Tacrolimus-Lipid Suspension

Tacrolimus Lipid Suspension (Nanosomal Tacrolimus) is an immunosuppressant product consisting of lipid based Tacrolimus that is administered via intravenous injection. Tacrolimus Lipid Suspension is indicated for the prophylaxis of transplant rejection in liver, heart, and kidney allograft recipients. It is also indicated to the treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products.

Tacrolimus Lipid Suspension for injection is a sterile lyophilized powder supplied it glass vial. Each vial contains 5 mg Tacrolimus and is reconstituted by adding 4.5 mL of sterile water for injection to yield a preparation of 1 mg Tacrolimus/mL and further dilution is done with 5% dextrose injection, IP. Details of dosage and administration can be found in the package insert.

About Organ Transplantation

Organ transplantation has become an accepted medical treatment for end-stage organ failure. However, rejection of transplanted organs is the main barrier in transplantation. It occurs as a result of humoral and cell-mediated responses by the recipient to the specific antigens present in the donor tissue. The rejection can be either hyperacute rejection, acute rejection or chronic rejection. Allogeneic transplantation requires immunosupression for graft survival. In general, immunosuppressive therapy has both beneficial and detrimental effects on the transplant recipient. Tacrolimus is an immunosuppressant found to be effective, potent, and superior to cyclosporine and showed promising results in the reducing the risk of acute rejection in lung transplantation.

About Tacrolimus

Tacrolimus is a macrolide immunosuppressant produced by Stretomyces tsukubaensis and is used to prevent or reverse rejection in patients receiving organ transplants. Tacrolimus inhibits the formation of cytotoxic lymphocytes which are regarded as being primarily responsible for graft rejection. It binds to a cytosolic protein and the complex inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription. Because of poor water solubility, Tacrolimus is supplied in vehicles containing alcohol and polyoxyl 60 hydrogenated castor oil (HCO-60) for intravenous administration. However, toxicity of HCO-60 limits its maximal exploitation in clinical medicine. These toxic effects of HCO-60 include hypersensitivity reactions, allergic symptoms such as leukocytosis, hyperpyrexia, and immunological suppression of the growth of erythroid progenitors in humans. Treatments at high doses of HCO-60 based Tacrolimus have shown to cause neurotoxicity and nephrotoxicity.

Tacrolimus has an empirical formula of C44H69NO12.H2O and a formula weight of 822.03. It is practically insoluble in water, freely soluble in ethanol, and very soluble in chloroform and methanol. The structure of tacrolimus is shown below.

Why Tacrolimus Lipid Suspension

Tacrolimus Lipid Suspension is developed to reduce the hypersensitivity and other side effects associated with HCO-60 based Tacrolimus. Using Nanoaqualipâ„¢ technology [Link], Tacrolimus is formulated in aqueous media utilizing naturally occurring lipids. The lipids are non-toxic and safe in comparison to HCO-60. These lipid excipients used in Tacrolimus Lipid Suspension are naturally occurring and considered Generally Recognized as Safe (GRAS) by US FDA.

A comparative human pharmacokinetic and safety study with Tacrolimus Lipid Suspension and HCO-60 based Tacrolimus revealed similar biodistribution and clearance in the respective subjects. No significant difference in the volume of distribution, terminal half life, and total body clearance of Tacrolimus was observed when Tacrolimus Lipid Suspension and HCO-60 based Tacrolimus was administered intravenously. The clinical data suggests similar therapeutic benefits of Tacrolimus Lipid Suspension with HCO-60 based Tacrolimus with improved safety profile.

The advantages of Tacrolimus Lipid Suspension for injection includes

  • Proprietary Lipid Based Nanotechnology
  • No use of toxic solvents during the manufacturing process
  • Devoid of hypersensitivity reactions caused by polyoxyl 60 hydrogenated castor oil (HCO-60) used in HCO-60 based Tacrolimus for injection.
  • Similar pharmacokinetics profile as compared to HCO-60 based Tacrolimus for injection.
  • Low manufacturing cost.