Abstract
Purpose
The project aimed to evaluate the completeness of drug-drug interaction (DDI)-related information in package inserts (PIs) and develop a systematic approach to conduct the evaluation.
Methods
DDI-related information in the branded PIs of statins, macrolides, protease inhibitors and selected drugs of narrow therapeutic index (DNTI) were evaluated against the criteria distilled from the Food and Drug Administration (FDA) labelling recommendation guidance document. Decision trees were crafted and employed in the evaluation process. Scores were computed to give each PI an overall completeness score and individual criterion completeness score. The Kruskal-Wallis test and Dunn’s multiple comparison test were used to assess the differences in the completeness scores.
Results
The mean overall completeness score of the 21 PIs was 35.7 ± 13.4 % (range 12.2–62 %). Eight out of the 11 individual evaluation criterion had a mean completeness score below 50 %. A subclass analysis conducted revealed that PIs from the different drug classes differed in the type of DDI-related information, such that they are more complete or less complete.
Conclusion
The completeness score of DDI-related information in the PIs varied extensively amongst and within drug classes. A consensus between the authorities and drug companies on the type and quality of DDI-related information to be included could improve their completeness in PIs and make PIs a valuable source of DDI reference. Decision trees, albeit not validated yet, lay the groundwork for a valuable tool to evaluate DDI-related or other drug information.
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References
Rowland MTT Clinical pharmacokinetics and pharmacodynamics: concepts and applications. Wolters Kluwer Health/Lippincott William & Wilkins, Baltimore, MD, Philadelphia, PA
Becker ML, Kallewaard M, Caspers PW, Visser LE, Leufkens HG, Stricker BH (2007) Hospitalisations and emergency department visits due to drug-drug interactions: a literature review. Pharmacoepidemiol Drug Saf 16(6):641–651. doi:10.1002/pds.1351
McDonnell PJ, Jacobs MR (2002) Hospital admissions resulting from preventable adverse drug reactions. Ann Pharmacother 36(9):1331–1336
Ko Y, Malone DC, Skrepnek GH, Armstrong EP, Murphy JE, Abarca J, Rehfeld RA, Reel SJ, Woosley RL (2008) Prescribers’ knowledge of and sources of information for potential drug-drug interactions: a postal survey of US prescribers. Drug Saf 31(6):525–536
Ko Y, Abarca J, Malone DC, Dare DC, Geraets D, Houranieh A, Jones WN, Nichol WP, Schepers GP, Wilhardt M (2007) Practitioners’ views on computerized drug-drug interaction alerts in the VA system. J Am Med Inform Assoc 14(1):56–64. doi:10.1197/jamia.M2224
Mille F, Schwartz C, Brion F, Fontan JE, Bourdon O, Degoulet P, Jaulent MC (2008) Analysis of overridden alerts in a drug-drug interaction detection system. Int J Qual Health Care 20(6):400–405. doi:10.1093/intqhc/mzn038
Miller AM, Boro MS, Korman NE, Davoren JB (2011) Provider and pharmacist responses to warfarin drug-drug interaction alerts: a study of healthcare downstream of CPOE alerts. J Am Med Inform Assoc 18(Suppl 1):i45–i50. doi:10.1136/amiajnl-2011-000262
Saverno KR, Hines LE, Warholak TL, Grizzle AJ, Babits L, Clark C, Taylor AM, Malone DC (2011) Ability of pharmacy clinical decision-support software to alert users about clinically important drug-drug interactions. J Am Med Inform Assoc 18(1):32–37. doi:10.1136/jamia.2010.007609
Wong PS, Ko Y, Sklar GE (2009) Identification and evaluation of pharmacists’ commonly used drug information sources. Ann Pharmacother 43(2):347–352. doi:10.1345/aph.1L333
Peters LB, Bahr N, Bodenreider O (2015) Evaluating drug-drug interaction information in NDF-RT and DrugBank. J Biomed Semantics 6:19. doi:10.1186/s13326-015-0018-0
Vitry AI (2007) Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol 63(6):709–714. doi:10.1111/j.1365-2125.2006.02809.x
Wong CM, Ko Y, Chan A (2008) Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: profiling and comparison of two drug compendia. Ann Pharmacother 42(12):1737–1748. doi:10.1345/aph.1L255
van Boxtel CJ, Santoso B, Edwards I Ralph (2003) Drug benefits and risks: International Textbook of Clinical Pharmacology. John Wiley & Sons Ltd, Chichester, West Syssex
Piorkowski JD Jr (2004) Bayer’s response to “potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis”. JAMA 292(21):2655–2657 . doi:10.1001/jama.292.21.2655discussion 2658-2659
Psaty BM, Furberg CD, Ray WA, Weiss NS (2004) Potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis. JAMA 292(21):2622–2631. doi:10.1001/jama.292.21.2622
Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R (2004) Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 292(21):2585–2590. doi:10.1001/jama.292.21.2585
Diasio RB (1998) Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase. Br J Clin Pharmacol 46(1):1–4
Welfare MoHa (1997) Guidelines for package inserts for prescription drugs, notification no. 606 of Pharmaceutical Affairs Bureau. In: Welfare TMoHa (ed)
Welfare MoHa (1997) Guidelines for package inserts for prescription drugs, notification no. 59 of the safety division, Pharmaceutical Affairs Bureau. In: Welfare TMoHa (ed)
Welfare MoHa (1997) Ministry of Health and Welfare (1997) Guidelines for precautions for prescription drugs, notification no. 607 of Pharmaceutical Affairs Bureau. In: Welfare TMoHa (ed)
Al-Aqeel SA (2012) Evaluation of medication package inserts in Saudi Arabia. Drug Healthc Patient Saf 4:33–38. doi:10.2147/dhps.s29402
Diobi K, Fakeye TO, Adisa R (2013) Community pharmacists’ perception of the relevance of drug package insert as source of drug information in southwestern Nigeria. Trop J Pharm Res 12(3):439–443. doi:10.4314/tjpr.v12i3.25
Solanki iN, Chhaiya SB, Mehta DS, Trivedi M, Acharya T, Patel D (2015) Analytical evaluation of drug package inserts in India. Int J Basic Clin Pharmacol 4(2):322–324
Bergk V, Haefeli WE, Gasse C, Brenner H, Martin-Facklam M (2005) Information deficits in the summary of product characteristics preclude an optimal management of drug interactions: a comparison with evidence from the literature. Eur J Clin Pharmacol 61(5–6):327–335. doi:10.1007/s00228-005-0943-4
Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R (2005) Comparison of information on the pharmacokinetic interactions of Ca antagonists in the package inserts from three countries (Japan, USA and UK). Eur J Clin Pharmacol 61(7):531–536. doi:10.1007/s00228-005-0974-x
Saito M, Hirata-Koizumi M, Urano T, Miyake S, Hasegawa R (2005) A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan. J Clin Pharm Ther 30(1):21–37. doi:10.1111/j.1365-2710.2004.00605.x
U.S. Department of Health and Human Services FDA, Center for Drug Evaluation and Research (CDER) (2012) Guidance for industry drug interaction studies—study design, data analysis, implications for dosing, and labeling recommendations In: ed., p 58–62
Contarino MF, Groot PF, van der Meer JN, Bour LJ, Speelman JD, Nederveen AJ, van den Munckhof P, Tijssen MA, Schuurman PR, van Rootselaar AF (2012) Is there a role for combined EMG-fMRI in exploring the pathophysiology of essential tremor and improving functional neurosurgery? PLoS One 7(10):e46234. doi:10.1371/journal.pone.0046234
Lin JH, Lu AY (1998) Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet 35(5):361–390. doi:10.2165/00003088-199835050-00003
Peng CC, Glassman PA, Marks IR, Fowler C, Castiglione B, Good CB (2003) Retrospective drug utilization review: incidence of clinically relevant potential drug-drug interactions in a large ambulatory population. J Manag Care Pharm 9(6):513–522
Cotel F, Exley R, Cragg SJ, Perrier J-F (2013) Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation. Proc Natl Acad Sci 110(12):4774–4779. doi:10.1073/pnas.1216150110
Novartis Pharma Lescol (fluvastatin) (2012). Package insert. Basel, Switzerland ,CH. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015
MSD Pharma. Zocor (simvastatin) (2014). package insert. Singapore, SG. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015
Pfizer. Lipitor (atorvastatin) (2014). Package insert. New York, US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015
AstraZeneca UK Ltd. Crestor (rosuvastatin) (2015). Package insert. Macclesfield, Cheshire ,UK. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015
Sanofi aventis. Ketek (telithromycin) (2006). Package insert. Italy, IT. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015
Abbott. Klacid (clarithromycin) (2014). Package insert. United States, US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015.
Pfizer. Zithromax (azithromycin) (2015). Package insert. New York, US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 10 Aug 2015
Merck & Co. Crixivan (indinavir) (2012). Package insert. New Jersey, US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Bristol-Myers Squibb. Reyataz (atazanavir) (2014). Package insert. Indiana, US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Johnson & Johnson. Prezista (darunavir) (2014). Package insert. Singapore, SG. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Aesica Queenborough. Norvir (ritonavir) (2014). Package insert. Florida,US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
MSD. Victrelis (boceprevir) (2014). Package insert. Singapore, SG. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
AbbVie. Kaletra (lopinavir/ritonavir) (2015). Package insert. North Chicago, US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Bristol-Myers Squibb. Sunvepra (asunaprevir) (2015). Package insert. Singapore, SG. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Bristol-Myers Squibb. Taxol (paclitaxel) (2013). Package insert. Sermoneta, Latina, IT. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
AmdiPharma. Cafergot (ergotamine) (2013). Package insert. Ireland, IE. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
GlaxoSmithKline. Marevan (warfarin) (2014). Package insert. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Novartis Pharma. Sandimmun Neoral (ciclosporin) (2014). Package insert. Basel, CH. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Astellas Pharma. Advagraf (tacrolimus) (2014). Package insert. Killorglin, Co. Kerry, IE. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Pfizer. Rapamune (sirolimus) (2015). Package insert. Singapore, SG. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Pfizer. Dilantin (phenytoin) (2015). Package insert. New York ,US. Available from: http://eservice.hsa.gov.sg/prism/common/enquirepublic/SearchDRBProduct.do?action=load. Accessed 1 Nov 2015
Moura CS, Acurcio FA, Belo NO (2009) Drug-drug interactions associated with length of stay and cost of hospitalization. J Pharm Pharm Sci 12(3):266–272
Rivkin A, Yin H (2011) Evaluation of the role of the critical care pharmacist in identifying and avoiding or minimizing significant drug-drug interactions in medical intensive care patients. J Crit Care 26(1):104 e101–104 e106. doi:10.1016/j.jcrc.2010.04.014
Bergk V, Gasse C, Schnell R, Haefeli WE (2004) Requirements for a successful implementation of drug interaction information systems in general practice: results of a questionnaire survey in Germany. Eur J Clin Pharmacol 60(8):595–602. doi:10.1007/s00228-004-0812-6
Yap KY-L, Chan A, Chui WK (2010) Opinions on drug interaction sources in anticancer treatments and parameters for an oncology-specific database by pharmacy practitioners in Asia. Health Services Insights 3:1
Pursnani A, Massaro JM, D’Agostino RB Sr, O’Donnell CJ, Hoffmann U (2015) Guideline-based statin eligibility, coronary artery calcification, and cardiovascular events. JAMA 314(2):134–141. doi:10.1001/jama.2015.7515
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW (2014) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol 63(25 Pt B):2889–2934. doi:10.1016/j.jacc.2013.11.002
Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N Engl J Med 338(13):853–860. doi:10.1056/nejm199803263381301
Charvet-Berard AI, Chopard P, Perneger TV (2008) Measuring quality of patient information documents with an expanded EQIP scale. Patient Educ Couns 70(3):407–411. doi:10.1016/j.pec.2007.11.018
Rees CE, Ford JE, Sheard CE (2002) Evaluating the reliability of DISCERN: a tool for assessing the quality of written patient information on treatment choices. Patient Educ Couns 47(3):273–275
Yap KY, Raaj S, Chan A (2010) OncoRx-IQ: a tool for quality assessment of online anticancer drug interactions. Int J Qual Health Care 22(2):93–106. doi:10.1093/intqhc/mzq004
Acknowledgments
This work was supported by the NUS Pharmacy Final Year Project Grant (C148-000-003-001).
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Ng, G.Q., Sklar, G.E. & Chng, H.T. An evaluation of the completeness of drug-drug interaction-related information in package inserts. Eur J Clin Pharmacol 73, 165–174 (2017). https://doi.org/10.1007/s00228-016-2151-9
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DOI: https://doi.org/10.1007/s00228-016-2151-9