We have also developed two SMART-on-FHIR apps for drug-drug interactions of importance. Both SMART apps are available for testing in the Logica and OpenEpic sandboxes. Both apps are available at

  • CDS for colchicine and inhibitors of both Cytochrome P450 3A4 and P-glycoprotein: This SMART app focuses on supporting clinician decision making for situations where a patient is at risk for an adverse event due to colchicine toxicity caused by inhibition of the metabolism of colchicine by an inhibitor of both Cytochrome P450 3A4 and P-glycoprotein. The SMART app triggers on the relevant drug combinations and suggests viable alternatives to the CYP3A4 or P-gp inhibitor. The app uses data about the patient’s kidney function present in the EHR to communicate that the risk of patient harm is even greater for if the patient’s kidney function is poor.
  • CDS for tizanidine and inhibitors of Cytocrhome P450 1A2: This SMART app focuses on situations where a patient is at risk for an adverse event due to tizanidine toxicity caused by inhibition of the metabolism of tizanidine by an inhibitor of CYP1A2. This interaction is of great concern because ciprofloxacin, fluvoxamine and zafirlukast inhibit CYP1A2 and can increase the tizanidine area-under-the-concentration time curve (AUC) by more than 5-fold. Our recent study of spontaneous reports in FAERS identified safety signals between tizanidine and the CYP1A2 inhibitors ciprofloxacin (ROR for hypotension: 6.3 (95%CI: 4.7 to 8.5)), fluvoxamine (ROR for hypotension: 11.4 (95% CI: 4.5 to 28.8)), and zafirlukast (ROR for falls: 16.0 (95% CI: 95% 6.1-42.1)).



Villa Zapata, L., Boyce, RD., Chou, E., Hansten, P., Horn, J., Gephart, S.,   Subbian, V., Romero, A., Malone, D., QTc Prolongation with the Use of Hydroxychloroquine and Concomitant Arrhythmogenic Medications: A Retrospective Study Using Electronic Health Records Data. Accepted by Drugs Real World Outcomes in May 2022. PMID: 35665910 DOI: 10.1007/s40801-022-00307-5

Giannouchos TV, Gomez-Lumbreras A, Malone DC. Risk of tizanidine-induced adverse events after concomitant exposure to ciprofloxacin: A cohort study in the U.S. Am J Emerg Med. 2022 Mar 10;55:147-151. PMID: 35325788 DOI: 10.1016/j.ajem.2022.03.008

Reese TJ, Wright A Liu S, Boyce RD, Romero A, Del Fiol G, Kawamoto K, Malone DC. Improving the specificity of drug-drug interaction alerts: Can it be done? Am J Health Syst Pharm. 2022 Feb 8;zxac045. PMID: 35136935 DOI: 10.1093/ajhp/zxac045


Reese TJ, Del Fiol G, Morgan K, Hurwitz JT, Kawamoto K, Gomez-lumbreras A, Brown M, Thiess H, Vazquez SR, Nelson SD, Boyce R, Malone DC. A Shared Decision-making Tool for Drug Interactions Between Warfarin and Nonsteroidal Anti-inflammatory Drugs: Design and Usability Study. JMIR Hum Factors 2021 Oct 26;8(4):e28618. PMID: 34698649 PMCID: PMC8579222 DOI: 10.2196/28618

Villa Zapata L, Carhart BS, Horn JR, Hansten PD, Subbian V, Gephart S, Tan M, Romero A, Malone DC. Serum potassium changes due to concomitant ACEI/ARB and spironolactone therapy: A systematic review and meta-analysis. Am J Health Syst Pharm 2021 May 20; PMID: 34013341 PMCID: PMC8194784 DOI: 10.1093/ajhp/zxab215

Chou E, Royce RD, Balkan B, Subbian V, Romero A, Hansten PD, Horn JR, Gephart S, Malone DC. Designing and evaluating contextualized drug-drug interaction algorithms. JAMIA Open 2021 Mar 19;4(1). PMID: 33763631 PMCID: PMC7976224 DOI: 10.1093/jamiaopen/ooab023 .


Villa Zapata L, Hansten PD, Panic J, Horn JR, Boyce RD, Gephart S, Subbian V, Romero A, Malone DC. Risk of Bleeding with Exposure to Warfarin and Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review and Meta-Analysis. Thromb Haemost 2020 July;120(7):1066-1074 PMID: 32455439 PMCID: PMC7665225 DOI: 10.1055/s-0040-1710592

Villa Zapata L, Hansten PD, Horn JR, Boyce RD, Gephart S, Subbian V, Romero A, Malone DC. Evidence of Clinically Meaningful Drug–Drug Interaction With Concomitant Use of Colchicine and Clarithromycin. Drug Saf 2020 July; 43(7):661-668 PMID: 32274687 PMCID: PMC7592308 DOI: 10.1007/s40264-020-00930-7

Poster Presentations


Kravchenko OV, Gomez Lumbreras A, Kocis PT, Malone DC, Leonard CE, Boyce RD Using N3C Enclave for Drug-Drug Interaction studies: the case of DOAC-Dexamethasone Interaction and the risk of Thrombosis. AMIA Informatics Summit. Chicago Illinois. March 22, 2022.

Sibilla MA., Malone DC., Del Fiol G., Boyce RD. Testing a Novel Tool for the Development of Drug-drug Interaction Clinical Decision Support. Accepted to the 2022 AMIA Informatics Summit. Chicago, Illinois. March 24, 2022

Kharat A, Tan M, Gomez-Lumbreras A, Zapata LV, Malone DC. An Evaluation of the Relationship between QTc Prolonging Medications, Tisdale Risk Scores and Mortality Using a Nationally Representative Electronic Health Records Database. ISPOR Annual Meeting, Washington DC, May 17, 2022


Zhang T, Gephart S, Subbian V, Boyce RD, Villa Zapata L, Hansten PD, Horn JR, Romero A, Malone DC. Barriers and Facilitators to Adoption of Drug-Drug Interaction Clinical Decision Support in US Healthcare Organizations.  Academy Health 2021 Dec. 15, 2021.

Zapata L, Subbian V, Boyce RD, Hansten PD, Horn JR, Gephart S, Romero A, Malone DC. Overriding Drug-Drug Interaction Alerts in Clinical Decision Support Systems: A Scoping Review. MEDINFO’21 (IMIA) Sept. 26, 2021.

Gomez-Lumbreras A, Boyce RD, Villa Zapata L, Hansten PD, Malone DC. Colchicine and cyp3a4/p-gp Inhibitors Interaction Signal Detection Using FAERS.  International Society for Pharmacoepidemiology 2021 Aug. 24, 2021

Zapata LV, Boyce RD, Gomez-Lumbreras A, Horn JR, Malone DC. Detecting Tizanidine and Cyp1a2 Inhibitor Interaction Signals Using the Food and Drug Administration’s Adverse Event Reporting System. International Society for Pharmacoepidemiology 2021 Aug 25, 2021


Boyce, RD. Contextualized drug-drug interaction decision support. Presentation at the 19th General Meetings of HSPC/CIIC. October 7th, 2019. University of Pittsburgh, Pittsburgh, PA.

Malone DC. Drug interaction clinical decision support: mending the medication safety net. Science in the
Desert. February 22, 2019, University of Arizona Phoenix Health Science Center, Phoenix, AZ.