Skip to main content
SpringerLink
Log in

Medication Noncompliance and its Implications in Transplant Recipients

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Fig. 1
Fig. 2
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Halloran PF. Immunosuppressive drags for kidney transplantation. N Engl J Med 2004 Dec 23; 351(26): 2715–29

    Article  PubMed  CAS  Google Scholar 

  2. Gaston RS. Maintenance immunosuppression in the renal transplant recipient: an overview. Am J Kidney Dis 2001; 38(S6): S25–35

    Article  PubMed  CAS  Google Scholar 

  3. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353(5): 487–97

    Article  PubMed  CAS  Google Scholar 

  4. Kraeger KP, Berger BA, Felkey B. Medication adherence and persistence: a comprehensive review. Adv Ther 2005 Jul–Aug; 22(4): 313–56

    Article  Google Scholar 

  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, 1997

    Google Scholar 

  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): 1147–52

    Article  PubMed  Google Scholar 

  7. Greenstein S, Siegal B. Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study. Transplantation 1998; 66: 1718–26

    Article  PubMed  CAS  Google Scholar 

  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: 46–54

    PubMed  CAS  Google Scholar 

  9. Raiz LR, Kilty KM, Henry ML, et al. Medication compliance following renal transplantation. Transplantation 1999; 68: 51–5

    Article  PubMed  CAS  Google Scholar 

  10. Gaston RS, Hudson SL, Ward M, et al. Late renal allograft loss: noncompliance masquerading as chronic rejection. Transplant Proc 1999; 31: S21–3

    Article  Google Scholar 

  11. Nevins TE, Kruse L, Skeans MA, et al. The natural history of azathioprine compliance after renal transplantation. Kidney Int 2001; 60: 1565

    Article  PubMed  CAS  Google Scholar 

  12. Hilbrands LB, Hoitsma AJ, Koene RA. Medication compliance after renal transplantation. Transplantation 1995; 60: 914–20

    PubMed  CAS  Google Scholar 

  13. Chisholm MA, Vollenweider LJ, Mulloy LL, et al. Renal transplant patient compliance with free immunosuppressive medications. Transplantation 2000; 70: 1240–4

    Article  PubMed  CAS  Google Scholar 

  14. Loghman-Adham M. Medication noncompliance in patients with chronic disease: issues in dialysis and renal transplantation. Am J Manag Care 2003; 9: 155

    PubMed  Google Scholar 

  15. Kiley DJ, Lam CS, Pollak R. A study of treatment compliance following kidney transplantation. Transplantation 1993; 55: 51–6

    Article  PubMed  CAS  Google Scholar 

  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: 1509–13

    Google Scholar 

  17. Shaw RJ, Palmer L, Blasey C, et al. A typology of non-adherence in pediatric renal transplant recipients. Pediatr Transplantation 2003; 7: 489–93

    Article  Google Scholar 

  18. Laederach-Hofmann K, Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry 2000; 22(6): 412–24

    Article  PubMed  CAS  Google Scholar 

  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): 367–71

    Article  PubMed  Google Scholar 

  20. Nevins TE. Non-compliance and its management in teenagers. Pediatr Transplant 2002; 6: 475–9

    Article  PubMed  Google Scholar 

  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: 1094–7

    Article  PubMed  CAS  Google Scholar 

  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: 769

    Article  PubMed  Google Scholar 

  23. Chapman JR. Compliance: the patient, the doctor, and the medication? Transplantation 2004; 77(5): 782–6

    Article  PubMed  Google Scholar 

  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: 2044–7

    Article  PubMed  CAS  Google Scholar 

  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): 1588–95

    Article  PubMed  Google Scholar 

  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: 631–45

    PubMed  CAS  Google Scholar 

  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: 854

    PubMed  Google Scholar 

  28. Shemesh E, Shneider BL, Savitzky JK, et al. Medication adherence in pediatric and adolescent liver transplant recipients. Pediatrics 2004 Apr; 113(4): 825–32

    Article  PubMed  Google Scholar 

  29. Shemesh E. Nonadherence to medications following pediatric liver transplantation. Pediatr Transplantation 2004; 6: 600–5

    Article  Google Scholar 

  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: E29

    Article  PubMed  CAS  Google Scholar 

  31. Sweet SC, Wong H-H, Webber SA, et al. Pediatric transplantation in the United States, 1995–2004. Am J Transplant 2006; 6: 1132–52

    Article  PubMed  CAS  Google Scholar 

  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: 381–90

    Article  PubMed  Google Scholar 

  33. Kalb LM, Loeber R. Child disobedience and noncompliance: a review. Pediatrics 2003; 111: 641–52

    Article  PubMed  Google Scholar 

  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): 1096–103

    Article  Google Scholar 

  35. Rosenow EC. Patients’ understanding of and compliance with medications: the sixth vital sign? Mayo Clin Proc 2005; 80(8): 983–7

    Article  PubMed  Google Scholar 

  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): 3144–9

    Article  PubMed  Google Scholar 

  37. Chisholm MA. Enhancing transplant patients’ adherence to medication therapy. Clin Transplant 2002; 16(1): 30–18

    Article  PubMed  Google Scholar 

  38. Steiner R. Medication noncompliance: implications for transplant professionals [online]. Available from URL: http://www.medscape.com/viewprogram/3639 [Accessed 2006 May 5]

  39. Aardex. MEMs [online]. Available from URL: http://www.aardex.ch/aardex/index.htm [Accessed 2006 May 23]

  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: 1–14

    Article  PubMed  CAS  Google Scholar 

  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): 786–9

    Article  PubMed  Google Scholar 

  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: 875–82

    Article  PubMed  Google Scholar 

  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): 787–93

    Article  PubMed  CAS  Google Scholar 

  44. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 1999; 23(8): 1296–310

    Article  Google Scholar 

  45. Urquart J. Patient non-compliance with drug regimens: measurement, clinical correlates, economic impact. Eur Heart J 1996; 17 Suppl. A: 8–15

    Article  Google Scholar 

  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): 330–6

    Article  PubMed  CAS  Google Scholar 

  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: 1881–4

    Article  PubMed  CAS  Google Scholar 

  48. Bennett WM, Lindsley J, Buss WC. The effects of age and dosage route on experimental cyclosporine nephrotoxicity. Transplantation 1991; 51: 730–1

    Article  PubMed  CAS  Google Scholar 

  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: 621–5

    Article  PubMed  CAS  Google Scholar 

  50. First MR, Fitzsimmons WE. New drugs to improve transplant outcomes. Transplantation 2004; 77(9 S): S88–92

    Article  PubMed  Google Scholar 

  51. Schubert M, Venkataramanan R, Holt DW, et al. Pharmacokinetics of sirolimus and tacrolimus in pediatric transplant patients. Am J Transplant 2004; 4: 767–73

    Article  PubMed  CAS  Google Scholar 

  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): 13–21

    Article  PubMed  CAS  Google Scholar 

  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): 505–15

    Article  PubMed  Google Scholar 

  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): 1233–43

    Article  PubMed  CAS  Google Scholar 

  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): 657–65

    PubMed  Google Scholar 

  56. Roter DL, Hall JA, Merisca R, et al. Effectiveness of interventions to improve patient compliance: a meta-analysis. Med Care 1998; 36(8): 1138–1161

    Article  PubMed  CAS  Google Scholar 

  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: 467–71

    PubMed  CAS  Google Scholar 

  58. Nevins TE, Matas AJ. Medication noncompliance: another iceberg’s tip. Transplantation 2004 Mar 15; 77(5): 776–8

    Article  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Division of Organ Transplantation, Brown Medical School, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island, 02903, USA

    Paul E. Morrissey

  2. University of Rhode Island, Kingston, Rhode Island, USA

    Michelle L. Flynn & Sonia Lin

Authors
  1. Paul E. Morrissey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michelle L. Flynn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sonia Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul E. Morrissey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morrissey, P.E., Flynn, M.L. & Lin, S. Medication Noncompliance and its Implications in Transplant Recipients. Drugs 67, 1463–1481 (2007). https://doi.org/10.2165/00003495-200767100-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200767100-00007

Keywords

Search

Navigation