Sublingual tacrolimus as an alternative to oral administration for solid organ transplant recipients

In this article, researched looked at available data to analyze sublingual tacrolimus and provide recommendations for solid organ transplant recipients.  Tacrolimus is an anti-rejection (immunosuppressant) medication that is available in many dosage forms but sublingual was analyzed in this study.

Typically, oral tacrolimus is used to prevent organ transplant rejection but due to it’s nature in a clinical setting many different situations occur that may prevent oral delivery.  For this reason, the researches wanted to explore the efficacy of a sublingual dosage form. The study found that about 50% of the oral dose needed to be delivered sublingually in order to get the targeted therapeutic effect.

Overall, the study helped to solidify the idea that sublingual dosing could be used as a short-term therapy for patient who cannot receive oral delivery.

Do you think that more drugs should be available sublingually? Especially ones used in a clinical setting?

Pennington CA, Jeong MP. Sublingual tacrolimus as an alternative to oral administration for solid organ transplant recipients.  Am J Health Syst Pharm.  2015;72(4):277-84.

Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids

Human islet transplantation is an experimental method for treating Type 1 Diabetes.  The islet cells are isolated from the donor’s pancreas, and once transplanted will hopefully begin to produce insulin in the recipient.  This study wanted to test some common immunosupressants–tacrolimus and sirolimus–and their effects on islet cells, which at this point are relatively undefined.  They also want to see what these immunosupressants would do when combined with each other and with a glucocorticoid, methylprednisilone.  All trials were done in vitro with human cells.

When tacrolimus alone was added to the islet cells, they did not decrease their ability to produce a basal rate of insulin, but did decrease their ability to respond acutely to a high concentration of glucose.  Sarolimus had no deleterious effects on the islet cells’ insulin production at all.  When the two immunosupressants were combined and added to the cells, they were no more harmful than the tacrolimus alone.  When the methylprednisilone was added, there was no decrease in the basal insulin rate, however, the stimulated secretion decreased after an hour in the glucose-dense solution.  Methylprednisolone did have another effect: it reduced the pro inflammatory abilities of the immunosupressants.  This trial will help pave the way for medication regimens for those receiving islet transplants in the future.

 

Kloster-Jensen K, Sahraoui A, Vethe NT, et al. Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids. J Diabetes Res. 2016;2016:1-9.

 

Stability of tacrolimus solutions in polyolefin containers

Tacrolimus is an immunosuppressant used for organ rejection prophylaxis in patients receiving liver, kidney, or heart transplantation. Tacrolimus is also indicated for prevention and treatment of graft-versus-host disease after hematopoietic stem cell transplantation. It is preferred via oral route of administration; however, an injectable solution can be administered via continuous infusion. The manufacturer recommends an expiration of 24 hours after preparation, so the combination of giving a drug by continuous infusion and a 24-hour expiration time may create challenges for some pharmacies.

Lee et al. conducted a study to determine the stability of tacrolimus solutions stored in polyolefin containers under various conditions. Triplicate solutions of tacrolimus (0.001, 0.01, and 0.1 mg/mL) in 0.9% sodium chloride injection or 5% dextrose injection were prepared in polyolefin containers. Some samples were stored at room temperature (20–25 °C); others were refrigerated (2–8 °C) for 20 hours and then stored at room temperature for up to 28 hours. The solutions stabilities were analyzed through high-performance liquid chromatography (HPLC) assay at various time points spanning 48 hours. The primary end point of this analysis was stability, defined as retaining greater than 90% of the initial tacrolimus concentration.

The results indicated that all samples, with the exception of the 0.001mg/mL sample solution prepared in 0.9% sodium chloride, had maintained greater than 90% of the initial concentration at all of the time points tested. The results suggest little to no loss of viable product to degradation or adsorption.  Lee et al. were able to show the stability of tacrolimus stored in polyolefin containers for at least 48 hours with the exception of the 0.001mg/mL sample solution prepared in 0.9% sodium chloride.

Am J Health-Syst Pharm. 2016;73(3):137-42.