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Compliance issues in transplant patients


John Sexton
MSc BPharm(Hons) MCPP MRPharmS
Principal Pharmacist Lecturer–Practitioner
The Royal Liverpool and Broadgreen University Hospitals NHS Trust and Liverpool John Moores University

Health professionals use the terms compliance and adherence to define the extent to which a patient takes their prescribed medicines as directed. The problem is common, but our understanding of its extent is frustrated by two factors.

First, compliance is notoriously difficult to measure. Various strategies have been described in the literature, including the use of patient diaries, tablet counts, therapeutic drug-level monitoring, electronic recording devices and the like, but the determined patient can fool all of these. For example, a patient may take their drugs only before an expected outpatient clinic to ensure an adequate blood level on sampling.

The second factor making it difficult to classify noncompliance is that there is not a standard definition. Absolute noncompliance can be defined, but much more common is the partial or “subclinical” noncompliance that is exhibited by a substantial minority of transplant recipients, which could include erratic dosing intervals, missed doses and divergence from the agreed doses. Is a patient noncompliant if they miss one dose a week, or five, or ten, or if they take their medicines more than an hour late, or two, or six?

Reasons for noncompliance
Even with the best of intentions, a patient may fail to take their medicines as the doctor intended, but it seems likely that patients will be less likely to take medicines if:

  • They cannot see or feel an immediate benefit from doing so.
  • They cannot see or feel an immediate harm from not doing so.
  • The medicines have a variety of unpleasant effects and/or the information provided about them warns of potential serious complications from their use.
  • They will be taking these medicines for a prolonged period.
  • They will be taking several medicines at the same time.

Since all of the above apply to transplant medication recipients, noncompliance is unsurprising. Non-compliance with medication following renal transplantation, for example, has been reported as between 5 and 43%, the wide range quoted being due to the different ways noncompliance is defined and assessed, as detailed above.(1) The term concordance is coming into vogue to describe the level of agreement between a patient and the prescriber on the need for and delivery of a therapeutic intervention. A patient and prescriber may have different views on their medication, and if they do, the views of the patient may take precedence, leading to noncompliance.(2)

Successful organ transplantation also depends on compliance with factors other than medication: diet, cancer screening, clinic attendance, blood pressure monitoring, smoking cessation, rapid reporting of problems and so forth. The literature suggests that patients are often noncompliant in a variety of ways, and as a result it may be possible to predict those patients more likely to fail to comply, as shown in Table 1. Other studies, however, have failed to identify any significant predictive factors.

Consequences of noncompliance and solutions
Despite the difficulties in measuring and categorising compliance, there is a wealth of literature associating noncompliance after organ transplantation with rejection episodes, loss of confidence in effective therapies, graft loss, morbidity and mortality. For example, up to a quarter of lost kidneys and deaths after the initial transplant period can be ascribed to noncompliance.(3,5) Strategies that may be effective in improving compliance are listed below, though few have proven general efficacy.

Careful selection of patients for transplant
Given that there are usually more potential recipients than donor organs, it seems reasonable to question the future compliance of patients with psychosocial risk factors for noncompliance, especially if they have a history of failure to follow lifestyle advice, missing appointments or substance abuse.

Psychosocial strategies
There are a lack of hard data on whether simplifying regimens as much as possible and counselling or educational sessions will improve compliance after transplant. Nevertheless, it would seem prudent to take all opportunities to educate patients about their medication and the need to comply with it, and the possible adverse consequences of failing to do so.

Compliance aids
There is a high level of trust among some professionals in disposable or refillable monitored dosing systems. A substantial workload is generated in filling them, however, the stability of the medication may be affected, and they can adversely affect patients’ ability to recall names and doses. On the other hand, “compliance charts” that relate medication use to mealtimes have been shown to be effective in improving comprehension and compliance.(5)

Promoting concordance
It would seem reasonable that we listen to the patients themselves. They may identify problems in obtaining their medication, articulate fears or report side-effects such as weight gain from steroids or diarrhoea from mycophenolate. Compliance may be improved if prescribers encourage and act on this sort of information to agree a treatment plan with their patient.

Noncompliance is a major cause of morbidity and mortality after solid organ transplantation, but much remains unknown regarding its true aetiology and how it may be overcome. However, pharmacists can act to promote concordance and compliance, and the most appropriate action will generally become clear only after the patient has been encouraged to honestly and accurately state their beliefs and current practice.


  1. Vasquez EM, Tanzi M, Bednedetti E, Pollack R. Medication noncompliance after kidney transplantation. Am J Health-Syst Pharm 2003;60:266-9.
  2. Marinker M, Shaw J. Not to be taken as directed. BMJ 2003;326:348-9.
  3. Bunzel B, Laederach-Hofmann K. Solid-organ transplantation: are there predictive factors for post- transplantation non-compliance? A literature overview. Transplantation 2000;70:711-6.
  4. Riaz LR, Kilty KM, Henry ML, Ferguson RM. Medication compliance following renal transplantation. Transplantation 1999:68:51-5.
  5. Loghman-Adham M. Medication non-compliance in patients with chronic disease: Issues in dialysis and renal transplantation. Am J Manage Care 2003;9:155-71.

The Edinburgh
Renal Unit
The Kidney Patient Guide

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