The Impact of Conversion From Prograf to Generic Tacrolimus in Liver and Kidney Transplant Recipients With Stable Graft Function.
Summary of "The Impact of Conversion From Prograf to Generic Tacrolimus in Liver and Kidney Transplant Recipients With Stable Graft Function."
Bioequivalence of the recently available generic tacrolimus formulation, manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma, Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in transplant patients have not been evaluated. Tacrolimus trough concentrations and indices of liver and kidney function were recorded before and after generic substitution in 48 liver and 55 kidney transplant recipients. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (±SD) was 184.1 (±123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (±87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D-ratios in kidney transplant patients were 125.3 (±92.7) and 110.4 (±79.2) ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p < 0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver and 0.87 ng/mL in kidney transplant patients following the switch, after accounting for all significant covariates. No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution. These results suggest that transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz-generic product provided trough concentrations are closely monitored following the substitution.
Affiliation
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA Center for Education and Drug Abuse Research, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA Department of Pharmacy and Therapeutics, School
Journal Details
This article was published in the following journal.
Name: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Tr
ISSN: 1600-6143
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21714845
- DOI: http://dx.doi.org/10.1111/j.1600-6143.2011.03615.x
Medical and Biotech [MESH] Definitions
Tacrolimus Binding Protein 1a
A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
Tacrolimus Binding Proteins
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
Hepatorenal Syndrome
Functional KIDNEY FAILURE in patients with liver disease, usually LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL), and in the absence of intrinsic renal disease or kidney abnormality. It is characterized by intense renal vasculature constriction, reduced renal blood flow, OLIGURIA, and sodium retention.
Tor Serine-threonine Kinases
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
Kidney Papillary Necrosis
A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.
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