Generic Maintenance Immunosuppression in Solid Organ Transplant Recipients

Abstract

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

The Cost of Transplant Immunosuppressant Therapy: Is This Sustainable?

“…Approval of generic therapies follows a different route for the FDA. Ensor et al provides an excellent overview of this approval process (6). Here, they concluded that generics are a reasonable option for transplant recipients but caution should be taken and education provided at the prescriber and patient level.…”

“…Other costs to consider include adverse effects, rejection episodes, etc. Immunosuppression was reported to account for approximately 6.6% of the total cost of renal transplantation in the first year and when considering 2010 AWP cyclosporine microemulsion, tacrolimus and mycophenolate generics are 15%, 7%, and 29% less expensive, respectively, than the branded products (6). …”

“…Moreover, one should take into consideration the cost and consequences of medication non-adherence (5). The introduction to the market of a number of generic formulations (mycophenolate mofetil (2008), tacrolimus (2009), mycophenolic sodium and sirolimus (both in 2014) has and will potentially continue to ease the financial burden, however, conversion concerns exist and even speculate increased initial costs in the short term due to laboratory monitoring (6). …”

Generics: Are all immunosuppression agents created equally?

“…[12][13][14][15][16][17] The same increased intrapatient variability was associated with poorer patient outcomes and greater treatment costs. A subsequent large retrospective study from the Collaborative Transplant Group showed that a group of 397 patients receiving generic cyclosporine had a trend toward overall poorer graft survival compared to the 17,198 patients receiving branded cyclosporine.…”

The Tyranny of Generic Immunosuppressants

“…These factors contribute to significant variability of many immunosuppressant medications even when using the same product. Therapeutic drug monitoring, early and often, is essential to maximize patient safety when product changes occur [4,5] .…”