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A limited number of prescribed drugs account for the great majority of drug-drug interactions

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to investigate the prevalence of prescribed combinations of interacting drugs in the Swedish population.

Methods

This study design was retrospective and cross-sectional, based on a national register of dispensed prescription drugs during the period from January 1 to April 30, 2010. Prescription data was linked to the drug-drug interaction database SFINX to yield the prevalence of interacting combinations dispensed in the population. The study focused in particular on C- (clinically relevant interactions that can be handled, e.g. by dose adjustments), and D-interactions (clinically relevant interactions that should be avoided).

Results

Thirty-eight and 3.8 % of the population were dispensed combinations of drugs classified as C- or D- interactions, respectively, i.e. clinically relevant, involving all therapeutic areas. Half of the D-interactions were associated with increased risk of adverse drug reactions whereas the other half were considered interactions with a potential to cause therapeutic failure. We identified a top 15 list of D-interactions that included 80 % of the total number of interacting drug combinations. Regarding individual drugs, a group of only ten drugs was involved in as much as 94 % of all D-interactions.

Conclusions

This study reveals that the majority of prescribed interacting drug combinations in Sweden involve a limited number of drugs. The findings may increase the awareness among prescribers of these most common drug interactions in clinical practice and highlight an area for pharmacological education. It may also serve as an inventory of potential interactions within different therapeutic areas for further research.

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References

  1. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N et al (1997) The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. Jama 277:307–311

    Article  PubMed  CAS  Google Scholar 

  2. Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. Jama 279:1200–1205

    Article  PubMed  CAS  Google Scholar 

  3. Mjorndal T, Boman MD, Hagg S, Backstrom M, Wiholm BE et al (2002) Adverse drug reactions as a cause for admissions to a department of internal medicine. Pharmacoepidemiol Drug Saf 11:65–72

    Article  PubMed  Google Scholar 

  4. Bergman U, Boman G, Wiholm BE (1978) Epidemiology of adverse drug reactions to phenformin and metformin. Br Med J 2:464–466

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Juurlink DN, Mamdani M, Kopp A, Laupacis A, Redelmeier DA (2003) Drug-drug interactions among elderly patients hospitalized for drug toxicity. Jama 289:1652–1658

    Article  PubMed  CAS  Google Scholar 

  6. Pirmohamed M, James S, Meakin S, Green C, Scott AK et al (2004) Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 329:15–19

    Article  PubMed  PubMed Central  Google Scholar 

  7. Becker ML, Kallewaard M, Caspers PW, Visser LE, Leufkens HG et al (2007) Hospitalisations and emergency department visits due to drug-drug interactions: a literature review. Pharmacoepidemiol Drug Saf 16:641–651

    Article  PubMed  Google Scholar 

  8. Hovstadius B, Hovstadius K, Astrand B, Petersson G (2010) Increasing polypharmacy—an individual-based study of the Swedish population 2005–2008. BMC Clin Pharmacol 10:16

    Article  PubMed  PubMed Central  Google Scholar 

  9. Becker ML, Visser LE, van Gelder T, Hofman A, Stricker BH (2008) Increasing exposure to drug-drug interactions between 1992 and 2005 in people aged > or = 55 years. Drugs Aging 25:145–152

    Article  PubMed  Google Scholar 

  10. Merlo J, Liedholm H, Lindblad U, Bjorck-Linne A, Falt J et al (2001) Prescriptions with potential drug interactions dispensed at Swedish pharmacies in January 1999: cross sectional study. BMJ 323:427–428

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Bjerrum L, Andersen M, Petersen G, Kragstrup J (2003) Exposure to potential drug interactions in primary health care. Scand J Prim Health Care 21:153–158

    Article  PubMed  Google Scholar 

  12. Wettermark B, Hammar N, Fored CM, Leimanis A, Otterblad Olausson P et al (2007) The new Swedish Prescribed Drug Register—opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 16:726–735

    Article  PubMed  Google Scholar 

  13. Bottiger Y, Laine K, Andersson ML, Korhonen T, Molin B et al (2009) SFINX—a drug-drug interaction database designed for clinical decision support systems. Eur J Clin Pharmacol 65:627–633

    Article  PubMed  Google Scholar 

  14. Marie Eliasson (2011) Project leader PASCAL. Personal communication, October, 2011

  15. Sjöqvist F (1997) A new classification system for drug interactions. Eur J Clin Pharmaco 52(Supp):327a

    Google Scholar 

  16. Statistiska Centralbyrån (SCB), Statistics Sweden, available from: http://www.scb.se/Pages/List____250612.aspx. Accessed November 2013.

  17. Mannheimer B, Eliasson E (2010) Drug-drug interactions that reduce the formation of pharmacologically active metabolites: a poorly understood problem in clinical practice. J Intern Med 268:540–548

    Article  PubMed  CAS  Google Scholar 

  18. Reis AM, Cassiani SH (2011) Prevalence of potential drug interactions in patients in an intensive care unit of a university hospital in Brazil. Clinics (Sao Paulo) 66:9–15

    Article  Google Scholar 

  19. Janchawee B, Wongpoowarak W, Owatranporn T, Chongsuvivatwong V (2005) Pharmacoepidemiologic study of potential drug interactions in outpatients of a university hospital in Thailand. J Clin Pharm Ther 30:13–20

    Article  PubMed  CAS  Google Scholar 

  20. Vonbach P, Dubied A, Beer JH, Krahenbuhl S (2007) Recognition and management of potential drug-drug interactions in patients on internal medicine wards. Eur J Clin Pharmacol 63:1075–1083

    Article  PubMed  Google Scholar 

  21. Pasina L, Djade CD, Nobili A, Tettamanti M, Franchi C et al (2013) Drug-drug interactions in a cohort of hospitalized elderly patients. Pharmacoepidemiol Drug Saf 22:1054–1060

    PubMed  Google Scholar 

  22. Egger T, Dormann H, Ahne G, Runge U, Neubert A et al (2003) Identification of adverse drug reactions in geriatric inpatients using a computerised drug database. Drugs Aging 20:769–776

    Article  PubMed  CAS  Google Scholar 

  23. Mannheimer B, Wettermark B, Lundberg M, Pettersson H, von Bahr C et al (2010) Nationwide drug-dispensing data reveal important differences in adherence to drug label recommendations on CYP2D6-dependent drug interactions. Br J Clin Pharmacol 69:411–417

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Settergren J, Eiermann B, Mannheimer B (2013) Adherence to drug label recommendations for avoiding drug interactions causing statin-induced myopathy—a nationwide register study. PLoS One 8:e69545

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Immonen S, Valvanne J, Pitkala KH (2013) The prevalence of potential alcohol-drug interactions in older adults. Scand J Prim Health Care 31:73–78

    Article  PubMed  PubMed Central  Google Scholar 

  26. Andersson ML, Bottiger Y, Lindh JD, Wettermark B, Eiermann B (2013) Impact of the drug-drug interaction database SFINX on prevalence of potentially serious drug-drug interactions in primary health care. Eur J Clin Pharmacol 69:565–571

    Article  PubMed  CAS  Google Scholar 

  27. Launiainen T, Sajantila A, Rasanen I, Vuori E, Ojanpera I (2010) Adverse interaction of warfarin and paracetamol: evidence from a post-mortem study. Eur J Clin Pharmacol 66:97–103

    Article  PubMed  CAS  Google Scholar 

  28. Launiainen T, Vuori E, Ojanpera I (2009) Prevalence of adverse drug combinations in a large post-mortem toxicology database. Int J Legal Med 123:109–115

    Article  PubMed  Google Scholar 

  29. Hosia-Randell HM, Muurinen SM, Pitkala KH (2008) Exposure to potentially inappropriate drugs and drug-drug interactions in elderly nursing home residents in Helsinki, Finland: a cross-sectional study. Drugs Aging 25:683–692

    Article  PubMed  CAS  Google Scholar 

  30. Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C et al (1989) Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid. Antimicrob Agents Chemother 33:1901–1907

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Grasela TH Jr, Schentag JJ, Sedman AJ, Wilton JH, Thomas DJ et al (1989) Inhibition of enoxacin absorption by antacids or ranitidine. Antimicrob Agents Chemother 33:615–617

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Janknegt R (1990) Drug interactions with quinolones. J Antimicrob Chemother 26(D):7–29

    Article  PubMed  CAS  Google Scholar 

  33. Preheim LC, Cuevas TA, Roccaforte JS, Mellencamp MA, Bittner MJ (1986) Ciprofloxacin and antacids. Lancet 2:48

    Article  PubMed  CAS  Google Scholar 

  34. Sindrup SH, Brosen K, Bjerring P, Arendt-Nielsen L, Larsen U et al (1990) Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. Clin Pharmacol Ther 48:686–693

    Article  PubMed  CAS  Google Scholar 

  35. Poulsen L, Arendt-Nielsen L, Brosen K, Sindrup SH (1996) The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 60:636–644

    Article  PubMed  CAS  Google Scholar 

  36. Poulsen L, Brosen K, Arendt-Nielsen L, Gram LF, Elbaek K et al (1996) Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. Eur J Clin Pharmacol 51:289–295

    Article  PubMed  CAS  Google Scholar 

  37. Desmeules J, Gascon MP, Dayer P, Magistris M (1991) Impact of environmental and genetic factors on codeine analgesia. Eur J Clin Pharmacol 41:23–26

    Article  PubMed  CAS  Google Scholar 

  38. Laine K, Tybring G, Hartter S, Andersson K, Svensson JO et al (2001) Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clin Pharmacol Ther 70:327–335

    Article  PubMed  CAS  Google Scholar 

  39. Brosen K, Hansen JG, Nielsen KK, Sindrup SH, Gram LF (1993) Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur J Clin Pharmacol 44:349–355

    Article  PubMed  CAS  Google Scholar 

  40. Budnitz DS, Lovegrove MC, Shehab N, Richards CL (2011) Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 365:2002–2012

    Article  PubMed  CAS  Google Scholar 

  41. Gasse C, Hollowell J, Meier CR, Haefeli WE (2005) Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin. Thromb Haemost 94:537–543

    PubMed  CAS  Google Scholar 

  42. Jonsson AK, Spigset O, Jacobsson I, Hagg S (2007) Cerebral haemorrhage induced by warfarin—the influence of drug-drug interactions. Pharmacoepidemiol Drug Saf 16:309–315

    Article  PubMed  Google Scholar 

  43. Johnell K, Klarin I (2007) The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register. Drug Saf 30:911–918

    Article  PubMed  Google Scholar 

  44. Lau HS, de Boer A, Beuning KS, Porsius A (1997) Validation of pharmacy records in drug exposure assessment. J Clin Epidemiol 50:619–625

    Article  PubMed  CAS  Google Scholar 

  45. Gilard M, Arnaud B, Le Gal G, Abgrall JF, Boschat J (2006) Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 4:2508–2509

    Article  PubMed  CAS  Google Scholar 

  46. Small DS, Farid NA, Payne CD, Weerakkody GJ, Li YG et al (2008) Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol 48:475–484

    Article  PubMed  CAS  Google Scholar 

  47. Sibbing D, Morath T, Stegherr J, Braun S, Vogt W et al (2009) Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 101:714–719

    PubMed  CAS  Google Scholar 

  48. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G et al (2009) Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 157(148):e141–145

    Google Scholar 

  49. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC et al (2009) A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. Cmaj 180:713–718

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kreutz RP, Stanek EJ, Aubert R, Yao J, Breall JA et al (2010) Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study. Pharmacotherapy 30:787–796

    Article  PubMed  CAS  Google Scholar 

  51. Kwok CS, Jeevanantham V, Dawn B, Loke YK (2013) No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis. Int J Cardiol 167:965–974

    Article  PubMed  Google Scholar 

  52. Gerson LB, McMahon D, Olkin I, Stave C, Rockson SG (2012) Lack of significant interactions between clopidogrel and proton pump inhibitor therapy: meta-analysis of existing literature. Dig Dis Sci 57:1304–1313

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Bengt Sjöborg for highly valuable assistance in computerized processing of the Prescribed Drug Register and the SFINX database. We also thank Ylva Böttiger and Lars L Gustafsson for valuable discussions. The study was supported by the Karolinska Institutet, the Swedish Foundation for Clinical Pharmacology and Pharmacotherapy and the Swedish Society for Medical Research.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    Johan Holm, Birgit Eiermann & Erik Eliasson

  2. Section of Diabetes and Endocrinology, Department of Internal Medicine, Karolinska Institutet, Södersjukhuset 8-10, 118 82, Södersjukhuset, Stockholm, Sweden

    Buster Mannheimer

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  1. Johan Holm
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  2. Birgit Eiermann
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  4. Buster Mannheimer
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Correspondence to Buster Mannheimer.

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Holm, J., Eiermann, B., Eliasson, E. et al. A limited number of prescribed drugs account for the great majority of drug-drug interactions. Eur J Clin Pharmacol 70, 1375–1383 (2014). https://doi.org/10.1007/s00228-014-1745-3

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  • DOI: https://doi.org/10.1007/s00228-014-1745-3

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