Generics: are all immunosuppression agents created equally?

Abstract

Background: The Affordable Care Act initiated innumerable cost-containment measures, including promoting generic conversion from brand medications and directing the Food and Drug Administration to decrease requirements for generic approvals. Despite this mandate, few data existed on generic conversion of immunosuppressant medications with narrow therapeutic troughs.

Methods: A retrospective analysis of our initial experience with generic tacrolimus (n = 39) was performed using a control cohort from our renal transplant database. A rejection and cost analysis was performed using a consecutive 2-year prior cohort (n = 159) as a control to determine the effect of generic conversion on tacrolimus a narrow therapeutic index immunosuppressant medication.

Results: During the first year after transplantation, the generic group had a greater drug variability (20% ± change in trough levels) that required more dosage adjustments (5.42 vs 3.59 drug dosage changes; P = .038) to obtain a stable dose, required increased number of intravenous magnesium infusions (4.95 vs 1.68 infusions; P = .001), and incurred a greater incidence of rejection (23.1% vs 10.2%; P = .024). A yearly institutional cost was evaluated against a negotiated $18,000/yearly central pharmacy cost savings compared with a $652,862 institutional cost to treat unanticipated rejections.

Conclusion: Programmatic conversion from brand to generic tacrolimus resulted in increased drug variability, a greater incidence of magnesium wasting, and more episodes of rejection, leading to increases in institutional costs of care. This government-driven attempt at cost containment may be applicable to noncritical medications such as antibiotics and antihypertensives, but this policy should be reconsidered for narrow therapeutic index medications, such as tacrolimus and other immunosuppressant medications.