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Pharmacy Practice News – Medication Adherence in Solid Organ Transplant Recipients

ISSUE: MAY 2014 | VOLUME: 41

Seth Heldenbrand, PharmD Clinical Pharmacy Specialist, Solid Organ Transplant Associate Professor College of Pharmacy Department of Pharmacy Practice University of Arkansas for Medical Sciences Little Rock, Arkansas

The International Society for Pharmacoeconomics and Outcomes Research defines medication adherence as the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen. Depending on how it is calculated, nonadherence to medications can account for nearly 70% of medication-related hospital admissions and approximately $100 billion to $300 billion in health care costs annually.

Medication nonadherence following solid organ transplantation can lead to acute rejection, graft loss, infections, additional morbidity and even death. The gravity of this issue has not been lost on transplant pharmacists, who, in controlled trials, have been shown to improve both medication adherence and certain transplant-related outcomes.1

Causes of Nonadherence

Medication nonadherence can be broadly categorized as intentional or unintentional. Intentional nonadherence involves the patient making a conscious choice not to take a medication as prescribed. Patients demonstrate intentional nonadherence for a variety of reasons including their financial situation, social pressures, adverse effects of the drugs and a lack of perceived benefits of therapy.

Conversely, unintentional nonadherence occurs when a patient plans to take a medicine as instructed but fails to do so for some reason (eg, carelessness, forgetfulness, poor planning, etc). Although this view is somewhat simplistic, it highlights the need for tools and strategies to help the patient struggling with medication adherence.

Monitoring medication adherence is an important component of patient care after a solid organ transplant. Several methods, such as patient self-reporting, manual pill counts, prescription refill records, electronic pill bottle adherence technologies, laboratory monitoring, and emerging biologic dose administration recording devices, can help clinicians monitor adherence. Newer technologies under development rely on microtransmitters to confirm pill ingestion and adherence by sending data wirelessly to a remote monitor.

However, each method of monitoring adherence has limitations. For example, the accuracy of patient self-reporting hinges on the patient’s memory and honesty. Patients forgetting their pill bottles or “pill dumping” before the evaluation can compromise manual pill counts. Invasive blood monitoring guarantees ingestion but not adherence. Because all methods to monitor medication adherence have their drawbacks, most experts recommend using more than one tool simultaneously to achieve best results.

Traditional Tools To Improve Adherence

Most methods to improve medication adherence focus on changing the patient’s medication-taking behavior. Changing behavior typically requires modifying a patient’s beliefs about the medication regimen. For example, a patient is much less likely to be adherent if he or she believes that the regimen is too complex, too expensive, or has too many adverse effects. Adherence interventions or the removal of barriers to adherence can be classified as behavioral, educational, or organizational.

Transplant pharmacists have numerous tools that can be employed alone or in combination to improve patient adherence through behavior modification. Methods that have been studied in the transplant setting include counseling, reinforcement, and education. Other methods include dosage reminders, financial mitigation, and simplification of dosages. This can be accomplished by the organ transplant pharmacist working alone or it can be done in concert with a physician.

Traditional medication reminders such as simple alarms, calendar reminders, and daily or weekly pillboxes are commonly used to help transplant patients stay on their drug regimens and are most effective in mitigating unintentional nonadherence, particularly with less complex regimens. However, in most patients, as the complexity of the regimen increases, the effectiveness of these interventions wanes.

Behavioral interventions and medication counseling generally are regarded as reliable methods that have been frequently evaluated and provide the most benefit to patients struggling with nonadherence. In patients taking more than six medications, pharmacist counseling is considered the best method for improving adherence.2

The medication burden for the average transplant recipient is substantial; such a patient typically is discharged from the hospital taking anywhere from 11 to 14 drugs. Therefore, the Centers for Medicare & Medicaid Services (CMS) mandates the involvement of transplant pharmacists in patient education and care.

Common patient education strategies that transplant pharmacists use include traditional education, medication counseling, medication-taking aids such as pillboxes, and detailed regimen instructions.

Other methods include the use of motivational interviewing and emotional intelligence. These techniques focus on identifying with patients and facilitating their intrinsic motivation to help them modify their behaviors. Again, it is best to use these methods in combination to produce a meaningful improvement in medication adherence.

Smartphone Apps And Adherence

Emerging technologies such as smartphone applications that promote medication adherence and that are tailored to a patient’s specific needs have the potential to significantly improve adherence and outcomes.

The prevalence of smartphones has been growing among all demographic groups over the past five years. Applications aimed at medication adherence have shown promise in several small studies, but large-scale trials assessing their true ability to improve adherence are lacking.

Smartphone apps may represent a useful tool for patients demonstrating unintentional nonadherence. In a recent article, Lindsey Dayer, PharmD, BCOP, a clinical pharmacist in palliative care and an assistant professor at the University of Arkansas for Medical Sciences, in Little Rock, and her colleagues wrote: “Adherence apps can be downloaded for little to no cost, and their benefits may be realized by anyone taking prescription medications. However, these apps may prove most beneficial for patients with complex medication regimens or for caregivers … or family members. The growing prevalence of smartphones in the United States and their constant, easy accessibility make adherence apps appealing to many because they cost little and can provide user-specific information.”3

The number of adherence apps available from the various online marketplaces is overwhelming. Dr. Dayer and her colleagues reviewed 160 apps downloadable from iTunes, Android Marketplace and Blackberry App World.3 Functionality varied widely among the available apps, so the authors identified the most desirable features and then scored and ranked the apps by which ones had the highest number of valuable features.

Important app features evaluated by the researchers included the ability to enter medication data online; complex instruction capability; cloud storage of data; HIPAA compliance; tracking of taken and missed doses; and the ability to sync or export data to health care professionals. The ability of a provider to enter the regimen using drop-down boxes and send it to the patient’s device through online data entry can reduce patient input errors and can decrease stress on patients who are not tech savvy. Moreover, the capability to export robust medication administration data is a useful function for providers monitoring adherence rates and helps identify problem areas for patients who are missing doses.

Although some apps handle only simple instructions such as taking a medication once or twice per day, others can facilitate medication tapers, nondaily dosing, and monthly pill holidays that generate accurate reminders and eliminate unnecessary ones.

image Of the apps that were reviewed and tested by Dayer et al, the one with the highest performance was MyMedSchedule (iTunes and Android). MyMedSchedule has a companion website ( that can be used by patients and health care providers. “MedActionPlan … allows providers to quickly create personalized treatment plans for patients that are easy to understand and follow,” Tim Peters, owner of MedActionPlan, LLC, said in an interview with Pharmacy Practice News. “Providers can send this information directly into the patients’ MyMedSchedule, a patient version of MedActionPlan. Getting patients proactive in their health care is an important step in addressing nonadherence.”

Pharmacists have been using MedActionPlan and MyMedSchedule in transplant patients since its introduction in 2004. “MedActionPlan is … the best tool on the market for closing the gap between medication education for transplant recipients and medication reconciliation for transplant health care professionals,” said Pam Maxwell, PharmD, BCPS, a transplant specialist and residency director at University Health-System, in San Antonio. “Its ease of comprehension for extremely complex medication regimens promotes adherence within a diverse patient population, while its user-friendly automation promotes efficiency for providers and engagement in self-care for patients.”

However, these apps have one major limitation, according to Sarah Hutton, PharmD, a transplant pharmacist at Sanford Hospital, in Sioux Falls, South Dakota. The technology “does not communicate with our electronic medical record [EMR],” Dr. Hutton said. “Hence, a provider is still required to do medication reconciliation in the EMR. This results in a lot of duplicate work and introduces risk for transcription errors.”

Other apps that Dayer et al ranked highly were MyMeds ( and MedSimple ( Notably, none of the apps communicated with EMR systems at the time the authors reviewed them—a lack of functionality that persists. Both are available in the iTunes and Android marketplaces.

Other innovative features that are being integrated into newer apps include escalating reminder systems that enlist the help of caregivers using patient-specified social networking to improve adherence. Escalating reminders become more aggressive if the patient neglects to confirm or deny the indicated dose. If all reminders are ignored and the patient has specified a caregiver to contact, the app can alert the caregiver that the patient has missed doses and should be reminded to take the medication.

Medication adherence is a complex problem, especially for transplant recipients who often have a high medication burden and are more likely to suffer immediate as well as long-term consequences of nonadherence. A variety of tried and emerging tools exist for pharmacists and other clinicians to help ensure adherence. Medication adherence apps are exciting technologies aimed at addressing these problems. Clinical evidence on how to best use these technologies to improve medication regimen adherence should be available in the near future.


Alloway RR, Dupuis R, Gabardi S, et al. Evolution of the role of the transplant pharmacist on the multidisciplinary transplant team. Am J Transplant. 2011;11(8):1576-1583. Conn VS, Hafdahl AR, Cooper PS, et al. Interventions to improve medication adherence among older adults: meta-analysis of adherence outcomes among randomized controlled trials. Gerontologist. 2009;49(4):447-462. Dayer L, Heldenbrand SM, Anderson P, et al. Smartphone medication adherence apps: potential benefits to patients and providers. J Am Pharm Assoc. 2013;53:172-181. img-button Series Editor:

Eric M. Tichy, PharmD, BCPS, FCCP Senior Clinical Pharmacy Specialist, Solid Organ Transplantation Director, PGY-2 Residency-Transplant Department of Pharmacy Yale-New Haven Hospital New Haven, CT

Adherence to the post-transplantation medication regimen remains the greatest area in which pharmacy providers and patients can have a defined effect on transplant outcomes. As with other problems in society, there is significant potential for technology to provide a solution to the conundrum of medication nonadherence. The transplant pharmacy community has long been an early adopter of Web- and smartphone-based programs that are designed to provide medication use education and tools to improve patient adherence to the medication regimen.

Although there are more than 160 smartphone applications designed to improve patient adherence to the medication regimen, an informal poll of the American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network recently showed that only one app was pervasively used (MyMedSchedule), with other transplant centers continuing to rely mostly on paper-based systems.

A major limitation of these Web- and smartphone-based programs is the lack of automated coordination with the “official” EMR medication list. Furthermore, these programs do not even coordinate with the outpatient dispensing pharmacy. The lack of electronic coordination between these 3 entities (dispensing pharmacy, provider medical record, and patient) leaves a fragmented process with numerous opportunities for miscommunication and errors that are detrimental to medication use adherence.

The challenge for the producers of smartphone technology is to provide a patient-friendly interface that also serves as a platform that coordinates between the provider medical record and dispensing pharmacy. When those aims are achieved, our patients will have received an indispensable service.

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