richard T. Scheife
Lisa E. Hines
Richard D. Boyce
Sophie P. Chung
Jeremiah D. Momper
Christine D. Sommer
Darrell R. Abernethy
John R. Horn
Stephen J. Sklar
Samantha K. Wong
Gretchen Jones
Mary L. Brown
Amy J. Grizzle
Susan Comes
Tricia Lee Wilkins
Clarissa Borst
Michael A. Wittie
Daniel C. Malone
Publication date
01-02-2015
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 2/2015
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-014-0262-8

Other articles of this Issue 2/2015

Drug Safety 2/2015 Go to the issue

Original Research Article

Pediatric Drug Safety Signal Detection: A New Drug–Event Reference Set for Performance Testing of Data-Mining Methods and Systems

Review Article

Specialist Cohort Event Monitoring Studies: A New Study Method for Risk Management in Pharmacovigilance

Review Article

Cancer Chemotherapy and Cardiac Arrhythmias: A Review

Original Research Article

Effect of An Educational Intervention to Improve Adverse Drug Reaction Reporting in Physicians: A Cluster Randomized Controlled Trial

Review Article

Treating Severe Malaria in Pregnancy: A Review of the Evidence

Original Research Article

Risk of Anaphylaxis with Repeated Courses of Rasburicase: A Research on Adverse Drug Events and Reports (RADAR) Project