Generics: Are all immunosuppression agents created equally?

Hauch, Adam; John, Mira; Smith, Alison; Dortonne, Isabelle; Patel, Ushma; Kandil, Emad; Killackey, Mary; Paramesh, Anil; Lee, Belinda; Zhang, Rubin; Buell, Joseph F.

doi:10.1016/j.surg.2015.05.024

Cited by 12 publications

(13 citation statements)

References 19 publications

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“…). Only one study after KT conversion found a significant difference between generic and innovator Tac favoring innovator Tac , while one in KT de novo found a significant benefit of generic Tac . Two further crossover studies including 103 patients after KT and 36 patients after LT conversion did not report any BPAR event.…”

Section: Resultsmentioning

confidence: 95%

“…Furthermore, there were 2 (4.3%) versus no graft losses reported with de novo innovator Tac after LT . More drug level variability and dose adjustments necessary during the first weeks after transplantation in de novo use and also after conversion was reported .…”

Section: Resultsmentioning

confidence: 99%

“…A total of 390 publications were excluded during abstract screening. After the elimination of preliminary reports (2), case reports (3), reviews (25), and studies without a control group (16), 17 studies met the inclusion criteria (Fig. ).…”

Section: Resultsmentioning

confidence: 99%

“…One de novo study with generic Tac evaluated cost‐effectiveness and reported cost savings within the first 14 days . One conversion study indicated higher costs with generic Tac due to monitoring and hospitalization , whereas one conference abstract confirmed cost‐effectiveness.…”

Section: Resultsmentioning

confidence: 99%

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Immunosuppression with generic tacrolimus in liver and kidney transplantation—systematic review and meta‐analysis on biopsy‐proven acute rejection and bioequivalence

2020

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Summary While rejection prevention with innovator tacrolimus (Tac) is one of the key factors for long‐lasting graft function, the use of generic Tac is still under debate. Thus, we performed a systematic review and meta‐analysis to provide an overview on the current body of evidence for the effect of generic Tac in adult liver (LT) and kidney transplantation (KT) with focus on both biopsy‐proven acute rejection (BPAR) and bioequivalence. A systematic literature search for trials comparing generic versus innovator Tac was conducted accordingly. Seventeen studies (5 LT, 11 KT, 1 LT/KT) including 1412 patients were identified. About 92.9% (13/14; 5/5 LT, 8/9 KT) of studies reported the same or lower BPAR with generics (pooled RR: 0.84, 95% CI: 0.65–1.09); however, de novo studies showed a significantly lower risk with generic Tac (RR: 0.75, 95% CI: 0.63–0.90), whereas conversion studies showed increased risk (RR: 1.93, 95% CI: 1.00–3.70). Bioequivalence was demonstrated primarily in studies on conversion. The current evidence is mostly based on observational data and studies showing some risk of bias. In conclusion, whereas overall there was no significant difference in terms of BPAR, there is some evidence suggesting lower BPAR risk with generic Tac for de novo use.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Immunosuppression with generic tacrolimus in liver and kidney transplantation—systematic review and meta‐analysis on biopsy‐proven acute rejection and bioequivalence

2020

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“…24 Tacrolimus and mycophenolate are off patent, and so cheaper generic formulations are now recommended, but uncontrolled switching between generics should be avoided as it may result in hazardous variation in blood drug levels. 25 Some transplant units withdraw steroids in the first few weeks after transplantation. 26 Ciclosporin and azathioprine are still used in selected recent transplant recipients and in many who were transplanted more than 10 years ago.…”

Section: Immunosuppressionmentioning

confidence: 99%

Renal transplantation in adults

Nieto

Inston

Cockwell

2016

BMJ

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Evaluation of Clinical and Safety Outcomes Following Uncontrolled Tacrolimus Conversion in Adult Transplant Recipients

et al. 2019

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PURPOSE To compare clinical and safety outcomes of transplant recipients converted between different tacrolimus formulations to those patients who remained on a single formulation in an outpatient environment. METHODOLOGY This was a single-center, retrospective cohort study at a large tertiary care medical center with an associated institutional outpatient pharmacy system. Adult transplant recipients with institutional pharmacy refill from August 1, 2009, to May 31, 2016, were assessed. Patients were allocated into four separate groups: Group (A) innovator tacrolimus (no conversion), Group (B) generic tacrolimus (no conversion), Group (C) single conversion (from innovator to single generic or from generic to innovator tacrolimus), and Group (D) multiple conversions. Index date was either the date of first tacrolimus product conversion (Groups C and D) or a pre-specified posttransplant time (Groups A and B). RESULTS Overall, 100 patients were included in the analysis, 63% were male, 62% were Caucasian, and 59% were renal transplant recipients. When compared between groups, linear trends in dose-normalized tacrolimus levels were similar in the pre-index date period (p=0.52) and in the post-index date period (p=0.08). When groups were compared individually, linear trends in dose-normalized tacrolimus levels were significantly different pre-versus post-index date for Group B (p=0.008). There were no differences in the linear trends of dose-normalized tacrolimus levels across the other groups (p>0.05 for all). After the index date, 43% of patients across all groups required tacrolimus dose modification with no differences by group (p=0.32). Allograft function and hospitalizations were similar across all groups.CONCLUSIONS Conversion between tacrolimus generic formulations has been suggested to be unsafe. This study demonstrates that switching tacrolimus products in post-transplant recipients does not alter dose-normalized tacrolimus trough concentrations, renal or hepatic function, pathology, or hospitalizations.

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Generics: Are all immunosuppression agents created equally?

Cited by 12 publications

References 19 publications

Immunosuppression with generic tacrolimus in liver and kidney transplantation—systematic review and meta‐analysis on biopsy‐proven acute rejection and bioequivalence

Immunosuppression with generic tacrolimus in liver and kidney transplantation—systematic review and meta‐analysis on biopsy‐proven acute rejection and bioequivalence

Renal transplantation in adults

Evaluation of Clinical and Safety Outcomes Following Uncontrolled Tacrolimus Conversion in Adult Transplant Recipients

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