title: Use of generic tacrolimus in elderly renal transplant recipients: precaution is needed.
abstract: BACKGROUND
  Proper bioequivalence studies comparing original with generic immunosuppressive drugs in patients are limited, especially in the increasing population of elderly renal transplant recipients. We performed an open-label, single-center, prospective, randomized, cross-over study and compared steady-state pharmacokinetics (PK) of a generic tacrolimus (Tacni) formulation with the original (Prograf) in renal transplant recipients older than 60 years.
  
  
  METHODS
  Twenty-eight patients, with a median age of 69 years (range, 60 to 78), were randomized at time of transplantation to receive original or generic tacrolimus, and 25 (21 men, 4 women) provided two evaluable 12-hr PK profiles. The PK investigations were performed in a stable phase approximately 6 and 8 weeks postengraftment. After the first PK investigation, tacrolimus formulations were switched (1:1 dose ratio).
  
  
  RESULTS
  Generic tacrolimus did not meet the bioequivalence criteria; the area under the curve(0-12) ratio of generic-original tacrolimus formulation was 1.17 (90% confidence interval, 1.10-1.23) and the Cmax ratio was 1.49 (90% confidence interval, 1.35-1.65). The generic formulation also showed a shorter time to C(max) (T(max)) (P=0.04). Importantly, the lack of bioequivalence was not reflected in the standard monitoring parameter, trough concentrations (P=0.80).
  
  
  CONCLUSIONS
  Generic tacrolimus (Tacni) was not found to be bioequivalent to the original formulation in elderly renal transplant recipients. The significantly higher systemic exposure of tacrolimus, despite similar trough concentrations, may in the long run increase the risk of adverse effects.
authors.affiliation: 1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. 2 Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 3 Department of Pharmacology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 4 Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Ida
authors.initials: I
authors.lastname: Robertsen
authors.forename: Anders
authors.initials: A
authors.lastname: Åsberg
authors.forename: Aleksander Olsen
authors.initials: AO
authors.lastname: Ingerø
authors.forename: Nils Tore
authors.initials: NT
authors.lastname: Vethe
authors.forename: Sara
authors.initials: S
authors.lastname: Bremer
authors.forename: Stein
authors.initials: S
authors.lastname: Bergan
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
mesh_terms: D000368:Aged; D019540:Area Under Curve; D018592:Cross-Over Studies; D016568:Drugs, Generic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000601:surgery*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D013810:Therapeutic Equivalency; D066027:Transplant Recipients
chemical_list: D016568:Drugs, Generic; D007166:Immunosuppressive Agents; D016559:Tacrolimus