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International Journal of Clinical Pharmacy

, Volume 41, Issue 5, pp 1143–1147 | Cite as

Drug safety surveillance within a strategy for the management of non-chemotherapy drug-induced neutropenia

  • José Luis Revuelta-HerreroEmail author
  • Raquel García-Sánchez
  • Javier Anguita-Velasco
  • Ana de Lorenzo-Pinto
  • Cristina Ortega-Navarro
  • María Sanjurjo-Sáez
Short Research Report
  • 182 Downloads

Abstract

Background Severe non-chemotherapy drug-induced neutropenia is a rare idiosyncratic drug reaction that is considered potentially fatal. Objective To report, in terms of drug safety surveillance, the results of an institutional strategy for NCDIN. Method An observational and prospective study including all adult patients who received filgrastim for the treatment of NCDIN from June 2015 to December 2017 was carried out by hematologists and clinical pharmacists. Results 13 patients with severe NCDIN were included in the study. The median age was 51 (range 24–80) years old and 46.2% were male. Seven patients had one or more negative prognostic factors (age > 65 years, renal impairment, autoimmune diseases and/or a neutrophil count at diagnosis < 0.1 × 109 cells/L). A single drug was identified as causative in 3 patients, while in 10 cases, 2–3 drugs were considered as potentially causative. The most frequent drugs were metamizole, piperacillin/tazobactam, dexketoprofen and linezolid, among others. Seven patients developed NCDIN during their hospital stay while 6 were admitted to the emergency department. Patients were using a median of 11 drugs (IQR 8–15) at the time of diagnosis. No deaths were recorded. Conclusion Metamizole and piperacillin/tazobactam are the most common drugs linked to non-chemotherapy drug-induced neutropenia in our cohort.

Keywords

Agranulocytosis Dipyrone Febrile neutropenia Granulocyte colony-stimulating factor Pharmacovigilance 

Notes

Acknowledgements

The authors would like to express their gratitude to the patients for their generous participation in this study.

Funding

This paper has not received any funding.

Conflicts of interest

The authors have no significant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

References

  1. 1.
    Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146(9):657–65.CrossRefGoogle Scholar
  2. 2.
    Andrès E, Mourot-Cottet R. Non-chemotherapy drug-induced neutropenia—an update. Expert Opin Drug Saf. 2017;16(11):1235–42.CrossRefGoogle Scholar
  3. 3.
    Alvir JM, Lieberman JA, Safferman AZ, et al. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993;329(3):162–7.CrossRefGoogle Scholar
  4. 4.
    Strom BL, Carson JL, Schinnar R, et al. Descriptive epidemiology of agranulocytosis. Arch Intern Med. 1992;152(7):1475–80.CrossRefGoogle Scholar
  5. 5.
    Kaufman DW, Kelly JP, Issaragrisil S, Laporte J-R, Anderson T, Levy M, et al. Relative incidence of agranulocytosis and aplastic anemia. Am J Hematol. 2006;81(1):65–7.CrossRefGoogle Scholar
  6. 6.
    Fattinger K, Roos M, Vergères P, et al. Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine. Br J Clin Pharmacol. 2000;49(2):158–67.CrossRefGoogle Scholar
  7. 7.
    Tesfa D, Keisu M, Palmblad J. Idiosyncratic drug-induced agranulocytosis: possible mechanisms and management. Am J Hematol. 2009;84(7):428–34.CrossRefGoogle Scholar
  8. 8.
    Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45.CrossRefGoogle Scholar
  9. 9.
    Inman WH. Attitudes to adverse drug reaction reporting. Br J Clin Pharmacol. 1996;41(5):434–5.PubMedGoogle Scholar
  10. 10.
    Hazell L, Shakir SAW. Under-reporting of adverse drug reactions: a systematic review. Drug Saf. 2006;29(5):385–96.CrossRefGoogle Scholar
  11. 11.
    Medrano-Casique N, Tong HY, Borobia AM, et al. Non-chemotherapy-induced agranulocytosis detected by a prospective pharmacovigilance program in a tertiary hospital. Basic Clin Pharmacol Toxicol. 2015;117(6):399–408.CrossRefGoogle Scholar
  12. 12.
    Ibáñez L, Vidal X, Ballarín E, et al. Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol. 2005;60(11):821–9.CrossRefGoogle Scholar
  13. 13.
    Hedenmalm K, Spigset O. Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol. 2002;58(4):265–74.CrossRefGoogle Scholar
  14. 14.
    Spanish Medicines and Medical Devices Agency (AEMPS). Ministry of Health, Consumption and Social Welfare of Spain. Metamizol y riesgo de agranulocitosis [Metamizol and risk of agranulocytosis]. 2018 Oct 30 [cited 2018 Dec 28]. https://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2018/NI_MUH_FV-15-2018-metamizol-agranulocitosis.htm.
  15. 15.
    Andrès E, Mourot-Cottet R, Maloisel F, et al. Idiosyncratic drug-induced neutropenia and agranulocytosis. QJM. 2017;110(5):200–305.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pharmacy DepartmentHospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)MadridSpain
  2. 2.Haematology DepartmentHospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM)MadridSpain

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