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Information deficits in the summary of product characteristics preclude an optimal management of drug interactions: a comparison with evidence from the literature

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Abstract

Objective

To compare comprehensiveness and accuracy of drug interaction information in the German summary of product characteristics (SPC) with current evidence from the literature and to evaluate the SPC’s usefulness with respect to management of drug interactions.

Methods

Information on clinically relevant drug interactions was compared between the SPC and three standard information sources on drug interactions (DRUGDEX, Hansten/Horn’s Drug Interactions Analysis and Management, Stockley’s Drug Interactions) according to five consecutive criteria (inclusion, appropriateness of class labelling, effect description, management recommendation, explicit dose adjustment). Using medication data of an outpatient population (n=4,949), we determined what percentage of insufficiently characterized combinations indeed occurred in outpatients treated with combination drug therapy.

Results

Only for 33% (192/579) of the evaluated combinations did SPCs provide drug interaction information equivalent to the evidence from the published literature. Of the clinically relevant drug interactions, 16% were completely missing and 51% were insufficiently characterized compared with standard sources. Explicit management recommendations were either missing or differed from standard sources in 18% of the evaluated pairs of compounds. Of these missing or insufficiently characterized combinations, 12% (47/387) were indeed prescribed to outpatients. Those drug combinations for which the interaction potential was not mentioned in the SPC were received by 0.6% (32/4,949) of patients, and 4% (192/4,949) of patients received combinations that had insufficiently characterized drug interactions.

Conclusions

If physicians only rely on SPC information for drug interactions, adverse events due to lacking management recommendations may occur. To meet the SPCs claim of being the basis of information for health professionals on how to use medicinal products safely and effectively, information on drug interactions should be thoroughly up-dated and expanded.

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References

  1. Veehof LJG, Stewart RE, Haaijer-Ruskamp FM, Meyboom-de Jong B (2000) The development of polypharmacy. A longitudinal study. Fam Pract 17:261–267

    CAS  Google Scholar 

  2. Rosholm JU, Bjerrum L, Hallas J, Worm J, Gram LF (1998) Polypharmacy and the risk of drug-drug interactions among Danish elderly. Dan Med Bull 45:210–213

    CAS  PubMed  Google Scholar 

  3. Bergk V, Gasse C, Rothenbacher D, Loew M, Brenner H, Haefeli WE (2004) Drug interactions in primary care: impact of a new algorithm on risk determination. Clin Pharmacol Ther 76:85–96

    Article  CAS  PubMed  Google Scholar 

  4. 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 60:595–602

    Article  PubMed  Google Scholar 

  5. Rawlins MD (1996) The clinical pharmacologist in drug regulation: a European perspective. Br J Clin Pharmacol 42:59–61

    Google Scholar 

  6. Rajpal A, Reidenberg MM (2003) Drug labeling should be kept current. Clin Pharmacol Ther 73:4–6

    Article  PubMed  Google Scholar 

  7. Mullen WH, Anderson IB, Kim SY, Blanc PD, Olson KR (1997) Incorrect overdose management advice in the Physicians’ Desk Reference. Ann Emerg Med 29:255–261

    CAS  PubMed  Google Scholar 

  8. Spyker DA, Harvey ED, Harvey BE, Harvey AM, Rumack BH, Peck CC, Atkinson AJ Jr, Woosley RL, Abernethy DR, Cantilena LR (2000) Assessment and reporting of clinical pharmacology information in drug labeling. Clin Pharmacol Ther 67:196–200

    Article  CAS  PubMed  Google Scholar 

  9. Cohen JS (2001) Dose discrepancies between the Physicians’ Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events. Arch Intern Med 161:957–964

    Article  CAS  PubMed  Google Scholar 

  10. European Commission (2004) Notice to applicants. A guideline on summary of product characteristics (EC). Available from: URL:http://pharmacos.eudra.org/F2/eudralex/vol-2/C/SPCGuidRev0-Dec99.pdf. Accessed May 19, 2004

  11. Marroum PJ, Gobburu J (2002) The product label: how pharmacokinetics and pharmacodynamics reach the prescriber. Clin Pharmacokinet 41:161–169

    PubMed  Google Scholar 

  12. Aronson JK (2004) Drug interactions—information, education, and the British National Formulary. Br J Clin Pharmacol 57:371–372

    Google Scholar 

  13. Anonymous (2001) Failings in treatment advice, SPCs and black triangles. Drug Ther Bull 39:25–27

    PubMed  Google Scholar 

  14. Martin-Facklam M, Rengelshausen J, Tayrouz Y, Ketabi-Kiyanvash N, Lindenmaier H, Schneider V, Bergk V, Haefeli WE (2005) Dose individualisation in patients with renal insufficiency: does drug labelling support optimal management? Eur J Clin Pharmacol 60:807–811

    Article  PubMed  Google Scholar 

  15. Klasko RK (ed) (2003) DRUGDEX System. MICROMEDEX Inc. Greenwood Village, Colorado, version used: first quarter 2003

  16. Stockley IH (2002) Stockley’s drug interactions. The Pharmaceutical Press, London

    Google Scholar 

  17. Hansten PD, Horn JR (2003) Drug interactions analysis and management. Facts and Comparisons, St. Louis

  18. Fachinformationsverzeichnis Deutschland (einschließlich EU-Zulassungen) (2003) BPI Service GmbH, Frankfurt, Germany, version used: first quarter 2003

  19. Lin JC, Ito MK, Stolley SN, Morreale AP, Marcus DB (1999) The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin. J Clin Pharmacol 39:86–90

    Article  CAS  PubMed  Google Scholar 

  20. Pan HY (1991) Clinical pharmacology of pravastatin, a selective inhibitor of HMG-CoA reductase. Eur J Clin Pharmacol 40[Suppl 1]:S15–S18

    Article  PubMed  Google Scholar 

  21. McColl A, Smith H, White P, Field J (1998) General practitioner’s perceptions of the route to evidence based medicine: a questionnaire survey. BMJ 316:361–365

    CAS  PubMed  Google Scholar 

  22. Prosser H, Almond S, Walley T (2003) Influences on GPs’ decision to prescribe new drugs-the importance of who says what. Fam Pract 20:61–68

    Article  PubMed  Google Scholar 

  23. Sjöqvist F (1997) A new classification system for drug interactions. Eur J Clin Pharmacol 52[Suppl 1]:A126

  24. Fachinformationsverzeichnis Deutschland (einschließlich EU-Zulassungen).(2004) BPI Service GmbH, Frankfurt, Germany. Available from: URL:http://www.fachinfo.de. Accessed December 15, 2004

  25. Reggi V, Balocco-Mattavelli R, Bonati M, Breton I, Figueras A, Jambert E, Kopp C, Montane E, Rago L, Rocchi F; The International Comparative Study on Drug Information Collaborative Group (2003) Prescribing information in 26 countries: a comparative study. Eur J Clin Pharmacol 59:263–270

    Article  CAS  PubMed  Google Scholar 

  26. McInnes GT, Brodie MJ (1988) Drug interactions that matter. A critical reappraisal. Drugs 36:83–110

    CAS  Google Scholar 

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Acknowledgements

This research was supported in part by the Graduiertenkolleg 793 (German Research Foundation, DFG).

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Authors and Affiliations

  1. Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Verena Bergk, Walter E. Haefeli, Christiane Gasse & Meret Martin-Facklam

  2. Department of Epidemiology, German Centre for Research on Ageing at the University of Heidelberg, Bergheimer Strasse 20, 69115, Heidelberg, Germany

    Hermann Brenner

Authors
  1. Verena Bergk
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  2. Walter E. Haefeli
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  3. Christiane Gasse
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  4. Hermann Brenner
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  5. Meret Martin-Facklam
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Correspondence to Walter E. Haefeli.

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Bergk, V., Haefeli, W.E., Gasse, C. et al. 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, 327–335 (2005). https://doi.org/10.1007/s00228-005-0943-4

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  • DOI: https://doi.org/10.1007/s00228-005-0943-4

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