European Journal of Clinical Pharmacology

, Volume 74, Issue 4, pp 525–534 | Cite as

Prevalence and nature of statin drug-drug interactions in a university hospital by electronic health record mining

  • Camille Morival
  • Richard Westerlynck
  • Guillaume Bouzillé
  • Marc Cuggia
  • Pascal Le Corre
Pharmacoepidemiology and Prescription

Abstract

Aim

Our aim was to describe prevalence, nature, and level of severity of potential statin drug-drug interactions in a university hospital.

Methods

In a cross-sectional study, statin drug-drug interactions were screened from medical record of 10,506 in-patients treated stored in the clinical data warehouse “eHOP.” We screened drug-drug interactions using Theriaque and Micromedex drug databases.

Results

A total of 22.5% of patients were exposed to at least one statin drug-drug interaction. Given their lipophilicity and CYP3A4 metabolic pathway, atorvastatin and simvastatin presented a higher prevalence of drug-drug interactions while fluvastatin presented the lowest prevalence. Up to 1% of the patients was exposed to a contraindicated drug-drug interaction, the most frequent drug-drug interaction involving influx-transporter (i.e., OATP1B1) interactions between simvastatin or rosuvastatin with cyclosporin. The second most frequent contraindicated drug-drug interaction involved CYP3A4 interaction between atorvastatin or simvastatin with either posaconazole or erythromycin. Furthermore, our analysis showed some discrepancies between Theriaque and Micromedex in the prevalence and the nature of drug-drug interactions.

Conclusions

Different drug-drug interaction profiles were observed between statins with a higher prevalence of CYP3A4-based interactions for lipophilic statins. Analyzing the three most frequent DDIs, the more significant DDIs (level 1: contraindication) were reported for transporter-based DDI involving OATP1B1 influx transporter. These points are of concern to improve prescriptions of statins.

Keywords

Statins Pharmacokinetics Drug-drug interactions Metabolic enzymes Drug transporters Drug databases Data mining Clinical data warehouse 

Notes

Compliance with ethical standards

The ethics comitee of our institution approved the study with a waiver of patient consent authorization (number 17.60). Since the design of the study is retrospective no formal consent is required.

Supplementary material

228_2017_2400_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 12 kb).

References

  1. 1.
    Gu Q, Paulose-Ram R, Burt VL, Kit BK (2014) Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003-2012. NCHS Data Brief 177:1–8Google Scholar
  2. 2.
    ANSM: Agence nationale de sécurité du médicament et des produits de santé [Internet]. [cited 2017May 17]. Available from:http://www.ansm.sante.fr/searchengine/detail/(cis)/69358900/(limit)/90
  3. 3.
    Ganga HV, Slim HB, Thompson PD (2014) A systematic review of statin-induced muscle problems in clinical trials. Am Heart J 168(1):6–15.  https://doi.org/10.1016/j.ahj.2014.03.019 CrossRefPubMedGoogle Scholar
  4. 4.
    Law M, Rudnicka AR (2006) Statin safety: a systematic review. Am J Cardiol 97(8A):52C–60C.  https://doi.org/10.1016/j.amjcard.2005.12.010 CrossRefPubMedGoogle Scholar
  5. 5.
    Stewart D, Mair A, Wilson M, Kardas P, Lewek P, Alonso A, McIntosh J, MacLure K, SIMPATHY consortium (2017) Guidance to manage inappropriate polypharmacy in older people: systematic review and future developments. Expert Opin Drug Saf 16(2):203–213.  https://doi.org/10.1080/14740338.2017.1265503 PubMedGoogle Scholar
  6. 6.
    Thai M, Reeve E, Hilmer SN, Qi K, Pearson S-A, Gnjidic D (2016) Prevalence of statin-drug interactions in older people: a systematic review. Eur J Clin Pharmacol 72(5):513–521.  https://doi.org/10.1007/s00228-016-2011-7 CrossRefPubMedGoogle Scholar
  7. 7.
    Egger SS, Rätz Bravo AE, Hess L, Schlienger RG, Krähenbühl S (2007) Age-related differences in the prevalence of potential drug-drug interactions in ambulatory dyslipidaemic patients treated with statins. Drugs Aging 24(5):429–440.  https://doi.org/10.2165/00002512-200724050-00006 CrossRefPubMedGoogle Scholar
  8. 8.
    Delamarre D, Bouzille G, Dalleau K, Courtel D, Cuggia M (2015) Semantic integration of medication data into the EHOP clinical data warehouse. Stud Health Technol Inform 210:702–706PubMedGoogle Scholar
  9. 9.
    Thériaque [Internet]. [cited 2017May 17]. Available from:http://www.theriaque.org/apps/contenu/accueil.php
  10. 10.
    Truven Health Products: Please Login [Internet]. [cited 2017May 17]. Available from:https://www.micromedexsolutions.com/home/dispatch
  11. 11.
    Interactions médicamenteuses - ANSM: Agence nationale de sécurité du médicament et des produits de santé [Internet]. [cited 2017May 17]. Available from:http://ansm.sante.fr/Dossiers/Interactions-medicamenteuses/Interactions-medicamenteuses/(offset)/0
  12. 12.
    Jaccard P (1907) La distribution de la flore dans la zone alpine. Vol. 18. 961 pGoogle Scholar
  13. 13.
    Kruskal WH (1958) Ordinal measures of association. J Am Stat Assoc 53(284):814–861.  https://doi.org/10.1080/01621459.1958.10501481 CrossRefGoogle Scholar
  14. 14.
    UCSF-FDA TransPortal [Internet]. [cited 2017May 17]. Available from:http://transportal.compbio.ucsf.edu/
  15. 15.
    DrugBank [Internet]. [cited 2017 Jan13];Available from: https://www.drugbank.ca/
  16. 16.
    Kalliokoski A, Niemi M (2009) Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158(3):693–705.  https://doi.org/10.1111/j.1476-5381.2009.00430.x CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Abarca J, Colon LR, Wang VS, Malone DC, Murphy JE, Armstrong EP (2006) Evaluation of the performance of drug-drug interaction screening software in community and hospital pharmacies. J Manag Care Pharm 12(5):383–389.  https://doi.org/10.18553/jmcp.2006.12.5.383 PubMedGoogle Scholar
  18. 18.
    Zhang T (2015) Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for atorvastatin and its metabolites. Eur J Pharm Sci 77:216–229.  https://doi.org/10.1016/j.ejps.2015.06.019 CrossRefPubMedGoogle Scholar
  19. 19.
    Yu J, Zhou Z, Tay-Sontheimer J, Levy RH, Ragueneau-Majlessi I (2017) Intestinal drug interactions mediated by OATPs: asystematic review of preclinical and clinical findings. J Pharm Sci 106(9):2312–2325.  https://doi.org/10.1016/j.xphs.2017.04.004 CrossRefPubMedGoogle Scholar
  20. 20.
    Lund M, Petersen TS, Dalhoff KP (2017) Clinical implications of P-glycoprotein modulation in drug-drug interactions. Drugs 77(8):859–883.  https://doi.org/10.1007/s40265-017-0729-x CrossRefPubMedGoogle Scholar
  21. 21.
    Ivanyuk A, Livio F, Biollaz J, Buclin T (2017) Renal drug transporters and drug interactions. Clin Pharmacokinet 56(8):825–892.  https://doi.org/10.1007/s40262-017-0506-8 CrossRefPubMedGoogle Scholar
  22. 22.
    Ramos GV, Guaraldo L, Japiassú AM, Bozza FA (2015) Comparison of two databases to detect potential drug-drug interactions between prescriptions of HIV/AIDS patients in critical care. J Clin Pharm Ther 40(1):63–67.  https://doi.org/10.1111/jcpt.12222 CrossRefPubMedGoogle Scholar
  23. 23.
    Fernández de Palencia Espinosa MÁ, Díaz Carrasco MS, Alonso Romero JL, de la Rubia Nieto A, Espuny Miró A (2015) Potential drug-drug interactions in oncological adult inpatients at a Spanish hospital: epidemiology and risk factors. Int J Clin Pharm 37(6):1021–1027.  https://doi.org/10.1007/s11096-015-0195-z CrossRefPubMedGoogle Scholar
  24. 24.
    Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, Lipton RB (2004) Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc (2003) 44(2):136–141CrossRefGoogle Scholar
  25. 25.
    Wang LM, Wong M, Lightwood JM, Cheng CM (2010) Black box warning contraindicated comedications: concordance among three major drug interaction screening programs. Ann Pharmacother 44(1):28–34.  https://doi.org/10.1345/aph.1M475 CrossRefPubMedGoogle Scholar
  26. 26.
    Vonbach P, Dubied A, Krähenbühl S, Beer JH (2008) Evaluation of frequently used drug interaction screening programs. Pharm World Sci 30(4):367–374.  https://doi.org/10.1007/s11096-008-9191-x CrossRefPubMedGoogle Scholar
  27. 27.
    Wiggins BS, Saseen JJ, Page RL, Reed BN, Sneed K, Kostis JB et al (2016) Recommendations for Management of Clinically Significant Drug-Drug Interactions with Statins and Select Agents Used in patients with cardiovascular disease: ascientific statement from the American Heart Association. Circulation 134(21):e468–e495.  https://doi.org/10.1161/CIR.0000000000000456 CrossRefPubMedGoogle Scholar
  28. 28.
    Campana C, Regazzi MB, Buggia I, Molinaro M (1996) Clinically significant drug interactions with cyclosporin. An update. Clin Pharmacokinet 30(2):141–179.  https://doi.org/10.2165/00003088-199630020-00004 CrossRefPubMedGoogle Scholar
  29. 29.
    Scheife RT, Hines LE, Boyce RD, Chung SP, Momper JD, Sommer CD, Abernethy DR, Horn JR, Sklar SJ, Wong SK, Jones G, Brown ML, Grizzle AJ, Comes S, Wilkins TL, Borst C, Wittie MA, Malone DC (2015) Consensus recommendations for systematic evaluation of drug-drug interaction evidence for clinical decision support. Drug Saf 38(2):197–206.  https://doi.org/10.1007/s40264-014-0262-8 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Phansalkar S, Desai AA, Bell D, Yoshida E, Doole J, Czochanski M, Middleton B, Bates DW (2012) High-priority drug-drug interactions for use in electronic health records. J Am Med Inform Assoc 19(5):735–743.  https://doi.org/10.1136/amiajnl-2011-000612 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Vitry AI (2007) Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol 63(6):709–714.  https://doi.org/10.1111/j.1365-2125.2006.02809.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.CHU Rennes, Pôle PharmacieService Hospitalo-Universitaire de PharmacieRennes CedexFrance
  2. 2.CHU Rennes, CIC Inserm 1414RennesFrance
  3. 3.Université de Rennes 1, LTSI, Inserm U1099RennesFrance
  4. 4.Laboratoire de Pharmacie Galénique, Laboratoire de Biopharmacie et Pharmacie Clinique, IRSET U1085, Faculté de PharmacieUniversité de Rennes 1Rennes CedexFrance
  5. 5.CHU Rennes, Centre de Données CliniquesRennesFrance
  6. 6.Ecole nationale de la statistique et de l’analyse de l’informationRennesFrance

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