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Are incorrectly used drugs more frequently involved in adverse drug reactions? A prospective study

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

Abstract

Objectives

The aims of this study were to identify and evaluate the frequency of drugs involved in adverse drug reactions (ADRs) for which recommendations of the Summary of Product Characteristics (SPC) had not been respected and to compare the percentages of drugs suspected of being the cause of ADRs when correctly and incorrectly used.

Methods

All ADRs reported to the Regional Pharmacovigilance Centre of Tours (RPC) over a period of 5 months were analysed to identify drugs used “incorrectly” defined by drug use beyond the recommendations of the SPC, i.e. drugs used when contra-indicated and/or drugs used for an off-label indication, and/or drugs used at an inappropriate dose, and/or inappropriate duration of treatment, and/or drugs used in the presence of a potentially or definitely interacting drug.

Results

Included in the study were 182 ADRs involving 182 patients. Of 642 drugs, 169 (26%) were incorrectly used and for 81 patients (44.5%) ADRs involved at least one “incorrectly” used drug. These included 10% (64 of 642) drug interactions, 7.3% (47 of 642) off-licence indications, 5% (32 of 642) inadequate dosage, 3% (20 of 642) incorrect duration of treatment and 1% (6 of 642) contraindications. “Correctly” used drugs appeared to be less often the cause of the ADRs than “incorrectly” used drugs (59.4% versus 75%, P=0.0001).

Conclusion

“Incorrectly” used drugs were more often causally linked to ADR than correctly used drugs. A meaningful number of ADRs could probably be avoided if SPC guidelines for a safe and effective drug use are carefully adhered to.

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Notes

  1. The summary of product characteristics on which the marketing authorisation is based should include: clinical indications, contraindications, adverse effects (frequency and seriousness), special precautions for use, recommendations on use in pregnancy, recommendations on use in lactation, interactions, dosage schedule and route of administration (discriminating between children, adults and the elderly), special warnings, any effects on the ability to drive or use machines and pharmaceutical incompatibilities

  2. A serious adverse event or reaction is any untoward medical occurrence that at any dose:

    • Results in death

    • Requires inpatient hospitalisation or prolongation of existing hospitalisation

    • Results in persistent or significant disability/incapacity

    • Is life threatening

  3. In the French method of imputability, the score is not continuous. The scores are:

    • Very probable (or certain for the Uppsala Monitoring Centre): a clinical event occurring in a plausible time relative to drug administration and which cannot be explained by concurrent disease. The response to withdrawal of the drug (dechallenge) should be clinically plausible, with a satisfactory rechallenge procedure if necessary.

    • Probable (or probable/likely for the Uppsala Monitoring Centre): a clinical event with a reasonable time sequence to administration of the drug, unlikely to be attributed to concurrent disease, and which follows a clinically reasonable response on withdrawal (dechallenge).

    • Possible (or possible for the Uppsala Monitoring Centre): a clinical event, with a reasonable time sequence to administrations of the drug, but which could also be explained by concurrent disease. Information on drug withdrawal may be lacking or unclear.

    • Doubtful (or unlikely for the Uppsala Monitoring Centre): a clinical event with a temporal relationship to drug administration which makes a causal relationship improbable, and in which underlying disease provides plausible explanations.

  4. Yates F (1934) Contingency tables involving small numbers and the chi-square test. Journal of the Royal Statistical Society 1, Supplement, 217–235

  5. “off label” = use of a medicine in a manner different from that recommended by the manufacturers in their product license: use in a different indication, dose, age, route or contraindication.

    “unlicensed” = modifications to a licensed medicine; particular formulations (usually a suspension) manufactured under a “special” manufacturing license (such a medicine, although produced under the standards of good manufacturing practice, has not formally been tested in clinical trials); medicine used prior to the granting of a license and imported medicine.

  6. Confidence interval at 95%

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Regional Drug Monitoring Centre, University Hospital, CHRU, 2 boulevard Tonnellé, 37044, Tours Cedex 09, France

    A. P. Jonville-Béra, F. Béra & E. Autret-Leca

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  1. A. P. Jonville-Béra
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  2. F. Béra
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  3. E. Autret-Leca
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Correspondence to A. P. Jonville-Béra.

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Jonville-Béra, A.P., Béra, F. & Autret-Leca, E. Are incorrectly used drugs more frequently involved in adverse drug reactions? A prospective study. Eur J Clin Pharmacol 61, 231–236 (2005). https://doi.org/10.1007/s00228-004-0881-6

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  • DOI: https://doi.org/10.1007/s00228-004-0881-6

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