Where Do You Put Tacrolimus?

Tacrolimus, a medication commonly known by its brand name Prograf, is primarily used to prevent rejection of organ transplants. It belongs to a class of drugs known as calcineurin inhibitors and works by suppressing the immune system. Proper application of tacrolimus is crucial to ensure its effectiveness and minimize side effects.Tacrolimus is a potent immunosuppressive agent used clinically to reduce the risk of graft rejection in post-operative transplants patients. It acts by suppressing interleukin-2 (IL-2) production in T-cells, and also by inhibiting phosphatase activity of calcineurin through binding to the intracellular immunophilin FKBP-12, The currently available intravenous formulation of TAC (Prograf) contains HCO-60 (PEGylated castor oil) as a surfactant, which is reported to cause several side effects including hypersensitivity reactions. TAC is available in oral dosage forms including immediate release capsules (Prograf), extended release capsules (Astagraf XL and Advagraf), and extended release tablets (Envarsus XR). Several adverse effects have been reported with the use of TAC including hypertension, pruritus, leucocytosis, neurotoxicity, nephrotoxicity, cardiotoxicity and hepatotoxicity

Application Areas

Tacrolimus is typically applied topically, meaning it is applied directly to the skin. It is commonly used to treat certain skin conditions, such as eczema (atopic dermatitis). When using tacrolimus powder, it is important to apply it only to the affected areas of the skin and to avoid applying it to areas that are not affected.Several formulations have been investigated to improve the aqueous solubility of TAC, enhance its efficacy, and reduce its toxicity. Polymeric nanoparticles (NPs) are a promising effective alternative to traditional drug formulations. Poly(lactic-co-glycolic acid) (PLGA) is a family of biodegradable copolymers that has been approved by the US FDA and European Medicine Agency (EMA) for biomedical applications. This polyester undergoes hydrolysis and the ultimate degradation products are lactic acid and glycolic acid, which are endogenous compounds and easily metabolized by the body via the Krebs cycle. The biocompatibility and safety profile of PLGA copolymers are well documented, and make them suitable carriers for drug delivery applications. Indeed, PLGA NPs have been successfully used for encapsulating various low and high molecular weight drugs and biologics. Encapsulation of drugs or macromolecules (e.g. peptides and proteins) into PLGA NPs have been shown to enhance the stability, control the release, and prolong the circulation time of the payload in the blood. Furthermore, PLGA NPs have also been shown to deliver antigens to dendritic cells. So far, the extensive research on the application of PLGA as drug delivery system have resulted in several marketed formulations (injectable implants) for human use.

Dosage and Frequency

The dosage and frequency of tacrolimus application can vary depending on the condition being treated and the formulation of the medication. It is important to follow the instructions provided by your healthcare provider or the medication label. Generally, tacrolimus powder is applied twice daily, unless otherwise directed by your healthcare provider.The whole blood was collected from four different treatment groups (Prograf, empty PLGA NP, tacrolimus-loaded PLGA NPs, and normal saline; n = 6 mice/group) was subjected to RBC lysis by the addition of RBC lysis solution before flow cytometric analysis. Animals (male mice) received the subcutaneous dose the similar way mentioned above in nephrotoxicity evaluation section except the duration was 7 days. Normal saline was used as a negative control. To assess in-vivo immunosuppressive effects of tacrolimus-loaded PLGA NPs, CD4⁺ and CD8⁺ T cells were analysed in whole blood using flow cytometry (LSRII BD biosciences). Peripheral blood mononuclear cells (PBMCs) were isolated from pooled whole blood samples of 5 mice (1.5 mL/mice) using Ficoll density gradient centrifugation. PBMCs were incubated with pre-warmed PBS containing carboxyfluorescein diacetate succinimidyl ester (CFSE) dye (2 μM) for 8 min at 37 °C. Thereafter, cells were washed with PBS and subsequently stimulated with Concanavalin A (ConA) super antigen (10 µg/mL/10⁶ cells). The cells were then incubated for 4 days at 37 °C. After incubation the cells were stained with fluorochrome conjugated anti CD4 or anti-CD8 antibodies specifically targeting T cells among the PBMCs. Standard surface staining protocol was followed for CD4⁺ and CD8⁺ T cells using anti-mouse CD4–APC (R&D systems) and CD8-PE-CY7 (R&D systems) monoclonal antibodies.

Application Technique

When applying tacrolimus powder, it is important to wash your hands before and after application. Use a thin layer of ointment and gently rub it into the affected area until it is absorbed. Avoid covering the treated area with bandages or dressings unless directed by your healthcare provider.Blood was collected from mice from all the treatment groups via cardiac puncture at the time of termination of the experiment. Serum was collected by centrifugation of whole blood at 1000 × g for 15 min. Levels of creatinine, urea, uric acid, and potassium were measured using standard diagnostic kits (Giesse Diagnostics, Rome, Italy). Blood was processed immediately after collection and all the parameters were measured on the same day. The same experiment was repeated in male and female Wistar rats (200–250 g).

Precautions

It is important to avoid exposure to sunlight or tanning beds while using tacrolimus, as it can increase the risk of sunburn. If you need to be outdoors, wear protective clothing and use sunscreen. Additionally, avoid getting tacrolimus powder in your eyes, nose, or mouth. If contact occurs, rinse thoroughly with water.

Side Effects

Common side effects of tacrolimus powder include stinging, burning, or itching at the application site. These side effects are usually mild and temporary. However, if you experience severe or persistent side effects, contact your healthcare provider.

Conclusion

Proper application of tacrolimus is essential for its effectiveness and safety. By following the instructions provided by your healthcare provider and the medication label, you can help ensure that you get the most benefit from tacrolimus while minimizing the risk of side effects. If you have any questions or concerns about using tacrolimus, talk to your healthcare provider.

For more information about Tacrolimus, please contact Emily at emily@jiubaiyuanbiotech.com.

References

1. Wallemacq, P., et al. (2009). "Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant patients: Impact of comedication and effect of renal dysfunction." *Clinical Pharmacokinetics*, 48(2), 141-153.

2. Lemaire, M., et al. (1999). "Recent clinical experience with tacrolimus in adult kidney transplantation." *Transplantation Proceedings*, 31(1-2), 51S-53S.

3. Hocker, B., et al. (2010). "Comparison of the efficacy and safety of tacrolimus versus cyclosporine in kidney transplantation: A meta-analysis of randomized trials." *American Journal of Transplantation*, 10(7), 1356-1362.

4. Murphy, K. J., et al. (2015). "Tacrolimus pharmacokinetics and dosing in obese kidney transplant recipients." *Clinical Pharmacokinetics*, 54(6), 629-640.

5. Thervet, E., et al. (2010). "Optimal use of tacrolimus in kidney transplantation." *Transplant International*, 23(6), 649-659.

6. Shapiro, R., et al. (2002). "A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/mycophenolate mofetil/prednisone in renal transplantation." *Transplantation*, 73(12), 1775-1782.