Date of publication: May 16, 2014

News & Views

Adherence (Part 5) – Why do patients not adhere to phosphate binders: high pill burden?

Pill burden is recognized as a factor that can affect adherence in a number of diseases, such as HIV.[1] For dialysis patients, the daily pill intake is very high, with a large proportion of this burden comprised of phosphate binders.[2] Given that non-adherence to phosphate binders is common, is there evidence that shows a direct association between pill burden and adherence in dialysis patients?

Studies show that high pill burden affects adherence in phosphate binder treatment

In a cross-sectional study of 233 US dialysis patients, Chiu et al. found that 62% of patients were non-adherent and adherence decreased significantly with pill count.[2] The study results also suggested that low adherence could lead to over-prescription of phosphate binders and so to a greater pill burden. This clinical approach potentially creates a self-fulfilling, repeating cycle of low adherence, poor phosphorus control and dose escalation.


Importantly, overall pill burden was associated with a low physical component summary score of the SF-36 QoL (Quality of Life) assessment. Increasing the number of pills prescribed did not improve control of serum phosphorus levels and further reduced the patient’s quality of life assessment.[2]

Recently, Wang et al also found that increasing pill burden was associated with non-adherence, and non-adherence in turn was associated with poorly controlled serum phosphorus levels.[3] Using data from a pharmacy management program, the investigators tracked dialysis patients on phosphate binder monotherapy over time. 8,616 haemodialysis patient records were analysed, and their medication possession ratio (MPR) and pill burdens were calculated.

The Medication Possession Ratio is the proportion of days the patient has sufficient medication available to have taken the medication as prescribed. It is commonly used as an indirect measure of adherence, with a low MPR implying low adherence. An MPR of 100% would suggest perfect adherence.

The Wang et al. study found that:

  • Weighted MPR levels were low overall, ranging from 51% to 42% in different cohorts ,
  • MPR increased as pill burden decreased, with adherence strongest (51%) in the group with the lowest pill burden (0-3 pills per day), and
  • Higher MPR was associated with worse control of phosphorus to target ranges.

These results suggest that a lower pill burden results in greater adherence and lower phosphorus levels. The MPR levels of 40% to 50% align well with other real-world, medication adherence data, lending eight to this observational study.

While high pill burden is only one of several factors that may be contributing to poor adherence in dialysis patients, reducing this pill burden is a practical and achievable goal. Switching the type of binders used in patients to those which require less pills per day may deliver some of the improvements in adherence and outcomes that clinicians are seeking.

See also the previous Adherence articles:
March 24th, 2014; Adherence Part 1 – The challenge of non-adherence in hyperphosphatemia

April 11th, 2014; Adherence Part 2 – Is adherence to phosphate binder therapy associated with improved outcomes?

April 24th, 2014; Adherence Part 3 – Why do patients not adhere to therapies?

May 6th, 2014; Adherence Part 4 – Why do patients not adhere to phosphate binders:poor tolerability?


1. Nachega JB, Parienti J-J, Uthman OA, et al. Lower Pill Burden and Once-daily Dosing Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials. Clin Infect Dis Off Publ Infect Dis Soc Am. 2014. doi:10.1093/cid/ciu046.

2. Chiu Y-W, Teitelbaum I, Misra M, Leon EM de, Adzize T, Mehrotra R. Pill Burden, Adherence, Hyperphosphatemia, and Quality of Life in Maintenance Dialysis Patients. Clin J Am Soc Nephrol. 2009. doi:10.2215/CJN.00290109.

3. Wang S, Alfieri T, Ramakrishnan K, Braunhofer P, Newsome BA. Serum phosphorus levels and pill burden are inversely associated with adherence in patients on hemodialysis. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc – Eur Ren Assoc. 2013. doi:10.1093/ndt/gft280.

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