Medication Non-Adherence Widespread

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Pediatric renal transplant patients often neglect to take their immunosuppressive drugs, data show.

PHILADELPHIA—Non-adherence to immunosuppressive medications is pervasive among pediatric patients who have undergone renal transplantation, a study found. Non-adherence begins as soon as four weeks following transplantation, and the problem increases as dosing regimens become more complex.

“What the study shows is that the drugs that we give patients for transplant are not taken as prescribed,” said investigator Thomas Nevins, MD, professor of pediatrics at the University of Minnesota Children's Hospital-Fairview in Minneapolis. Between 25% and 35% of patients who have a renal transplant will miss one or more doses of their medication each month, he said.

Quantitative data on post-transplant adherence to immunosuppressive regimens are scant. One recent meta-analysis of 46 studies suggested that non-adherence rates were approximately 22%. Renal transplant patients had the highest rates (35.6%), according to report in Transplantation (2007;83:858-873). For heart and liver transplant recipients, the percentages were 14.5% and 6.7%.

For this current study, electronic monitors in the medication vial caps were used to collect prospective dosing data on 195 pediatric renal transplant recipients beginning at initial hospital discharge. A total of 169 patients (87%) completed 12 months of monitoring. Medications that were monitored were azathioprine (AZA), mycophenolate mofetil (MMF), and sirolimus (SIR). Both AZA and SIR were usually prescribed as single daily doses; MMF was prescribed as twice daily.

Overall 12-month non-adherence, as expressed as days with fewer cap openings than doses prescribed, was 10.3%. Non-adherence began within four weeks after transplantation. Non-adherence rates were 14% at 1 month, 17% at three months, 15% at six months, and 16% at 12 months.  The researchers also identified a subgroup of 79 patients (40%) with sequentially declining adherence during the first 12 weeks of monitoring. Adherence rates differed significantly by medication. The percentage of non-adherence days was 19% for MMF, 7% for AZA, and 6% for SIR.

The number of doses prescribed on a daily basis also made difference. Regardless of the drug, the non-adherence rate was 7% if the drug was prescribed at once a day, 16% if prescribed twice daily, 27% if prescribed three times daily, and 44% if prescribed four times daily.

“Basically, the more complicated the regimen and the more doses each day, the more likely patients are to miss one or more of those doses,” said Dr. Nevins, who reported findings here at the American Society of Nephrology's Renal Week conference. “So, I think we need to do more when it comes to asking patients about their medications and when they are taking them. This seems like common sense but it is just not going on enough.”

Non-adherence is a leading cause of organ rejection among renal transplant patients, Dr. Nevins said. “If you could take care of this problem it would be every bit as important to the transplant community as the discovery of a new drug that has much better immunosuppressive properties,” he said.
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