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Do Women Have More Adverse Drug Reactions?

Abstract

Up to 5% of all hospital admissions are the result of adverse drug reactions (ADRs). Identifying those factors which may predispose to ADRs is essential for risk management. Amongst the known risk factors for adverse reactions are increasing age, polypharmacy, liver and renal disease as well as being female. Female patients have a 1.5- to 1.7-fold greater risk of developing an ADR, including adverse skin reactions, compared with male patients. The reasons for this increased risk are not entirely clear but include gender-related differences in pharmacokinetic, immunological and hormonal factors as well as differences in the use of medications by women compared with men.

Women generally have a lower lean body mass, a reduced hepatic clearance, have differences in activity of cytochrome P450 (CYP) enzymes (40% increase in CYP3A4, varied decrease in CYP2D6, CYP2C19 and CYP1A2), and metabolize drugs at different rates compared with men. Other important factors include conjugation, absorption, protein binding and renal elimination, which may all have some gender-based differences. However, how these differences result in an increased risk of ADRs is not clear.

There are pharmacodynamic differences between men and women, seen particularly with cardiac and psychotropic medications. There is no doubt that chlorpromazine, fluspirilene and various antipsychotics appear more effective in women than men for the same dosage and plasma concentration. Similarly, women are at increased risk of QT prolongation with certain anti-arrhythmic drugs compared with men even at equivalent serum concentrations. The mechanisms are unknown.

Increasingly the evidence is that idiosyncratic drug reactions, particularly cutaneous reactions, appear to have an immunological etiology. It is possible that gender difference in T cell activation and proliferation account for this as well as the increased prevalence of skin diseases such as systemic lupus erythematosus and photosensitivity. Whatever the mechanism(s), it is important to be aware that gender is a significant factor in ADRs.

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References

  1. 1.

    Executive summary of disease management of drug hypersensitivity: a practice parameter. Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1999; 83: 665-700

  2. 2.

    Leape L.L., Brennan T.A., Laird N., et al. The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324: 377–384

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Thomas E.J., Studdert D.M., Burstin H.R., et al. Incidence and types of adverse events and negligent care in Utah and Colorado. Med Care 2000; 38: 261–271

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Classen D.C., Pestotnik S.L., Evans R.S., et al. Adverse drug events in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277: 301–306

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Lazarou J., Pomeranz B.H., Corey P.N. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998; 279: 1200–1205

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Miller R.R. Hospital admissions due to adverse drug reactions. A report from the Boston Collaborative Drug Surveillance Program. Arch Intern Med 1974; 134: 219–223

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Pouyanne P., Haramburu F., Imbs J.L., et al. Admissions to hospital caused by adverse drug reactions: cross sectional incidence study. BMJ 2000; 320: 1036

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Fattinger K., Roos M., Vergeres P., et al. Epidemiology of drug exposure and adverse drug reactions in two Swiss departments of internal medicine. Br J Clin Pharmacol 2000; 49: 158–167

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Martin R.M., Biswas P.N., Freemantle S.N., et al. Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol 1998; 46: 505–511

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    van der Klauw M.M., Wilson J.H., Stricker B.H. Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974–1994). Am J Hematol 1998; 57: 206–211

    PubMed  Article  Google Scholar 

  11. 11.

    van der Klauw M.M., Wilson J.H., Stricker B.H. Drug-associated anaphylaxis: 20 years of reporting in The Netherlands (1974–1994) and review of the literature. Clin Exp Allergy 1996; 26: 1355–1363

    PubMed  Article  Google Scholar 

  12. 12.

    Figueras A., Capella D., Castel J.M., et al. Spontaneous reporting of adverse drug reactions to non-steroidal anti-inflammatory drugs. A report from the Spanish System of Pharmacovigilance, including an early analysis of topical and entericcoated formulations. Eur J Clin Pharmacol 1994; 47: 297–303

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Makkar R.R., Fromm B.S., Steinman R.T., et al. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993; 270: 2590–2597

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Tran C., Knowles S.R., Liu B.A., et al. Gender differences in adverse drug reactions. J Clin Pharmacol 1998; 38: 1003–1009

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Domecq C., Naranjo C.A., Ruiz I., et al. Sex-related variations in the frequency and characteristics of adverse drug reactions. Int J Clin Pharmacol Ther Toxicol 1980; 18: 362–366

    PubMed  CAS  Google Scholar 

  16. 16.

    Naldi L., Conforti A., Venegoni M., et al. Cutaneous reactions to drugs: an analysis of spontaneous reports in four Italian regions. Br J Clin Pharmacol 1999; 48: 839–846

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Kando J.C., Yonkers K.A., Cole J.O. Gender as a risk factor for adverse events to medications. Drugs 1995; 50: 1–6

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Harris R.Z., Benet L.Z., Schwartz J.B. Gender effects in pharmacokinetics and pharmacodynamics. Drugs 1995; 50: 222–239

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Ochs H.R., Greenblatt D.J., Divoll M., et al. Diazepam kinetics in relation to age and sex. Pharmacology 1981; 23: 24–30

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Wrighton S.A., Stevens J.C. The human hepatic cytochromes P450 involved in drug metabolism. Crit Rev Toxicol 1992; 22: 1–21

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Hunt C.M., Westerkam W.R., Stave G.M. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 1992; 44: 275–283

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Schmucker D.L., Woodhouse K.W., Wang R.K., et al. Effects of age and gender on in vitro properties of human liver microsomal monooxygenases. Clin Pharmacol Ther 1990; 48: 365–374

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Divoll M., Greenblatt D.J., Harmatz J.S., et al. Effect of age and gender on disposition of temazepam. J Pharm Sci 1981; 70: 1104–1107

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Benton R.E., Sale M., Flockhart D.A., et al. Greater quinidine-induced QTc interval prolongation in women. Clin Pharmacol Ther 2000; 67: 413–418

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Yonkers K.A., Kando J.C., Cole J.O., et al. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry 1992; 149: 587–595

    PubMed  CAS  Google Scholar 

  26. 26.

    Naisbitt D.J., Gordon S.F., Pirmohamed M., et al. Immunological principles of adverse drug reactions: the initiation and propagation of immune responses elicited by drug treatment. Drug Saf 2000; 23: 483–507

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Park B.K., Kitteringham N.R., Powell H., Pirmohamed M. Advances in molecular toxicology-towards understanding idiosyncratic drug toxicity. Toxicology 2000; 153: 39–60

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Yawalkar N., Hari Y., Frutig K., et al. T cells isolated from positive epicutaneous test reactions to amoxicillin and ceftriaxone are drug specific and cytotoxic. J Invest Dermatol 2000; 115: 647–652

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Yawalkar N., Egli F., Hari Y., et al. Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions. Exp Allergy 2000; 30: 847–855

    Article  CAS  Google Scholar 

  30. 30.

    Borda I., Jick H., Slone D., et al. Studies of drug usage in five Boston hospitals. JAMA 1967; 202: 506–510

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Svarstad B.L., Cleary P.D., Mechanic D., et al. Gender differences in the acquisition of prescribed drugs: an epidemiological study. Med Care 1987; 25: 1089–1098

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Sihvo S., Klaukka T., Martikainen J., et al. Frequency of daily over-the-counter drug use and potential clinically significant over-the-counter-prescription drug interactions in the Finnish adult population. Eur J Clin Pharmacol 2000; 56: 495–499

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Al-Windi A., Elmfeldt D., Svardsudd K. The relationship between age, gender, wellbeing and symptoms, and the use of pharmaceuticals, herbal medicines and selfcare products in a Swedish municipality. Eur J Clin Pharmacol 2000; 56: 311–317

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Marius Rademaker.

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Rademaker, M. Do Women Have More Adverse Drug Reactions?. Am J Clin Dermatol 2, 349–351 (2001). https://doi.org/10.2165/00128071-200102060-00001

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Keywords

  • Systemic Lupus Erythematosus
  • Adverse Drug Reaction
  • Lichen Planus
  • Hepatic Clearance
  • Dipyrone