Drugs

, Volume 67, Issue 10, pp 1463–1481 | Cite as

Medication Noncompliance and its Implications in Transplant Recipients

  • Paul E. Morrissey
  • Michelle L. Flynn
  • Sonia Lin
Review Article

Abstract

The transplant patient’s therapeutic regimen consists of a lifelong drug therapy, including immunosuppressive drugs, prophylactic antimicrobials and often medications for the treatment of hypertension, diabetes mellitus and other comorbid diseases. Regular clinic appointments are required to monitor for signs and symptoms of immunological injury, recurrent disease and adverse drug effects. Patients are instructed to avoid risk factors for cardiovascular disease and cancer (e.g. diet, exercise, sun protection and not smoking). Noncompliance with all aspects of this regimen is substantial. Medication noncompliance leads to an increased incidence of acute rejection, chronic rejection and graft loss. Undoubtedly, many practitioners fail to appreciate the extent of noncompliance as the signs are often subtle and most patients are unwilling to disclose deliberate or widespread disregard for medication use. Newer immunosuppressive agents, particularly once-daily medications and long-acting antibody preparations offer convenience and monitoring that may improve compliance. This review focuses on the prevalence, correlates and consequences of medication nonadherence after organ transplantation. Current recommendations to enhance adherence are discussed.

Keywords

Tacrolimus Transplant Recipient Medication Adherence Acute Rejection Graft Loss 

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Halloran PF. Immunosuppressive drags for kidney transplantation. N Engl J Med 2004 Dec 23; 351(26): 2715–29PubMedCrossRefGoogle Scholar
  2. 2.
    Gaston RS. Maintenance immunosuppression in the renal transplant recipient: an overview. Am J Kidney Dis 2001; 38(S6): S25–35PubMedCrossRefGoogle Scholar
  3. 3.
    Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353(5): 487–97PubMedCrossRefGoogle Scholar
  4. 4.
    Kraeger KP, Berger BA, Felkey B. Medication adherence and persistence: a comprehensive review. Adv Ther 2005 Jul–Aug; 22(4): 313–56CrossRefGoogle Scholar
  5. 5.
    Marinker M, Blenkinsopp A, Bond C, et al., editors. From compliance to concordance: achieving shared goals in medicine taking. London: Royal Pharmaceutical Society of Great Britain, 1997Google Scholar
  6. 6.
    Chapman RH, Benner JS, Petrilla AA, et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med 2005 May 23; 165(10): 1147–52PubMedCrossRefGoogle Scholar
  7. 7.
    Greenstein S, Siegal B. Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study. Transplantation 1998; 66: 1718–26PubMedCrossRefGoogle Scholar
  8. 8.
    Siegal BR, Greenstein SM. Postrenal transplant compliance from the perspective of African-Americans, Hispanic-Americans, and Anglo-Americans. Adv Ren Replace Ther 1997; 4: 46–54PubMedGoogle Scholar
  9. 9.
    Raiz LR, Kilty KM, Henry ML, et al. Medication compliance following renal transplantation. Transplantation 1999; 68: 51–5PubMedCrossRefGoogle Scholar
  10. 10.
    Gaston RS, Hudson SL, Ward M, et al. Late renal allograft loss: noncompliance masquerading as chronic rejection. Transplant Proc 1999; 31: S21–3CrossRefGoogle Scholar
  11. 11.
    Nevins TE, Kruse L, Skeans MA, et al. The natural history of azathioprine compliance after renal transplantation. Kidney Int 2001; 60: 1565PubMedCrossRefGoogle Scholar
  12. 12.
    Hilbrands LB, Hoitsma AJ, Koene RA. Medication compliance after renal transplantation. Transplantation 1995; 60: 914–20PubMedGoogle Scholar
  13. 13.
    Chisholm MA, Vollenweider LJ, Mulloy LL, et al. Renal transplant patient compliance with free immunosuppressive medications. Transplantation 2000; 70: 1240–4PubMedCrossRefGoogle Scholar
  14. 14.
    Loghman-Adham M. Medication noncompliance in patients with chronic disease: issues in dialysis and renal transplantation. Am J Manag Care 2003; 9: 155PubMedGoogle Scholar
  15. 15.
    Kiley DJ, Lam CS, Pollak R. A study of treatment compliance following kidney transplantation. Transplantation 1993; 55: 51–6PubMedCrossRefGoogle Scholar
  16. 16.
    Vlaminck H, Maes B, Evers G, et al. Prospective study on late consequences of subclinical non-compliance with immunosuppressive therapy in renal transplant patients. Transplantation 2004; 4: 1509–13Google Scholar
  17. 17.
    Shaw RJ, Palmer L, Blasey C, et al. A typology of non-adherence in pediatric renal transplant recipients. Pediatr Transplantation 2003; 7: 489–93CrossRefGoogle Scholar
  18. 18.
    Laederach-Hofmann K, Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry 2000; 22(6): 412–24PubMedCrossRefGoogle Scholar
  19. 19.
    Jarzembowski T, John E, Panaro F, et al. Impact of non-compliance on outcome after pediatric kidney transplantation: an analysis in racial subgroups. Pediatr Transplant 2004 Aug; 8(4): 367–71PubMedCrossRefGoogle Scholar
  20. 20.
    Nevins TE. Non-compliance and its management in teenagers. Pediatr Transplant 2002; 6: 475–9PubMedCrossRefGoogle Scholar
  21. 21.
    Beck DE, Fennell RS, Yost RL, et al. Evaluation of an educational program on compliance with medication regimens in pediatric patients with renal transplants. J Pediatr 1980; 96: 1094–7PubMedCrossRefGoogle Scholar
  22. 22.
    Butler JA, Roderick P, Mason JC, et al. Frequency and impact of nonadherence to immunosuppressant following renal transplantation: a systematic review. Transplantation 2004; 77: 769PubMedCrossRefGoogle Scholar
  23. 23.
    Chapman JR. Compliance: the patient, the doctor, and the medication? Transplantation 2004; 77(5): 782–6PubMedCrossRefGoogle Scholar
  24. 24.
    Morrissey PE, Reinert S, Gohh R, et al. Factors contributing to acute rejection in renal transplantation: the role of noncompliance. Transplant Proc 2005; 37: 2044–7PubMedCrossRefGoogle Scholar
  25. 25.
    Dobbels F, Vanhaecke J, Desmyttere A, et al. Prevalence and correlates of self-reported pretransplant nonadherence with medication in heart, liver, and lung transplant candidates. Transplantation 2005 Jun 15; 79(11): 1588–95PubMedCrossRefGoogle Scholar
  26. 26.
    Dew MA, Roth LH, Thompson ME, et al. Medical compliance and its predictors in the first year after heart transplantation. J Heart Lung Transplant 1996; 15: 631–45PubMedGoogle Scholar
  27. 27.
    De Geest S, Abraham I, Moons P, et al. Late acute rejection and subclinical noncompliance with cyclosporine therapy in heart transplant recipients. J Heart Lung Transplant 1998; 17: 854PubMedGoogle Scholar
  28. 28.
    Shemesh E, Shneider BL, Savitzky JK, et al. Medication adherence in pediatric and adolescent liver transplant recipients. Pediatrics 2004 Apr; 113(4): 825–32PubMedCrossRefGoogle Scholar
  29. 29.
    Shemesh E. Nonadherence to medications following pediatric liver transplantation. Pediatr Transplantation 2004; 6: 600–5CrossRefGoogle Scholar
  30. 30.
    Shemesh E, Lurie S, Stuber ML, et al. A pilot study of posttraumatic stress and nonadherence in pediatric liver transplant recipients. Pediatrics 2000; 105: E29PubMedCrossRefGoogle Scholar
  31. 31.
    Sweet SC, Wong H-H, Webber SA, et al. Pediatric transplantation in the United States, 1995–2004. Am J Transplant 2006; 6: 1132–52PubMedCrossRefGoogle Scholar
  32. 32.
    Dobbels F, Van Damme-Lombaert R, Vanhaecke J, et al. Growing pains: nonadherence with the immunosuppressive regimen in adolescent transplant recipients. Pediatr Transplant 2005; 9: 381–90PubMedCrossRefGoogle Scholar
  33. 33.
    Kalb LM, Loeber R. Child disobedience and noncompliance: a review. Pediatrics 2003; 111: 641–52PubMedCrossRefGoogle Scholar
  34. 34.
    Schneider J, Kaplan SH, Greenfield S, et al. Better physician-patient relationships are associated with higher reported adherence to antiretroviral therapy in patients with HIV infection. J Gen Int Med 2004; 19(11): 1096–103CrossRefGoogle Scholar
  35. 35.
    Rosenow EC. Patients’ understanding of and compliance with medications: the sixth vital sign? Mayo Clin Proc 2005; 80(8): 983–7PubMedCrossRefGoogle Scholar
  36. 36.
    Butler JA, Peveler RC, Roderick P, et al. Modifiable risk factors for non-adherence to immunosuppressants in renal transplant recipients: a cross-sectional study. Nephrol Dial Transplant 2004; 19(12): 3144–9PubMedCrossRefGoogle Scholar
  37. 37.
    Chisholm MA. Enhancing transplant patients’ adherence to medication therapy. Clin Transplant 2002; 16(1): 30–18PubMedCrossRefGoogle Scholar
  38. 38.
    Steiner R. Medication noncompliance: implications for transplant professionals [online]. Available from URL: http://www.medscape.com/viewprogram/3639 [Accessed 2006 May 5]
  39. 39.
    Aardex. MEMs [online]. Available from URL: http://www.aardex.ch/aardex/index.htm [Accessed 2006 May 23]
  40. 40.
    Feldman HI, Hackett M, Bilker W, et al. Potential utility of electronic drug compliance monitoring in measures of adverse outcomes associated with immunosuppressive agents. Pharmacoepidemiol Drug Saf 1999; 8: 1–14PubMedCrossRefGoogle Scholar
  41. 41.
    Butler JA, Peveler RC, Roderick P, et al. Measuring compliance with drug regimens after renal transplantation: comparison of self-report and clinician rating with electronic monitoring. Transplantation 2004 Mar 15; 77(5): 786–9PubMedCrossRefGoogle Scholar
  42. 42.
    Andrade AS, McGruder HF, Wu AW, et al. A programmable prompting device improves adherence to highly active antiretroviral therapy in HIV-infected subjects with memory impairment. Clin Infect Dis 2005; 41: 875–82PubMedCrossRefGoogle Scholar
  43. 43.
    Safren SA, Hendriksen ES, Desousa N, et al. Use of an on-line pager system to increase adherence to antiretroviral medications. AIDS Care 2003; 15(6): 787–93PubMedCrossRefGoogle Scholar
  44. 44.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 1999; 23(8): 1296–310CrossRefGoogle Scholar
  45. 45.
    Urquart J. Patient non-compliance with drug regimens: measurement, clinical correlates, economic impact. Eur Heart J 1996; 17 Suppl. A: 8–15CrossRefGoogle Scholar
  46. 46.
    Chisholm MA, Mulloy LL, Jagadeesan M, et al. Impact of clinical pharmacy services on renal transplant patients’ compliance with immunosuppressive medications. Clin Transplant 2001; 15(5): 330–6PubMedCrossRefGoogle Scholar
  47. 47.
    Eisen SA, Miller DK, Woodward RS, et al. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med 1990; 150: 1881–4PubMedCrossRefGoogle Scholar
  48. 48.
    Bennett WM, Lindsley J, Buss WC. The effects of age and dosage route on experimental cyclosporine nephrotoxicity. Transplantation 1991; 51: 730–1PubMedCrossRefGoogle Scholar
  49. 49.
    Hardinger KL, Park JM, Schnitzler MA, et al. Pharmacokinetics of tacrolimus in kidney transplant recipients: daily versus once daily dosing. Am J Transplant 2004; 4: 621–5PubMedCrossRefGoogle Scholar
  50. 50.
    First MR, Fitzsimmons WE. New drugs to improve transplant outcomes. Transplantation 2004; 77(9 S): S88–92PubMedCrossRefGoogle Scholar
  51. 51.
    Schubert M, Venkataramanan R, Holt DW, et al. Pharmacokinetics of sirolimus and tacrolimus in pediatric transplant patients. Am J Transplant 2004; 4: 767–73PubMedCrossRefGoogle Scholar
  52. 52.
    Sarwal MM, Yorgin PD, Alexander S, et al. Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation. Transplantation 2001 Jul 15; 72(1): 13–21PubMedCrossRefGoogle Scholar
  53. 53.
    Shapiro R, Basu A, Tan H, et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with thymoglobulin or campath. J Am Coll Surg 2005 Apr; 200(4): 505–15PubMedCrossRefGoogle Scholar
  54. 54.
    Caillard S, Dharnidharka V, Agodoa L, et al. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 2005; 80(9): 1233–43PubMedCrossRefGoogle Scholar
  55. 55.
    Peterson AM, Takiya L, Finley R. Meta-analysis of trials of interventions to improve medication adherence. Am J Health Syst Pharm 2003; 60(7): 657–65PubMedGoogle Scholar
  56. 56.
    Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care 1998; 36(8): 1138–1161PubMedCrossRefGoogle Scholar
  57. 57.
    Troppmann C, Benedetti E, Gruessner RWG, et al. Retransplantation after renal allograft loss due to noncompliance: indications, outcome, and ethical concerns. Transplantation 1995; 59: 467–71PubMedGoogle Scholar
  58. 58.
    Nevins TE, Matas AJ. Medication noncompliance: another iceberg’s tip. Transplantation 2004 Mar 15; 77(5): 776–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Paul E. Morrissey
    • 1
  • Michelle L. Flynn
    • 2
  • Sonia Lin
    • 2
  1. 1.Division of Organ Transplantation, Brown Medical SchoolRhode Island HospitalProvidenceUSA
  2. 2.University of Rhode IslandKingstonUSA

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